Application of sodium octanoate in the preparation of drugs for treating sepsis

Abstract

The present invention provides an application of sodium octanoate in the preparation of a drug for treating sepsis, and relates to the technical field of pharmaceutical preparations. The present application has been studied and found that sodium octanoate can effectively inhibit the inflammatory storm induced by sepsis, alleviate sepsis-induced multiple organ dysfunction and prolong the survival period of sepsis when the body undergoes complex pathological and physiological changes during sepsis. This provides a new medical means for the treatment of clinical sepsis patients, which has great research significance and application prospects.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, and in particular to application of sodium octanoate in the preparation of a drug for treating sepsis. Background Art

[0002] Sepsis is a life-threatening multi-organ dysfunction syndrome caused by a dysregulated response to infection that kills millions of people each year. Traditionally, sepsis has been viewed as an inflammatory disease.

[0003] However, there is increasing evidence that metabolic homeostasis abnormalities play an important role in the pathogenesis of sepsis. Typical clinical manifestations of sepsis include high fever, tachycardia, tachypnea, inflammation, immune activation, and acute phase reactions. In addition, chemical mediators such as endotoxins, cytokines, and nitric oxide, as well as systemic inflammatory responses, can impair the ability of cardiac cells to produce ATP, impair cardiac energy metabolism, and lead to cardiac dysfunction. At the same time, complex pathophysiological changes occur in the body during sepsis, which can also lead to severe liver and kidney dysfunction.

[0004] Therefore, it is necessary and urgent to develop a drug that can effectively treat sepsis to inhibit the sepsis-induced inflammatory storm, alleviate sepsis-induced multiple organ dysfunction and prolong the survival period of sepsis.

[0005] In view of this, the present invention is proposed. Summary of the invention

[0006] The purpose of the present invention is to provide a drug for treating sepsis, wherein the functional component of the drug is sodium octanoate. Experimental verification shows that sodium octanoate can effectively inhibit the inflammatory storm induced by sepsis, alleviate the multiple organ dysfunction induced by sepsis and prolong the survival period of sepsis.

[0007] In order to achieve the above-mentioned purpose of the present invention, the following technical solutions are particularly adopted:

[0008] The invention provides an application of sodium octanoate in preparing a drug for treating sepsis.

[0009] Furthermore, the application includes:

[0010] (A) Inhibit sepsis-induced inflammatory storm;

[0011] (B) Alleviate sepsis-induced multiple organ dysfunction;

[0012] (C) Prolong survival in sepsis.

[0013] Furthermore, the sepsis-induced inflammatory storm includes: high expression of inflammatory factors TNF-α, IL-1β and IL-6 in plasma under sepsis state.

[0014] Furthermore, the sepsis-induced multiple organ dysfunction includes: cardiac dysfunction, liver dysfunction and renal dysfunction.

[0015] The present invention provides a medicine for treating sepsis, which comprises sodium octanoate and pharmaceutically acceptable excipients.

[0016] Furthermore, the pharmaceutically acceptable excipients include one or more of a diluent, a binder, a wetting agent, a disintegrant, a lubricant, a solubilizer, a pH regulator and an osmotic pressure regulator.

[0017] Furthermore, the dosage form of the drug is an injection.

[0018] Furthermore, the administration route of the injection includes one of intravenous injection, intraperitoneal injection, intramuscular injection or subcutaneous injection.

[0019] Furthermore, the injection is administered via intraperitoneal injection, and the dosage of the intraperitoneal injection is 160 mg / kg.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] The application of sodium octanoate provided by the present invention in the preparation of a drug for treating sepsis. Experimental verification shows that sodium octanoate can effectively inhibit the inflammatory storm induced by sepsis, alleviate the multiple organ dysfunction induced by sepsis and prolong the survival period of sepsis, providing a new medical means for the treatment of clinical sepsis patients, and has great research significance and application prospects.

[0022] The drug for treating sepsis provided by the present invention comprises sodium octanoate and pharmaceutically acceptable excipients. The sodium octanoate in the drug can effectively alleviate the inflammatory storm and multiple organ dysfunction induced by sepsis, and prolong the survival period of sepsis. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0024] Figure 1 Representative echocardiographic images of sodium caprylate improving myocardial contractile function in LPS-induced septic mice provided in Example 2 of the present invention;

[0025] Figure 2Representative echocardiographic images of sodium octanoate improving myocardial contractile function in CLP septic mice provided in Example 2 of the present invention;

[0026] Figure 3 A graph showing the levels of acetyl-CoA in the heart and plasma of septic mice after treatment with sodium octanoate provided in Example 2 of the present invention;

[0027] Figure 4 A violin plot of differential metabolite expression levels in the hearts of mice in the LPS+SO group and the LPS group after sodium octanoate intervention provided in Example 2 of the present invention;

[0028] Figure 5 This is a graph showing the effect of sodium caprylate on the levels of plasma inflammatory factors in LPS-induced septic mice detected by ELISA provided in Example 2 of the present invention;

[0029] Figure 6 This is a graph showing the effect of sodium octanoate on the expression levels of cardiac inflammatory factors in LPS-induced septic mice detected by qPCR provided in Example 2 of the present invention;

[0030] Figure 7 This is a graph showing the effect of sodium caprylate on the expression levels of cardiac inflammatory factors in CLP-induced septic mice detected by qPCR provided in Example 2 of the present invention;

[0031] Figure 8 This is a graph showing the effect of sodium octanoate on the levels of plasma myocardial injury markers in LPS-induced septic mice provided in Example 2 of the present invention;

[0032] Fig. 9 This is a graph showing the blood biochemical test results of LPS-induced sepsis mice after treatment with sodium caprylate provided in Example 2 of the present invention;

[0033] Fig.10 This is a diagram of pathological changes in heart tissue of LPS-induced septic mice evaluated by HE staining after sodium caprylate treatment provided in Example 2 of the present invention;

[0034] Fig.11 A representative image of DHE staining of mouse heart frozen sections after LPS injection and sodium octanoate treatment provided in Example 2 of the present invention;

[0035] Fig.12 This is a graph showing the effect of sodium caprylate on the survival rate of septic mice provided in Example 2 of the present invention. DETAILED DESCRIPTION

[0036] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0037] According to one aspect of the present invention, a use of sodium caprylate in the preparation of a drug for treating sepsis.

[0038] The application of sodium octanoate provided by the present invention in the preparation of a drug for treating sepsis. Experimental verification shows that sodium octanoate can effectively inhibit the inflammatory storm induced by sepsis, alleviate the multiple organ dysfunction induced by sepsis and prolong the survival period of sepsis, providing a new and important medical means for the treatment of clinical sepsis patients, and has great research significance and application prospects.

[0039] In a preferred embodiment of the present invention, the application comprises:

[0040] (A) Inhibit sepsis-induced inflammatory storm;

[0041] (B) Alleviate sepsis-induced multiple organ dysfunction;

[0042] (C) Prolong survival in sepsis.

[0043] It should be noted that during the onset of symptoms, the body of sepsis patients undergoes complex pathophysiological changes. In the case of complex pathophysiological changes in the body of sepsis, chemical mediators such as endotoxins, cytokines and nitric oxide, as well as systemic inflammatory responses, can impair the ability of cardiac cells to produce ATP, impair cardiac energy metabolism and lead to cardiac dysfunction. For example, patients with severe sepsis and septic shock often experience impaired myocardial contractility, a phenomenon known as sepsis-induced myocardial dysfunction (SIMD). SIMD usually manifests as acute systemic heart failure and decreased cardiac contractility. The mechanisms of SIMD include inflammatory factor storm, release of myocardial inhibitory factors, oxidative stress and mitochondrial dysfunction.

[0044] In the above preferred embodiment, the sepsis-induced inflammatory storm includes: high expression of inflammatory factors TNF-α, IL-1β and IL-6 in plasma under sepsis state.

[0045] In the above preferred embodiment, the sepsis-induced multiple organ dysfunction includes: cardiac dysfunction, liver dysfunction and renal dysfunction.

[0046] According to one aspect of the present invention, a drug for treating sepsis comprises sodium caprylate and pharmaceutically acceptable excipients.

[0047] The drug for treating sepsis provided by the present invention comprises sodium octanoate and pharmaceutically acceptable excipients. The sodium octanoate in the drug can effectively alleviate the inflammatory storm and multiple organ dysfunction induced by sepsis, and prolong the survival period of sepsis.

[0048] In a preferred embodiment of the present invention, the pharmaceutically acceptable excipients include one or more of a diluent, a binder, a wetting agent, a disintegrant, a lubricant, a solubilizer, a pH regulator and an osmotic pressure regulator.

[0049] In a preferred embodiment of the present invention, the dosage form of the drug is an injection.

[0050] In the above preferred embodiment, the administration route of the injection includes one of intravenous injection, intraperitoneal injection, intramuscular injection or subcutaneous injection.

[0051] In a preferred embodiment of the present invention, the injection is administered via intraperitoneal injection, and the dosage of the intraperitoneal injection is 160 mg / kg.

[0052] The technical solution of the present invention will be further described below in conjunction with embodiments.

[0053] Example 1

[0054] 1. Establishment of experimental animal model:

[0055] Male C57BL / 6 mice aged 8 weeks and weighing between 20-25g were used to establish a sepsis model by cecal ligation and puncture (CLP) surgery and intraperitoneal injection of LPS (lipopolysaccharide). The specific modeling method is as follows:

[0056] CLP model: After anesthetizing the mice, fix them in the supine position, shave the abdomen and disinfect it, make a surgical incision of about 2 cm in the middle of the abdomen and open the abdominal cavity to expose the cecum, expose its distal end and the mesentery of the large intestine, and ligate the cecum at the distal 1 / 2 of the cecum with sterile 4-0 silk thread to cause local ischemia of the cecum. Use a sterile 18-gauge needle to puncture the ligated cecum twice, gently squeeze out a small amount of intestinal contents, carefully put the cecum back into the abdominal cavity, suture the incision with sterile 4-0 silk thread, and close the abdominal cavity. Immediately after surgery, give the mice a subcutaneous injection of 1 mL of normal saline, place them on a constant temperature blanket for recovery, and keep them warm and quiet.

[0057] LPS model: LPS (lipopolysaccharide) was injected intraperitoneally into mice at a dose of 20 mg / kg.

[0058] 2. Animal randomization and intervention:

[0059] (II.1) LPS model mice were randomly divided into four groups:

[0060] Mice were intraperitoneally injected with phosphate buffered saline (PBS) as the control group (Control group, n=7);

[0061] Intraperitoneal injection of LPS was used as the model group (LPS group, n=7):

[0062] Sodium octanoate Q2h treatment group (LPS+SO Q2h group, n=7);

[0063] Sodium octanoate Q4h treatment group (LPS+SO Q4h group, n=7);

[0064] Among them, mice in the LPS group, LPS+SO Q2h and LPS+SO Q4h groups were intraperitoneally injected with 20 mg / kg LPS to induce sepsis model.

[0065] The mice in the control group were intraperitoneally injected with an equal amount of PBS.

[0066] In the LPS+SO Q2h group and the LPS+SO Q4h group, after intraperitoneal injection of LPS, sodium octanoate was administered within 30 minutes at a dose of 160 mg / kg, and then the administration was repeated every 2 hours and 4 hours, for a total of 6 and 3 times, respectively. At the same time as sodium octanoate administration, the mice in the LPS group were given an equal amount of normal saline. Finally, 12 hours after LPS injection, cardiac ultrasound was performed on the mice in each group, and then the mice were euthanized, and the heart and whole blood were quickly obtained for subsequent testing.

[0067] (II.2) The CLP-induced mouse sepsis model was randomly divided into three groups:

[0068] Sham operation control group (sham group, n=6);

[0069] CLP modeling group (CLP group, n=6);

[0070] Sodium caprylate treatment group (CLP+SO, n=6).

[0071] Mice in the sham group underwent abdominal wall incision and suturing, but no ligation or puncture was performed.

[0072] The mice in the CLP group underwent cecal ligation and puncture surgery to establish the model. The mice in the CLP+SO group were given sodium octanoate at a dose of 160 mg / kg within 30 minutes after model establishment, and then the administration was repeated every 8 hours. Finally, 24 hours after the CLP surgery, cardiac ultrasound was used to detect the cardiac function of mice in each group, and then the mice were euthanized, and the heart and whole blood were quickly obtained for subsequent testing.

[0073] Example 2

[0074] 1. Mouse cardiac function test:

[0075] Before administration (baseline) and 12 hours after administration of each group of LPS model mice in Example 1 (II.1), and before modeling and 24 hours after modeling of each group of CLP model mice in Example 1 (II.2), the mice were subjected to echocardiography using the Vevo2100 imaging system to evaluate cardiac function and record the respiration and heart rate of the mice. The left ventricular end-systolic volume and left ventricular end-diastolic volume, left ventricular end-diastolic diameter and left ventricular end-systolic diameter were measured. At the same time, the left ventricular ejection fraction and left ventricular shortening fraction were calculated by formulas, respectively.

[0076] The test results are as follows:

[0077] 1. Changes in myocardial contractile function of each group of animals refer to Figure 1 and Figure 2 .

[0078] Figure 1 Representative echocardiographic images of sodium caprylate improving myocardial contractile function in LPS-induced septic mice provided in this example.

[0079] in: Figure 1 (A) shows representative echocardiographic images of mice in each group 12 h after LPS injection. Figure 1 Middle (B) is a graph showing the statistical results of the ejection fraction EF% and shortening fraction FS% calculated by echocardiography of mice in each group. Figure 1 (B) n = 6. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. P < 0.05 was considered to be statistically significant.

[0080] Figure 2 Representative echocardiographic images of sodium caprylate improving myocardial contractile function in CLP septic mice provided in this example.

[0081] in, Figure 2 Middle (A) shows representative echocardiographic images of mice in each group 24 h after CLP modeling. Figure 2Middle (B) shows the calculation and statistics of the ejection fraction EF% and shortening fraction FS% of mice in each group through echocardiography. Figure 2 In (B), n=6. * P<0.05, ** P<0.01, *** P<0.001, **** P<0.0001. P<0.05 was considered statistically significant.

[0082] See also Figure 1 , Figure 2 It can be seen that 12 hours after LPS injection, the cardiac function of mice was detected by echocardiography. The results showed that compared with the mice in the Control group, the mice in the LPS group had severe myocardial systolic dysfunction, as manifested by a significant decrease in ejection fraction EF% and shortening fraction FS%. Therefore, sodium octanoate treatment effectively improved the myocardial systolic dysfunction caused by LPS. In the CLP model, compared with the mice in the CLP group, the myocardial systolic function of the mice in the CLP+SO group was also improved.

[0083] (II) Detection of acetyl-CoA concentration in plasma and heart of septic mice:

[0084] 12 hours after injection of each experimental group of LPS model mice, blood was collected from the right ventricle of the mice, and the heart was quickly removed. The tissue was rinsed with pre-cooled PBS to remove residual blood, and stored in liquid nitrogen. After the myocardial tissue was homogenized, the protein concentration was detected by BCA.

[0085] Then, follow-up tests were performed according to the instructions of the acetyl coenzyme A (A-CoA) enzyme-linked immunosorbent assay kit (Elabscience). At the same time, part of the heart tissue was taken for energy metabolomics testing to quantitatively detect the content of energy substances such as acetyl coenzyme A in myocardial tissue.

[0086] The results of heart and plasma acetyl-CoA test in each group of animals are as follows: Figure 3 , Figure 5 shown.

[0087] Figure 3 A graph showing the levels of acetyl-CoA in the heart and plasma of septic mice after sodium caprylate treatment is provided for this example. Figure 3 Middle (A) is the ELISA method to detect the plasma acetyl-CoA content of mice after LPS injection and sodium octanoate treatment, n = 7; Figure 3 Middle (B) Acetyl-CoA content was detected by mouse cardiac metabolomics after LPS injection and sodium octanoate treatment. Figure 3 n = 4. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. P < 0.05 was considered to be statistically significant between the groups.

[0088] Depend on Figure 3 It can be seen that compared with the mice in the LPS group, the levels of acetyl-CoA in the plasma and heart of the mice in the LPS+SO group were significantly increased.

[0089] Figure 4 This is a violin plot of the differential metabolite expression levels in the hearts of mice in the LPS+SO group and the LPS group after sodium caprylate intervention provided in this example. Figure 4 The horizontal axis is the group, and the vertical axis is the expression level. n=4. Glutamine, L-Leucine, L-citrulline, L-Asparagine, Arginine, Acetyl-CoA.

[0090] Depend on Figure 4 The results of cardiac energy metabolomics tests of each group of animals showed that 6 significantly different metabolites were screened out by comparing the mice in the LPS+SO group and the LPS group, of which 5 metabolites were upregulated (including acetyl-CoA, L-asparagine, arginine, L-citrulline, and glutamine), and one metabolite was downregulated (leucine).

[0091] (III) Detection of plasma inflammatory factors, myocardial injury markers, and liver and kidney function indicators in septic mice. The specific methods are as follows:

[0092] 12 hours after LPS injection, blood was collected from the right ventricle of the mice, and then centrifuged at 400g for 20 minutes at 4°C to separate the plasma. Then, ELISA kits were used to detect mouse tumor necrosis factor-α (TNF-α), mouse interleukin-6 (IL-6), mouse interleukin-1β (IL-1β), mouse lactate dehydrogenase (LDH), mouse cardiac creatine kinase isoenzyme MB (CK-MB), and mouse cardiac troponin I (cTnI). At the same time, liver and kidney function injury indicators such as ALT, AST, SCr, and BUN in mouse serum were detected.

[0093] The specific experimental results are as follows:

[0094] 1. Changes in the expression levels of plasma inflammatory factors and cardiac inflammatory factors in each group of animals:

[0095] Figure 5 This example provides a graph showing the effect of sodium caprylate on the levels of plasma inflammatory factors in LPS-induced septic mice as detected by ELISA.

[0096] in, Figure 5 Middle (A) is a graph showing the level of TNF-α inflammatory factor in the plasma of LPS-induced sepsis mice after treatment with sodium caprylate using ELISA; Figure 5 Middle (B) is a graph showing the level of IL-1β inflammatory factor in the plasma of LPS-induced sepsis mice after treatment with sodium caprylate using ELISA; Figure 5 Middle (C) is a graph showing the level of IL-6 inflammatory factor in the plasma of LPS-induced sepsis mice after treatment with sodium caprylate detected by ELISA. Figure 5 n=7. * P<0.05, ** P<0.01, *** P<0.001, ****P<0.0001. P<0.05 was considered statistically significant.

[0097] Depend on Figure 5 It can be seen that the results of plasma inflammatory factors detection in each group of animals show that compared with the control group of mice, the plasma TNF-α, IL-1β, and IL-6 in the LPS group mice were significantly increased. Compared with the LPS group, the levels of the three inflammatory factors in the sodium octanoate Q4h treatment group were significantly reduced.

[0098] Figure 6 This example provides a graph showing the effect of sodium caprylate on the expression levels of cardiac inflammatory factors in LPS-induced septic mice detected by qPCR.

[0099] in, Figure 6 Middle (A) is the mRNA expression level of TNF-α, a cardiac inflammatory factor in LPS-induced septic mice after treatment with sodium caprylate, detected by qPCR; Figure 6 Middle (B) is the detection of the mRNA expression level of IL-Iβ, a cardiac inflammatory factor, in LPS-induced sepsis mice after sodium caprylate treatment by qPCR; Figure 6 Middle (C) The mRNA expression level of IL-6, a cardiac inflammatory factor in LPS-induced sepsis mice, was detected by qPCR after treatment with sodium caprylate. Figure 6 n=7. * P<0.05, ** P<0.01, *** P<0.001, **** P<0.0001. P<0.05 was considered statistically significant.

[0100] Figure 7 This example provides a graph showing the effect of sodium caprylate on the expression levels of cardiac inflammatory factors in CLP-induced septic mice detected by qPCR.

[0101] in, Figure 7Middle (A) is the mRNA expression level of cardiac inflammatory factors TNF-α and in CLP-induced septic mice after sodium caprylate treatment detected by qPCR; Figure 7 Middle (B) is the detection of the mRNA expression level of IL-1β, a cardiac inflammatory factor, in CLP-induced septic mice after sodium octanoate treatment by qPCR; Figure 7 Middle (C) shows the mRNA expression level of IL-6, a cardiac inflammatory factor in CLP-induced septic mice after treatment with sodium caprylate, detected by qPCR. Figure 7 n = 5. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001.

[0102] Depend on Figure 6 , Figure 7 The results of the expression of inflammatory factors in the hearts of animals in each group showed that compared with the mice in the Control group, the expression levels of inflammatory factors TNF-α, IL-1β and IL-6 in the hearts of mice in the LPS group were all significantly increased, while compared with the LPS group, the expression levels of TNF-α and IL-1β in the hearts of mice in the sodium octanoate Q4h treatment group were significantly decreased. In the CLP model, compared with the mice in the sham group, the mRNA expression levels of inflammatory factors TNF-α, IL-Iβ and IL-6 in the hearts of mice in the CLP group were significantly increased. Compared with the mice in the CLP group, the expression levels of TNF-α, IL-1β and IL-6 in the hearts of mice in the CLP+SO group were significantly decreased.

[0103] 2. Detection results of cardiac injury markers in each group of animals.

[0104] Figure 8 This example provides a graph showing the effect of sodium caprylate on the levels of plasma myocardial injury markers in LPS-induced septic mice.

[0105] in, Figure 8 Middle (A) is a graph showing the level of myocardial injury marker CK-MB in the plasma of LPS-induced sepsis mice after treatment with sodium caprylate detected by ELISA; Figure 8 Middle (B) is a graph showing the level of myocardial injury marker cTnI in the plasma of LPS-induced sepsis mice after treatment with sodium caprylate detected by ELISA; Figure 8 Middle (C) is a graph showing the level of myocardial injury marker LDH in the plasma of LPS-induced sepsis mice after treatment with sodium caprylate detected by ELISA. Figure 8 n = 7. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. P < 0.05 was considered to be statistically significant between the groups.

[0106] Depend on Figure 8It can be seen that compared with the Control, the levels of cTnI, CK-MB and LDH in the plasma of mice in the LPS group were significantly increased. Compared with the LPS group, the levels of cTnI, CK-MB and LDH in the plasma of mice in the sodium octanoate Q4h treatment group were significantly decreased, while the cTnI level in the plasma of mice in the sodium octanoate Q2h treatment group was significantly decreased, and the levels of CK-MB and LDH were not significantly different from those in the LPS group (P>0.05).

[0107] 3. Test results of liver and kidney function indicators of each group of animals.

[0108] Fig. 9 This is a graph showing the blood biochemical test results of LPS-induced septic mice after treatment with sodium caprylate provided in this example.

[0109] Fig. 9 Middle (A) is the ALT test result diagram; Fig. 9 Middle (B) is the AST test result diagram; Fig. 9 Middle (C) is the Albumin test result diagram; Fig. 9 Middle (D) is the SCr test result diagram; Fig. 9 Middle (E) is the BUN test result diagram; Fig. 9 Middle (F) is the lactate test result diagram; Fig. 9 n = 7. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

[0110] Depend on Fig. 9 It can be seen that compared with the mice in the Control group, the levels of alanine aminotransferase ALT, aspartate aminotransferase AST, urea nitrogen BUN and lactic acid in the septic mice in the LPS group were significantly increased, and the albumin level was significantly decreased, indicating that the septic mice had liver and kidney dysfunction, multiple organ damage, and insufficient tissue perfusion. Compared with the mice in the LPS group, the ALT and lactic acid levels of the mice in the LPS+SO group were significantly decreased, but the AST, BUN and albumin levels did not change significantly.

[0111] (IV) Mouse heart pathological staining and reactive oxygen species staining:

[0112] 12 hours after LPS injection, the left ventricle of mice was quickly obtained, fixed, embedded, and sliced, and then HE staining, DHE staining and other methods were used to detect cardiac pathological damage and oxidative stress levels.

[0113] The specific test results are as follows:

[0114] Fig.10 The pathological changes of heart tissue in LPS-induced sepsis mice after sodium octanoate treatment were evaluated by HE staining for this example. Scale bar = 100 μm.

[0115] Depend on Fig.10 The results of cardiac pathological damage detection in each group of animals showed that the myocardial stripes of the mice in the Control group were clear and the myocardial cells were neatly arranged. However, the myocardial fibers of the mice in the LPS group were disordered, the myocardial cells were arranged in a disordered manner, the myocardial interstitium was edematous and congested, and the inflammatory cell infiltration was obvious. The above pathological changes in the cardiac tissues of the mice in the LPS+SO Q4h group were alleviated.

[0116] Fig.11 Representative images of DHE staining of mouse heart cryosections after LPS injection and sodium octanoate treatment are provided for this example. Fig.11 In the middle, red represents DHE-positive areas, and blue represents DAPI-positive areas. n = 3 per group. Scale bar = 100 µm.

[0117] because Fig.11 The results of DHE staining for cardiac oxidative stress in animals of each group showed that compared with those of the Control group, the DHE fluorescence intensity and positive area of ​​the hearts of the mice in the LPS group were significantly increased, while the DHE fluorescence intensity and positive area of ​​the hearts of the mice in the LPS+SO group were decreased compared with those of the LPS group, indicating that sodium octanoate can reduce the elevated ROS level in the hearts of mice induced by LPS.

[0118] Example 3 Survival analysis and detection

[0119] Thirty 8-week-old male C57BL / 6 mice weighing 20-25 g were randomly divided into three groups: Control group, LPS group and LPS+SO group, with n=10 in each group.

[0120] Mice in the LPS group were intraperitoneally injected with 20 mg / kg LPS to establish sepsis models;

[0121] The control group was intraperitoneally injected with an equal volume of PBS;

[0122] In the LPS+SO group, sodium octanoate was administered to mice within 30 minutes after intraperitoneal injection of LPS at a dose of 160 mg / kg, and then the administration was repeated every 4 hours. At the same time as sodium octanoate was administered, the mice in the LPS group were given an equal amount of normal saline. LPS+SO was administered three times in total, and then the administration was stopped. The mice in each group were then observed for 6 days, and the time of death of the mice was recorded. The survival rate of the mice in each group was described by the Kaplan-Meier curve, and the statistical differences between the groups were analyzed using the Log-rank test.

[0123] Fig.12 This is a graph showing the effect of sodium caprylate on the survival rate of septic mice provided in this example. Fig.12After LPS injection and sodium octanoate treatment, the mice were observed for 6 days, the death time of mice in each group was recorded, and the survival curve was drawn. n=10. * P<0.05, ** P<0.01, *** P<0.001, **** P<0.0001.

[0124] Depend on Fig.12 The results of the survival prognosis analysis of animals in each group showed that all mice in the LPS group died within 36 hours after LPS injection, while the death time of mice in the LPS+SO Q4h group was significantly delayed, and some mice were still alive after 6 days, indicating that the application of sodium octanoate in the early stage of sepsis can significantly reduce the mortality rate of septic mice.

[0125] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. Application of sodium caprylate in the preparation of drugs for treating sepsis.

2. The use according to claim 1, characterized in that: The applications include: (A) Inhibit sepsis-induced inflammatory storm; (B) Alleviate sepsis-induced multiple organ dysfunction; (C) Prolong survival in sepsis.

3. The use according to claim 2, characterized in that: The sepsis-induced inflammatory storm includes: In the state of sepsis, the inflammatory factors TNF-α, IL-1β and IL-6 are highly expressed in plasma.

4. The use according to claim 2, characterized in that: The sepsis-induced multiple organ dysfunction includes: Heart dysfunction, liver dysfunction, and kidney dysfunction.

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