Use of sodium phorbol in the preparation of products for promoting liver regeneration and reducing blood ammonia

Abstract

The application relates to the field of biological medicine, in particular to application of sodium tiglate in preparation of products for promoting liver regeneration and reducing blood ammonia; it is found and disclosed for the first time in the application that sodium tiglate can be applied to preparation of liver regeneration or liver function recovery products, liver cell proliferation capacity of residual liver after partial hepatectomy can be improved by using sodium tiglate, blood ammonia level after liver surgery is controlled, nitrogen metabolism disorder is improved by promoting conversion of blood ammonia into urea, and liver cell regeneration capacity is improved; the application of sodium tiglate provides a new treatment strategy with clear action mechanism and wide development prospect for treatment of insufficient liver regeneration after partial hepatectomy and hyperammonemia.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to the application of sodium crotonate in the preparation of products that promote liver regeneration and reduce blood ammonia. Background Technology

[0002] The liver possesses a remarkable regenerative capacity, maintaining essential physiological functions during acute or chronic injury. This significant characteristic makes liver transplantation or partial hepatectomy an effective strategy for treating end-stage liver disease. However, injury-induced disturbances of the liver microenvironment can significantly impair hepatocyte regeneration, contributing to liver disease remaining a leading cause of death worldwide.

[0003] Sodium crotonate is a short-chain fatty acid analog with wide applications. Due to its good water solubility and bioavailability, it has attracted considerable attention in recent years for its role in the treatment of intestinal diseases. The mechanisms by which sodium crotonate exerts its biological effects are complex and diverse, and its multi-target potential requires further investigation. Sodium crotonate can act not only as a histone modification regulator, increasing histone crotonylation levels and influencing the regulation of a series of genes related to cell cycle, proliferation, and anti-inflammation, but also as an energy substrate, providing energy support for cell proliferation. This may potentially affect hepatocyte metabolic reprogramming, enhance fatty acid oxidation and mitochondrial function, and provide energy support for cell proliferation. However, there is currently no direct evidence that sodium crotonate can systematically promote liver regeneration.

[0004] Hyperammonia, a common metabolic complication in patients with liver failure and cirrhosis, is not only an important marker of liver decompensation but also an independent risk factor for inhibiting liver regeneration. Studies have shown that ammonia can directly inhibit hepatocyte proliferation by inducing mitochondrial dysfunction, oxidative stress, and autophagic flux blockade. Simultaneously, hyperammonia can activate hepatic stellate cells, promote the formation of a fibrotic microenvironment, and interfere with the immune repair function of macrophages, further exacerbating regenerative impairment.

[0005] Compared to other regenerative drugs, sodium crotonate has multiple regulatory mechanisms and, as an endogenous metabolite derivative, has a relatively high safety profile. Therefore, in-depth research on the role of sodium crotonate in liver regeneration and its regulatory mechanism on blood ammonia will not only help enrich the theoretical basis of liver regeneration, but may also provide new intervention strategies for regenerative diseases such as liver failure and post-hepatectomy. Summary of the Invention

[0006] The purpose of this invention is to provide the application of sodium crotonate in the preparation of products that promote liver regeneration and reduce blood ammonia levels; aiming to improve the poor prognosis and risk of liver failure caused by insufficient liver regeneration capacity or elevated blood ammonia levels after partial hepatectomy or living donor liver transplantation, which has important clinical significance for improving liver tissue regeneration capacity and promoting postoperative liver function recovery.

[0007] The technical solution adopted to achieve the purpose of this invention is: Sodium crotonate is commonly used in food preservation, feed additives, and organic synthesis intermediates, but its application in liver regeneration and blood ammonia regulation has not been reported in the literature. However, this study unexpectedly discovered during the experiment that sodium crotonate can significantly promote the recovery of liver biochemical indicators to normal physiological ranges, demonstrating a good liver function repair effect. More importantly, the experiment further confirmed that sodium crotonate can effectively reduce serum ammonia levels after partial hepatectomy and alleviate the neurotoxic damage caused by hyperammonemia.

[0008] This application relates to the use of sodium crotonate in the preparation of products that promote liver regeneration or liver function recovery.

[0009] Furthermore, the application involves using sodium crotonate to lower blood ammonia levels or reduce ammonia toxicity to promote liver regeneration or liver function recovery. Lowering blood ammonia levels not only helps alleviate the neurotoxic damage caused by hyperammonemia and reduces the probability of insufficient liver regeneration combined with hyperammonemia, but also promotes liver cell proliferation.

[0010] Furthermore, the application involves using sodium crotonate to promote hepatocyte proliferation, thereby promoting liver regeneration or restoring liver function.

[0011] Furthermore, the application involves using sodium crotonate to upregulate the expression of hepatocyte proliferation-related proteins to promote hepatocyte proliferation.

[0012] Furthermore, the application involves using sodium crotonate to upregulate the expression of hepatocyte proliferation-related proteins to promote hepatocyte proliferation.

[0013] Furthermore, the protein is PCNA.

[0014] Furthermore, the liver in question is a liver that has undergone partial hepatectomy or liver transplantation.

[0015] Furthermore, the portion of the liver removed does not exceed 70% of the original liver volume.

[0016] Furthermore, the product that promotes liver regeneration or liver function recovery can promote liver regeneration after liver resection or liver transplantation.

[0017] Furthermore, the aforementioned product promoting liver regeneration or liver function recovery can improve the liver's ability to recover after liver resection or liver transplantation.

[0018] Based on the above research findings, this application further discloses the use of sodium crotonate in the preparation of products that promote hepatocyte proliferation.

[0019] The application of sodium crotonate in the preparation of blood ammonia-lowering products is further disclosed.

[0020] This application also relates to a pharmaceutical composition containing sodium crotonate for promoting liver regeneration or liver function recovery, said pharmaceutical composition comprising sodium crotonate and a pharmaceutically acceptable carrier thereof, formulated into a pharmaceutically acceptable dosage form.

[0021] It also relates to a pharmaceutical composition containing sodium crotonate that promotes hepatocyte proliferation, said pharmaceutical composition comprising sodium crotonate and a pharmaceutically acceptable carrier thereof, formulated into a pharmaceutically acceptable dosage form.

[0022] It also relates to a pharmaceutical composition for lowering blood ammonia containing sodium crotonate, said pharmaceutical composition comprising sodium crotonate and a pharmaceutically acceptable carrier thereof, formulated into a pharmaceutically acceptable dosage form.

[0023] Furthermore, the pharmaceutically acceptable carrier in the above-mentioned pharmaceutical composition is at least one of a solvent, buffer, isotonic agent, filler, lubricant, binder, disintegrant, and flow aid.

[0024] Furthermore, the dosage form of the above-mentioned pharmaceutical composition is a tablet, capsule, or injection.

[0025] Furthermore, the dosage of sodium crotonate in the above-mentioned pharmaceutical composition is at least 80 mg / kg / day.

[0026] Compared with the prior art, the beneficial effects of the present invention are: During the research process of this application, it was discovered for the first time that sodium crotonate can promote the proliferation of hepatocytes in the residual liver after partial hepatectomy and reduce blood ammonia levels, which has important clinical application value, especially in the preparation of products that promote liver regeneration, restore liver function and reduce blood ammonia levels, providing important experimental evidence for the development of new hepatoprotective drugs.

[0027] Forty-eight hours after administration, the liver-to-body weight ratio in the treatment group was significantly higher than that in the control group, upregulated by 1.3 times. This indicates that the regenerative capacity of the remaining liver in mice was enhanced and liver weight recovered rapidly after sodium crotonate injection. Serological tests showed that serum AST levels in mice were downregulated by 1.3 times after administration, while ALT levels were not significantly different from those in the control group, indicating that the degree of liver damage in mice was reduced after sodium crotonate treatment. Further immunofluorescence and Western blot analysis confirmed that the number of Ki67-positive cells in the liver tissue of mice in the treatment group was significantly upregulated by 2.2 times and the expression level of PCNA protein was upregulated by 1.6 times compared with the control group. These results consistently indicate that sodium crotonate significantly increased the number of proliferating cells in the liver and effectively promoted postoperative liver regeneration.

[0028] Results of blood ammonia and blood urea nitrogen (BUN) levels showed that sodium crotonate plays an important role in reducing blood ammonia levels and promoting ammonia metabolism: blood ammonia levels in the treatment group were significantly lower than those in the control group, downregulated by 1.6 times, while blood urea nitrogen levels were upregulated by 1.2 times. Sodium crotonate can promote the conversion of blood ammonia to urea and effectively reduce the concentration of ammonia in the blood by enhancing the ammonia detoxification pathway, thereby improving the metabolic disorder caused by elevated blood ammonia levels and providing a new intervention strategy for regulating blood ammonia levels. Attached Figure Description

[0029] Figure 1 This invention illustrates the effect of partial hepatectomy on the liver-to-body ratio in three groups of mice after the procedure. Figure a shows the experimental design and administration regimen of the animal experiment, while Figure b shows the liver-to-body ratio (n=6) of the three groups of mice after partial hepatectomy.

[0030] Figure 2 This invention describes the detection of serum biochemical indicators in three groups of mice after partial hepatectomy; where a represents the detection of AST content (n=6) in the serum of the three groups of mice, and b represents the detection of ALT content (n=6) in the serum of the three groups of mice.

[0031] Figure 3 This invention describes the detection of liver regeneration capacity in three groups of mice after partial hepatectomy; where a represents the results of HE and Ki67 immunofluorescence staining of the livers of the three groups of mice and the quantitative results of Ki67 positive cell rate (n=6); b represents the expression level and gray value quantitative results of the PCNA protein, a proliferation marker in the livers of the three groups of mice (n=6).

[0032] Figure 4 The effects of partial hepatectomy on serum ammonia and blood urea nitrogen levels in three groups of mice in this invention are shown in Figure 1. Figure 2 shows the serum ammonia levels (n=6) in the three groups of mice, and Figure 3 shows the serum urea nitrogen levels (n=6) in the three groups of mice. Detailed Implementation

[0033] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0034] It should be noted that, unless otherwise specified, the embodiments and features described in the present invention can be combined with each other.

[0035] Example 1: Preparation of sodium crotonate solution The crotonic acid crystals used in this application were purchased from Macklin, catalog number C804528.

[0036] Accurately weigh 8.6g of crotonic acid crystals and place them in a suitable container. Add 4mL of DMSO solution to the container and use an automated ultrasonic homogenizer to fully dissolve the crotonic acid crystals. The pH value of the solution should be approximately 2.0-3.0.

[0037] Weigh out 40g of solid NaOH and dissolve it in 1L of ultrapure water to prepare a 1M NaOH solution. Slowly add the 1M NaOH solution dropwise to the crotonic acid solution while stirring, and adjust the pH to 7.0. Add ultrapure water to bring the volume of the solution to 40mL, thus obtaining a 2.5mol / L sodium crotonate (NaCr) solution.

[0038] Example 2: Partial Hepatectomy in Mice Experimental animals were purchased from Jiangsu Jicui Yaokang Biotechnology Co., Ltd. Healthy 6-8 week old C57BL / 6J mice, weighing 22-23g, were selected and fasted for 12 hours preoperatively (with free access to water). General anesthesia was administered using inhaled isoflurane. The surgical area was prepared and disinfected. A midline incision was made in the upper abdomen to access the laparotomy. The liver lobes were freed, and the left lateral lobe, middle lobe, and caudate lobe were identified. The pedicles of the left lateral and middle lobes were ligated with 5-0 silk sutures to avoid damage to surrounding tissues. The liver lobes, totaling approximately 70% of the liver weight, were completely removed distal to the ligation lines. After confirming the absence of active bleeding, the abdominal wall and skin were sutured layer by layer with 6-0 absorbable sutures. Mice were housed on warming mats until awakening, and after resuming feeding, they were provided with high-sugar water for energy supplementation.

[0039] Example 3 Animal Experiment Protocol C57BL / 6J mice were randomly divided into three groups: sham operation group (Sham), control group (PBS), and drug administration group (NaCr), with 7 mice in each group.

[0040] On days 1-3 of the experiment, the sham-operated group and the control group were intraperitoneally injected with PBS, while the treatment group was intraperitoneally injected with NaCr solution (80 mg / kg / d), diluted 30 times with 2.5 mol / L sodium crotonate solution, with an injection volume of approximately 200 μL. Each mouse received approximately 1.84 mg of sodium crotonate daily, administered once daily. On day 4, both the control and treatment groups underwent partial hepatectomy, while the sham-operated group only required laparotomy followed by suturing. Postoperatively, intraperitoneal injections of PBS or NaCr solution continued, and tissue samples were harvested 48 hours after the partial hepatectomy. To obtain the liver, mice were first subjected to terminal blood collection via enucleation, and then immediately euthanized using cervical dislocation. Subsequently, laparotomy was performed immediately to completely remove the liver. After removing any visible necrotic parts, the liver tissue was rinsed with pre-cooled sterile saline to remove residual blood. Finally, the surface moisture was blotted dry with sterile filter paper, and the tissue was accurately weighed and the data recorded. The livers of mice from the same lobe were divided into two portions. One portion was fixed in 4% paraformaldehyde solution for HE and Ki67 staining; the other portion was flash-frozen in liquid nitrogen and stored at -80°C for Western blotting.

[0041] Example 4: Detection of Serum Biochemical Indicators Whole blood samples were allowed to stand at room temperature for 1-2 hours to allow for complete coagulation. They were then centrifuged at 3000 rpm for 15 minutes at 4°C. The supernatant was collected as serum, aliquoted, and stored at -80°C for later testing, avoiding repeated freeze-thaw cycles. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were determined using a rate method. The principle is as follows: ALT catalyzes the reaction of alanine with α-ketoglutarate to produce pyruvate and glutamate; AST catalyzes the reaction of aspartate with α-ketoglutarate to produce oxaloacetate and glutamate. Subsequently, the generated pyruvate or oxaloacetate, in the presence of coenzyme NADH, is further catalyzed by lactate dehydrogenase (LDH) or malate dehydrogenase (MDH), leading to the oxidation of NADH to NAD+, resulting in a decrease in absorbance at 340 nm. This rate is directly proportional to the activity of ALT or AST in the serum. The specific procedures were strictly performed in accordance with the instructions for the commercially available kits. Both the ALT and AST kits were purchased from Elabscience, catalog numbers E-BC-K235-S and E-BC-K236-M, respectively. Thawed serum samples were mixed with the reaction substrate reagents in the specified proportions, and the absorbance at 340 nm was immediately monitored over time using an automated biochemical analyzer. The enzyme activity units (U / L) per liter of serum were calculated and reported using a standard curve. Quality control samples were included in all assays to ensure accuracy.

[0042] Example 5: HE staining of liver tissue Liver tissue was fixed in 4% paraformaldehyde solution for 48 hours, then dehydrated with graded ethanol, cleared with xylene, and embedded in paraffin to form paraffin blocks. The tissue blocks were serially sectioned using a rotary microtome to a thickness of 5 μm, spread in 45°C warm water, attached to glass slides, and dried overnight in a 60°C oven to ensure tight adhesion of the tissue.

[0043] The staining procedure is as follows: Immerse the sections sequentially in xylene I and II for 10 minutes each to completely dewax them, then pass them through a gradient of 100%, 95%, 85%, and 70% ethanol for 5 minutes each, finally settling in water. Rinse with distilled water. Immerse the sections in Harris hematoxylin stain for 5-8 minutes, then rinse with running tap water for 10 minutes to regain blue color. Differentiate with 1% hydrochloric acid ethanol solution for a few seconds, then immediately rinse again with running tap water to regain blue color, observing under a microscope until the contrast between the cell nucleus and cytoplasm is clear. Counterstain the sections in 0.5% eosin Y aqueous solution for 1-3 minutes. Rapidly dehydrate with 95% ethanol I and II and 100% ethanol I and II for approximately 30 seconds each. Then clear the sections by immersing them in xylene I and II for 5 minutes each. Remove the sections from the xylene, aspirate excess liquid, add neutral resin, and cover with a coverslip for mounting. Store the mounted sections at room temperature away from light. After the resin has solidified, observe and acquire images under an optical microscope.

[0044] Example 6: Ki67 staining of liver tissue Liver paraffin sections were dewaxed, hydrated, and antigen-retrieved. They were then permeabilized with PBS containing 0.3% Triton X-100 and blocked with 5% BSA at room temperature for 1 hour. The sections were then incubated overnight at 4°C with rabbit anti-Ki67 primary antibody. After thorough washing with PBS, they were incubated with fluorescently labeled anti-rabbit IgG secondary antibody at room temperature in the dark for 1 hour. After washing with PBS, the cell nuclei were counterstained with DAPI for 10 minutes. After a second wash, the sections were mounted with anti-fluorescence quenching mounting medium. Finally, the sections were observed and images acquired under a fluorescence microscope.

[0045] Example 7: Western blot of liver tissue Liver tissue was washed with pre-cooled PBS and homogenized thoroughly on ice in RIPA lysis buffer (containing protease and phosphatase inhibitors). The lysis buffer was centrifuged at 12000×g for 15 minutes at 4°C, and the supernatant was collected as total protein. Protein quantification was performed using the BCA method, followed by mixing with 5× loading buffer and boiling at 100°C for 10 minutes to denature the proteins. Equal volumes of protein were separated by SDS-PAGE electrophoresis and wet-transferred to a PVDF membrane. The membrane was blocked with 5% skim milk at room temperature for 1 hour, then incubated overnight at 4°C with PCNA or Tubulin primary antibody. After washing with PBST, the membrane was incubated with HRP-labeled secondary antibody at room temperature for 1 hour, developed with ECL chemiluminescence reagent, and the signal was acquired and analyzed using a gel imaging system.

[0046] Example 8: Blood Ammonia Detection Solarbio's Serum Ammonia Assay Kit (catalog number BC4385, specification 100T / 96S) is based on the indophenol blue colorimetric principle for the quantitative determination of ammonia levels in serum / plasma, with a detection wavelength of 630 nm. The kit consists of 25 mL of extraction buffer, 2.5 mL of Reagent I (Solution A), 10 mL of Reagent I (Solution B), 12 mL of Reagent II, and one vial of 100 μmol / mL ammonia standard. All components should be stored at 2-8℃. Before use, Reagent I should be prepared at a ratio of A:B = 1:4, and the standard should be diluted with distilled water to a concentration of 2 μmol / mL. Take 40 μL of serum / plasma (test tube), 40 μL of diluted standard (standard tube), and 40 μL of distilled water (blank tube) and add them to EP tubes respectively. Add 200 μL of extraction buffer to each tube, mix thoroughly, centrifuge at 8000 rpm for 10 min, take 100 μL of supernatant, and add 100 μL of reagent one and 100 μL of reagent two in sequence. Mix well and incubate at 37℃ for 20 min. After the reaction is complete, take 200 μL of the reaction solution and measure the absorbance at 630 nm. Calculate ΔAdetermined = Atest tube - Ablank tube, ΔAstandard = Astandard tube - Ablank tube. The formula for calculating blood ammonia content is: Blood ammonia (μmol / mL) = 2 × ΔAdetermined ÷ ΔAstandard.

[0047] Example 9 Blood Urea Nitrogen Detection Solarbio Urea Nitrogen (Urea) Content Assay Kit (Catalog No. BC1535, Specification 100T / 48S) uses the indophenol blue colorimetric method to quantitatively determine the urea nitrogen content in serum / plasma, with a detection wavelength of 630nm. The kit consists of Reagent 1 (powder × 2 vials), Reagent 2 (15mL), Reagent 3A solution (3mL), Reagent 3B solution (12mL), Reagent 4 (10mL), and standard (powder), all stored at 2-8℃. Prepare Reagent 1 immediately before use: dissolve thoroughly in 5mL distilled water per vial; Prepare Reagent 3 immediately at a ratio of A solution:B solution = 0.1:0.4; Prepare the standard solution by adding 4.66mL distilled water to a 1mg / mL urea nitrogen standard solution, and dilute 25μL of the standard solution with 975μL distilled water to a working solution of 25μg / mL before use. Serum samples can be directly tested without pretreatment. Take 20 μL of serum (test tube), 20 μL of standard working solution (standard tube), and 20 μL of distilled water (blank tube) and add them to EP tubes respectively. Add 40 μL of reagent one to each tube, mix well, and react at 37℃ for 10 min. Then add 70 μL of reagent two and 70 μL of reagent three in sequence, mix well, and develop color at 37℃ for 10 min. Measure the absorbance at 630 nm. The formula for calculating blood urea nitrogen content is: Blood urea nitrogen (mg / L) = 5 × (A test - A blank) ÷ (A standard - A blank).

[0048] Example 10 Data Analysis All data are expressed as mean ± standard deviation (mean ± SD). Statistical analysis was performed using GraphPad Prism 9.0 software, and protein band grayscale detection was processed using ImageJ software. Independent samples t-tests were used for comparisons between two groups, with p < 0.05 considered statistically significant. All experiments were repeated at least three times to ensure the stability and reproducibility of the results.

[0049] The experimental results are as follows: (1) Mouse liver-to-body weight ratio like Figure 1 The figure shows the effect of partial hepatectomy on the liver-to-body weight ratio in mice. Figure a is a schematic diagram of the animal experimental design and drug administration regimen. Forty-eight hours after partial hepatectomy, liver samples were taken from the sham-operated group (Sham), the control group (PBS), and the drug-treated group (NaCr) for analysis. The liver-to-body weight ratio results, as shown in Figure b, are as follows: the liver-to-body weight ratio in the drug-treated group (NaCr) was significantly higher than that in the control group (PBS), upregulated by 1.3 times. This indicates that the regenerative capacity of the remaining liver in mice treated with NaCr was stronger than that in the control group.

[0050] (2) Serum biochemical indicators Serum biochemical index test results as follows Figure 2 As shown in the figure, a represents the AST content (n=6) in the serum of the three groups of mice, and b represents the ALT content (n=6) in the serum of the three groups of mice. The serum AST and ALT results showed that the serum AST in the NaCr-treated group (NaCr) was significantly lower than that in the control group (PBS), downregulated by 1.3 times, while ALT showed no significant difference. This indicates that the degree of liver damage in mice treated with NaCr was reduced compared to the control group (PBS).

[0051] (3) HE and Ki67 staining, WB staining of liver tissue The liver regeneration capacity of three groups of mice after partial hepatectomy was tested, and the results are as follows: Figure 3 As shown in Figure 1, a) presents the results of HE and Ki67 immunofluorescence staining of liver tissues in three groups of mice and the quantitative results of Ki67-positive cell rate (n=6). HE staining of the liver showed that the liver tissues of mice in each group were normal, with no necrotic areas. Ki67 fluorescence staining results indicated that the number of Ki67-positive cells in the liver tissue of mice in the treatment group (NaCr) was significantly higher than that in the control group (PBS), upregulated by 2.2-fold. b) shows the Western blotting results of the expression level and grayscale value of the liver proliferation marker PCNA protein in mice after sodium crotonate administration (n=6). The results also showed that the expression level of the liver cell proliferation marker PCNA protein in the treatment group (NaCr) was significantly stronger than that in the control group (PBS), upregulated by 1.6-fold. These results indicate that sodium crotonate treatment can upregulate the expression of the hepatocyte proliferation-related protein PCNA, thereby promoting cell proliferation in the liver of mice after partial hepatectomy and promoting liver regeneration.

[0052] (4) Blood ammonia and blood urea nitrogen levels The blood ammonia and blood urea nitrogen levels in mice after partial hepatectomy were tested, and the results are as follows: Figure 4 As shown in Figure 1, serum ammonia levels in mice after sodium crotonate administration are displayed in Figure 2, and serum urea nitrogen levels are displayed in Figure 3. Combining the results of sodium crotonate administration in Figures 1 and 2, the serum ammonia levels in the treatment group were significantly lower than those in the control group (down-regulation by 1.6-fold), while serum urea nitrogen levels were higher (up-regulation by 1.2-fold). This indicates that NaCr treatment converts serum ammonia into urea, thereby reducing serum ammonia levels.

[0053] Based on the above experimental conclusions, it can be found that sodium crotonate can convert blood ammonia into urea. It may effectively reduce the concentration of ammonia in the blood by enhancing the expression of key enzymes in the urea cycle of hepatocytes and mitochondrial function, thereby reducing the inhibitory effect of high blood ammonia on liver regeneration after partial hepatectomy. In turn, it can promote the proliferation of hepatocytes in the residual liver tissue after partial hepatectomy, effectively accelerate the process of liver regeneration and liver recovery, and reduce the risk of poor prognosis, insufficient liver regeneration combined with hyperammonemia and liver failure.

[0054] The above description is only a preferred embodiment of the present invention. It should be noted that, for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. Application of sodium crotonate in the preparation of products that promote liver regeneration or liver function recovery.

2. The application of sodium crotonate as described in claim 1 in the preparation of products that promote liver regeneration or liver function recovery, characterized in that: The application involves using sodium crotonate to lower blood ammonia levels or reduce ammonia toxicity, thereby promoting liver regeneration or restoring liver function.

3. The application of sodium crotonate as described in claim 1 in the preparation of products that promote liver regeneration or liver function recovery, characterized in that: The application involves using sodium crotonate to promote hepatocyte proliferation, thereby promoting liver regeneration or restoring liver function.

4. The application of sodium crotonate as described in claim 3 in the preparation of products that promote liver regeneration or liver function recovery, characterized in that: The application involves using sodium crotonate to upregulate the expression of hepatocyte proliferation-related proteins to promote hepatocyte proliferation.

5. The use of sodium crotonate as described in any one of claims 1-4 in the preparation of products that promote liver regeneration or liver function recovery, characterized in that: The product that promotes liver regeneration or liver function recovery can promote liver regeneration after liver resection or liver transplantation.

6. The use of sodium crotonate as described in any one of claims 1-4 in the preparation of products that promote liver regeneration or liver function recovery, characterized in that: The aforementioned products that promote liver regeneration or liver function recovery can improve the liver's ability to recover after liver resection or liver transplantation.

7. Application of sodium crotonate in the preparation of products that promote hepatocyte proliferation.

8. Application of sodium crotonate in the preparation of blood ammonia-lowering products.

9. A pharmaceutical composition containing sodium crotonate for promoting liver regeneration or liver function recovery, characterized in that: The pharmaceutical composition comprises sodium crotonate and its pharmaceutically acceptable carrier.

10. The pharmaceutical composition containing sodium crotonate for promoting liver regeneration or liver function recovery as described in claim 9, characterized in that: The pharmaceutically acceptable carrier is at least one of the following: solvent, buffer, isotonic agent, filler, lubricant, binder, disintegrant, and glidant.

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