Application of oxytocin in preparation of medicine for preventing or treating postoperative cognitive impairment and medicine

Abstract

The invention discloses application of oxytocin to preparation of a medicine for preventing and treating postoperative cognitive impairment and the medicine. The invention discloses a mechanism of the oxytocin for preventing or treating the postoperative cognitive impairment for the first time, finds that the oxytocin can promote the expression of PI3K / Akt / mTOR pathway related protein in the hippocampal brain region and relieve the activation of microglial cells in the hippocampal brain region for the first time, and can prevent or treat the postoperative cognitive impairment by being locally administrated to the hippocampal brain region. The invention provides the application of oxytocin in the medicine for preventing or treating the postoperative cognitive impairment, and provides a new thought for the medicine for preventing or treating the postoperative cognitive impairment.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to drugs for the prevention or treatment of postoperative cognitive impairment with oxytocin as the active ingredient. Background Technology

[0002] With the increasing severity of health problems worldwide, the number of surgical procedures has risen dramatically, becoming one of the main means of treating diseases. According to global surgical statistics published by the World Health Organization (WHO), the number of surgeries performed globally reaches 320 million annually and is still gradually increasing. Postoperative neurocognitive disorders (PND) are a common perioperative complication of the central nervous system. Studies report that the incidence of PND on day 7 post-surgery is between 41% and 75%, and the incidence at 3 months post-surgery is between 18% and 45%. Advanced age is an independent risk factor for postoperative cognitive disorders. Elderly patients have lower resistance to stress and relatively lower tolerance for surgery, leading to a higher incidence of PND. Studies have shown that in people over 65 years of age, the rate of PND occurring one week post-surgery is close to 54%. Currently, the pathogenesis of PND is unclear, but it is likely the result of multiple factors working together. Neuroinflammation, changes in synaptic properties, and abnormal accumulation of β-amyloid protein (Aβ) may all be involved in the pathological development of PND. It is important to note that postoperative cognitive impairment (PND) not only leads to prolonged hospital stays, increased costs, and higher readmission rates, but may also increase the 5-year mortality rate after surgery. PND not only reduces the individual's quality of life but can also place a heavy burden on families and society. Although the pathological mechanisms of postoperative cognitive impairment have been gradually explored and discovered, effective prevention and treatment methods are still lacking in clinical practice. Exploring the specific etiological mechanisms of PND in elderly patients and finding new interventions is of great significance.

[0003] Oxytocin has great potential in alleviating cognitive-related neurological disorders.

[0004] Oxytocin (OXT) is a nonapeptide hormone synthesized by the hypothalamus and released by the neurohypophysis, playing a wide range of roles in reproductive physiology, social behavior, and mental health. Oxytocin stimulates uterine muscle contractions and promotes the production of prostaglandins, which in turn enhance uterine contractions. Therefore, it is clinically used in the childbirth process. However, oxytocin also has potential research value in regulating social dynamics, metabolism, and pain relief. Oxytocin is known as a "social hormone" due to its role in promoting prosocial behavior. However, recent studies have shown that its effects are significantly situation-dependent and bidirectional: oxytocin can enhance social reward behavior by activating dopaminergic neurons in the nucleus accumbens, significantly improving trust and emotional recognition accuracy (especially the recognition of fear expressions) in healthy individuals. Animal models have confirmed that oxytocin can increase mother-infant contact time (mouse model) and mate preference (prairie vole experiment), with the mechanism involving the regulation of the prefrontal cortex-amygdala neural circuit. Clinically, abnormally enhanced social avoidance behavior has been observed in some patients with autism spectrum disorder, which may be related to signal transduction dysregulation caused by abnormal oxytocin receptor expression. Oxytocin reduces relapse behavior by 40% in a cocaine addiction model by inhibiting dopamine neuron activity in the ventral tegmental area, thus alleviating addictive behavior. Studies have shown that oxytocin can maintain the integrity of the blood-brain barrier and reduce memory impairment caused by ischemic injury after stroke. Research also indicates that oxytocin exerts an analgesic effect by projecting to oxytocinergic neurons in the prelimbic prelimbic central fossa (pl-PFC) and enhancing pl-PFC neuronal activity.

[0005] However, to date, there have been no studies or reports on the role of oxytocin in alleviating postoperative cognitive impairment (PND), and current technology has not yet discovered the role and mechanism of oxytocin in regulating PND. Summary of the Invention

[0006] The main objective of this invention is to provide an application of oxytocin in the preparation of drugs for the prevention and treatment of postoperative cognitive impairment, and a drug thereof, with the aim of effectively preventing and treating postoperative cognitive impairment.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] In a first aspect, the present invention proposes the application of oxytocin in the preparation of drugs for the prevention and treatment of postoperative cognitive impairment.

[0009] Optionally, the drugs for preventing and treating postoperative cognitive impairment are administered locally to the hippocampus.

[0010] Optionally, the drugs for preventing and treating postoperative cognitive impairment can promote the expression of PI3K / Akt / mTOR pathway-related proteins in the hippocampus.

[0011] Optionally, the medication for preventing and treating postoperative cognitive impairment can alleviate microglial cell activation in the hippocampus.

[0012] In a second aspect, the present invention provides a medicament for the prevention and treatment of postoperative cognitive impairment, the medicament comprising oxytocin.

[0013] Optionally, the drug may further comprise pharmaceutically acceptable excipients, carriers, and / or diluents.

[0014] Optionally, the concentration of oxytocin in the drug is 25 mg / L.

[0015] Compared with the prior art, the beneficial effects of the present invention are:

[0016] This invention reveals for the first time the mechanism by which oxytocin prevents or treats postoperative cognitive impairment, and for the first time discovers that oxytocin can promote the expression of PI3K / Akt / mTOR pathway-related proteins in the hippocampus, alleviate microglial cell activation in the hippocampus, and prevent or treat postoperative cognitive impairment by local administration to the hippocampus. This invention provides the application of oxytocin in drugs for the prevention or treatment of postoperative cognitive impairment and offers new ideas for drugs for the prevention or treatment of postoperative cognitive impairment. Attached Figure Description

[0017] Figure 1 This is a schematic diagram illustrating the effect of local administration of OXT in the hippocampus on the behavior of aged PND mice in an embodiment of the present invention.

[0018] Figure 1 -A represents the motion trajectory diagrams of the control group, surgery group, and surgery + OXT drug administration group in the new object recognition experiment;

[0019] Figure 1 -B is a graph showing the percentage of new object exploration time in the control group, surgery group, and surgery + OXT drug administration group in the new object recognition experiment;

[0020] Figure 1 -C represents the activity trajectory diagrams of the control group, the surgical group, and the surgical + OXT administration group in the water maze experiment;

[0021] Figure 1 -D is a graph showing the target quadrant dwell time of the control group, surgery group, and surgery + OXT drug administration group in the water maze experiment;

[0022] Figure 2 This is a schematic diagram of oxytocin and oxytocin receptor expression in the hippocampus of aged PND mice in an embodiment of the present invention;

[0023] Figure 2 -A shows confocal fluorescence imaging of the CA1 region of the hippocampus in the control and surgical groups stained with RNAscope.

[0024] Figure 2 -B is the relative fluorescence intensity map of the hippocampus brain region in the control group and the surgical group detected by qPCR experiment;

[0025] Figure 2 -C is a graph showing the relative expression intensity of oxytocin receptor mRNA in the hippocampus of the control group and the surgical group as detected by qPCR experiment;

[0026] Figure 2 -D is a graph showing the relative expression intensity of oxytocin mRNA in the hippocampus of the control group and the surgical group as detected by qPCR experiment;

[0027] Figure 3 This is a schematic diagram illustrating the effect of local administration of OXT in the hippocampus on the activation of microglia in the hippocampus of aged PND mice in an embodiment of the present invention.

[0028] Figure 3 -A shows immunofluorescence imaging of microglia in the hippocampus of the control group, surgery group, and surgery + OXT administration group.

[0029] Figure 3 -B is the relative intensity of immunofluorescence of microglia in the hippocampus of the control group, surgery group, and surgery + OXT administration group;

[0030] Figure 3 -C is a statistical graph of activated microglia per unit area in the hippocampus of the control group, surgery group, and surgery + OXT administration group;

[0031] Figure 4 This is a schematic diagram illustrating the effect of local administration of OXT in the hippocampus on the expression of PI3K / Akt / mTOR pathway-related proteins in the hippocampus of aged PND mice.

[0032] Figure 4 -A represents the relative expression level of PI3K signaling pathway mRNA in the hippocampus of the control group, surgery group, and surgery + OXT administration group;

[0033] Figure 4 -B represents the relative expression level of Akt signaling pathway mRNA in the hippocampus of the control group, surgery group, and surgery + OXT administration group;

[0034] Figure 4 -C represents the relative expression level of mRNA in the hippocampus mTOR signaling pathway in the control group, surgery group, and surgery + OXT administration group;

[0035] Figure 4 -D represents the expression level of PI3K / Akt / mTOR pathway-related proteins in the hippocampus of the control group, surgery group, and surgery + OXT administration group;

[0036] Figure 4-E is a density map of Akt / mTOR pathway-related proteins in the hippocampus of the control group, surgery group, and surgery + OXT administration group;

[0037] Figure 5 Electron micrographs of mitochondrial morphology and quantity in hippocampal neurons of the control group, surgery group, and surgery + OXT administration group. Detailed Implementation

[0038] The following detailed description, in conjunction with the accompanying drawings, illustrates the application of the oxytocin of the present invention in the preparation of drugs for the prevention or treatment of cognitive impairment, and provides a further detailed description of the drugs themselves.

[0039] Specifically, as one aspect of the technical solution of the present invention, it relates to the application of oxytocin in the preparation of drugs for the prevention or treatment of postoperative cognitive impairment.

[0040] In some preferred embodiments, the drug for preventing or treating postoperative cognitive impairment is administered locally to the hippocampus.

[0041] In some preferred embodiments, the drugs for the prevention and treatment of postoperative cognitive impairment are able to promote the expression of proteins related to the PI3K / Akt / mTOR pathway in the hippocampus.

[0042] In some preferred embodiments, the drugs for the prevention and treatment of postoperative cognitive impairment are able to alleviate microglial cell activation in the hippocampus.

[0043] Another aspect of the present invention provides a medicament for the prevention and treatment of postoperative cognitive impairment, the medicament comprising oxytocin.

[0044] In some preferred embodiments, the oxytocin concentration is 25 mg / L.

[0045] In some preferred embodiments, the drug also comprises pharmaceutically acceptable excipients, carriers, and / or diluents.

[0046] The technical solution of the present invention will be further described in detail below with reference to several preferred embodiments and accompanying drawings. This embodiment is implemented on the premise of the technical solution of the invention, and provides detailed implementation methods and specific operation processes. However, the protection scope of the present invention is not limited to the following embodiments.

[0047] Unless otherwise specified, the experimental materials used in the examples below can be purchased from conventional biochemical reagent companies.

[0048] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0049] Example 1: An experiment on the effects of oxytocin on postoperative cognitive impairment (PND) behavior in aged rats.

[0050] I. Animal grouping and administration

[0051] Male 15-month-old aged C57 mice were randomly divided into three groups (n=8): control group (Sham group), surgery group (PND group), and surgery + OXT administration group (PND+OXT group). On the 3rd day after tibial fracture surgery, mice were stereotactically injected into the hippocampus for 5 consecutive days. Cognitive behavior was observed using the Morris water maze and novel object recognition experiments.

[0052] II. Surgical Procedure and Stereoscopic Drug Delivery in the Hippocampus

[0053] 2.1 Constructing a Postoperative Cognitive Disorder (PND) Model after Tibial Fracture Surgery

[0054] Surgical management of tibial fractures in the surgical group and the surgical + OXT administration group:

[0055] General anesthesia was administered using an anesthesia system with a constant oxygen flow rate of 0.2 L / min. Induction was performed in the induction chamber using 5% isoflurane, and the depth of anesthesia could be confirmed by pinching the toes. The medial aspect of the mouse's right hind limb was removed to expose the surgical area. A skin incision was made on the medial aspect of the right hind limb, extending downwards from the proximal knee joint to the midline of the right tibia. The midline of the tibia was exposed, and the diaphysis was visually located. The knee was bent, and a 0.5 mm hole was drilled in the intramedullary canal using a 25-gauge needle. A 0.38 mm stainless steel needle was inserted into the medullary canal approximately 15 mm through the hole until resistance was felt, and then a wire cutter was used to cut it flush with the tibial plateau.

[0056] Surgical treatment in the control group: only a skin incision was made to expose the midline of the tibia, without drilling or inserting steel pins.

[0057] 2.2 Stereoscopic localization of brain regions for drug delivery to the hippocampus

[0058] First, mice were anesthetized by intraperitoneal injection of 2% sodium pentobarbital (20 mg / kg), and then fixed in a stereotaxic apparatus. The animals' body temperature was maintained at 36°C using a heating pad. After fixation, the hair on the mice's heads was removed, and the scalp surface was disinfected with 75% alcohol to expose and level the skull. After leveling, the syringe needle was positioned above the target brain region for localization, and the cerebral cortex above the target brain region was exposed using a skull drill. The required drug was injected at a rate of 0.2 μL / min using a calibrated glass microelectrode (outer diameter 1.0 mm, inner diameter 0.58 mm, WPI, USA) connected to an infusion pump (micro4, WPI, USA). Coordinates were defined as dorsoventral (DV) from the brain surface, anterior-posterior (AP) from the brain, and mediaolateral (ML) from the midline (in mm).

[0059] III. Novel Object Recognition and Water Maze Experiment

[0060] 3.1 Morris Water Maze

[0061] This study used the classic behavioral method—the Morris Water Maze (MWM)—to assess the spatial cognitive function of mice. The experimental setup consisted of a circular stainless steel pool with a diameter of 110 cm and a height of 70 cm, a constant water depth of 35 cm, and a water temperature precisely controlled at 23 ± 1 °C to maintain normal metabolic levels in the mice. A four-quadrant design was employed, with highly recognizable visual markers placed on the outer walls to construct a spatial reference system. In specific quadrants, a 5 × 5 cm marker was concealed 0.8 cm below the water surface. 2 An acrylic escape platform was used. The animals' movements were fully recorded throughout the experiment using a top-mounted tracking system. After five days of systematic path learning, the underwater platform was removed on the sixth day of testing, while the entry position remained unchanged. Researchers focused on observing the mice's free exploration behavior for four minutes without the platform, analyzing their activity trajectory in the original platform area and the duration of stay in the target quadrant to quantitatively assess the consolidation of spatial memory.

[0062] 3.2 New Object Recognition Experiment

[0063] This study used the Novelty Recognition Test (NRT) system to assess the memory encoding ability of rodents. The experimental setup was 50×50×60cm. 3The polycarbonate behavioral observation chamber underwent standardized treatment to eliminate spatial reference cues. The experimental design consisted of two key phases: On the training day, animals were placed in the central area of ​​the chamber and pre-exposed to two identical objects (A1 / A2, 5cm from the chamber wall) placed symmetrically in space for 5 minutes of free exploration. An intelligent behavioral analysis system precisely recorded the cumulative time the animals' noses were in contact with the objects (defined as effective exploration time). After a 24-hour interval, the testing phase began, replacing one of the familiar objects with a new object (B) with significantly different morphological features, strictly replicating the initial spatial parameters. After the test, a gradient ethanol cleaning procedure was performed to completely eliminate any residual odor that might interfere with subsequent experiments. Data analysis used a relative exploration index: the percentage of time spent exploring the new object = (TB / (TA1+TB)) × 100%, which effectively reflects the animal's ability to recognize and remember new objects.

[0064] IV. Experimental Results

[0065] like Figure 1 As shown in -A and 1-B, compared with the control group (sham), aged mice in the tibial fracture surgery group (surgery) showed a significantly reduced time spent exploring new objects in the novel object recognition experiment, with a statistically significant difference (P < 0.05). Mice in the hippocampal OXT local administration group showed a significantly increased time spent exploring new objects compared with the surgery group. Similarly, as... Figure 1 As shown in -C and 1-D, local administration of OXT to the hippocampus alleviated the reduced time spent exploring target phenomena in mice during the water maze experiment caused by tibial fracture surgery.

[0066] The above results indicate that local administration of OXT to the hippocampus can alleviate post-tibial fracture surgery-induced pulmonary dysplasia (PND).

[0067] Example 2: Experiment on changes in oxytocin receptors and oxytocin in the hippocampus of aged PND rats

[0068] I. Animal grouping and administration are the same as in Example 1.

[0069] II. Molecular Experiments

[0070] 2.1 RNAscope staining to detect OXTR mRNA expression in the CA1 region of the hippocampus

[0071] Mice were anesthetized by intraperitoneal injection of 10% chloral hydrate (0.03-0.04 ml / 10 g); after anesthesia, the heart was perfused in vivo with 4% paraformaldehyde solution for fixation; the complete mouse brain was obtained and placed in a fixative solution at 4°C overnight for post-fixation treatment; it was dehydrated by a 10%, 20%, and 30% sucrose gradient, and then cryopreserved using OCT gel. After the samples were completely frozen, they were sectioned using a cryostat to a thickness of 30 μm. After air drying, the samples were pretreated with 50%, 70%, and 100% anhydrous ethanol and hydrogen peroxide. The samples were then incubated with Protease III in a 40°C water bath for 30 minutes, followed by incubation of the OXTR probe for 2 hours. After cleaning the samples, the signals were cascaded and amplified sequentially. The signal channels were blocked after staining with the matching fluorescent dye (570 nm, 1:1000). The samples were then washed with PBS for 10 min * 3 times and incubated at room temperature in the dark with Nissl reagent (435 / 455 nm, 1:400) for neuronal staining. After staining, the samples were mounted with an anti-fluorescence quencher and imaged using a fluorescence confocal microscope.

[0072] 2.2 qPCR assay to detect the expression of oxytocin receptor (OXTR) and oxytocin (OTX) mRNA in the hippocampus.

[0073] The quantitative PCR reaction system consisted of 20 μl of 2×SYBR Green Mastermix, containing 10 μl of each primer pair (5 μM) and 5 μl of cDNA template. All reactions were performed on a Roche LightCycler 480 system using LightCycler 480 SYBR Green I Mastermix premixed reagents. The cycling conditions were as follows: 95℃ pre-denaturation for 10 min; followed by 40 cycles of 95℃ denaturation for 10 s, 60℃ annealing for 10 s, and 72℃ extension for 20 s. Fluorescence signals were collected at the end of each 72℃ extension phase. Amplification specificity was verified by melting curve analysis. Three replicate wells were set for each sample, and the average cycle threshold (Ct) of each replicate well was calculated. The fold change in target gene expression was measured using β-actin as an internal reference gene, employing a 2×SYBR Green Mastermix. -ΔΔCt The method calculates relative mRNA expression levels. The primers used are as follows:

[0074] OXT:F-GCTGAAACTTGATGGCTCCG

[0075] R-TTCTGGGGTGGCTATGGG

[0076] OXTR:F-CTGAACATCCCGAGGAACTG

[0077] R-CTCTGAGCCACTGCAAATGA

[0078] III. Experimental Results

[0079] like Figure 2 As shown in AC, RNAscope staining and qPCR results both indicated no significant difference in oxytocin receptor mRNA expression in the hippocampus of aged mice in the tibial fracture surgery group compared to the sham surgery group. However, as... Figure 2 As shown in Figure D, compared with sham surgery, the expression of oxytocin in the hippocampus of aged mice in the tibial fracture surgery group was significantly downregulated, with a statistically significant difference (P < 0.05). These results suggest that the imbalance between OXT and OXTR expression in the hippocampus may be involved in regulating tibial fracture surgery-induced PND.

[0080] Example 3: Experiment on the activation of microglia in the hippocampus of aged PND mice by local administration of OXT to the hippocampus

[0081] I. Animal grouping and administration are the same as in Example 1.

[0082] II. Immunofluorescence Experiment

[0083] Mice were anesthetized by intraperitoneal injection of 50 mg / kg of 0.4% sodium pentobarbital. After anesthesia, the heart was perfused and fixed with 4% paraformaldehyde solution. Mouse brain tissue was harvested, fixed with 4% paraformaldehyde (PFA), removed, and further fixed in PFA. The tissue was then dehydrated in 30% sucrose and finally embedded in OCT to prepare 12–20 μm thick frozen sections. Sections were washed three times with PBS for 5 minutes each time, permeabilized with 0.3% Triton X-100 membrane for 10–15 minutes, and then blocked in 5–10% goat serum at room temperature for 1 hour. Rabbit anti-Iba-1 antibody (1:200, Abcam) was then diluted in serum-containing PBS and incubated overnight at 4°C. The next day, the sections were washed three times with PBS, and Alexa Fluor 594 secondary antibody (1:400, Invitrogen, A-11012) was added and incubated at room temperature in the dark for 1–2 hours. After washing with PBS again, the sections were mounted.

[0084] III. Experimental Results

[0085] like Figure 3 As shown in AC, compared with the sham surgery group, the expression of Iba-1, a marker of microglia activation in the hippocampus of aged mice was significantly increased in the tibial fracture surgery group (P < 0.05). In mice treated with local OXT in the hippocampus, microglia activation in the hippocampus was significantly alleviated compared with the surgery group. These results indicate that local OXT administration in the hippocampus can alleviate tibial fracture surgery-induced microglia activation in the hippocampus.

[0086] Example 4: Experiment on the effect of oxytocin on the PI3K / Akt / mTOR pathway in the hippocampus

[0087] I. Animal grouping and administration are the same as in Example 1.

[0088] II. Western blot detection of protein expression

[0089] Fresh hippocampal tissue was harvested from mice after anesthesia and placed in a 1.5 mL centrifuge tube with 150 μL of strong RIPA. The tissue was sonicated and allowed to stand on ice for 30 min. It was then centrifuged (13000 rpm) at 4°C for 15 min. After centrifugation, the supernatant was transferred to a new, pre-labeled 1.5 mL EP tube. Tissue protein quantification was performed using BCA, with 10 μL added to each well. Electrophoresis was performed at a constant voltage of 90 V for 120 min. PVDF membranes were cut to the same size as the separating gel and immersed in methanol for 30 s to fully activate them. Transfer was performed at a constant current of 350 mA for 120 min. Blocking was performed with 5% skim milk at room temperature for 1 h, or overnight at 4°C, followed by TBST washing three times (5 min each time). Primary antibody (1:200) was incubated at room temperature for 1 h, or overnight at 4°C, followed by TBST washing three times (5 min each time). Secondary antibody (1:2000) was incubated at room temperature for 1 h, followed by TBST washing three times (5 min each time). Add an appropriate amount of developer according to the size of the membrane, allow it to react for approximately 30 seconds, and then expose it. The exposure results are analyzed for grayscale using ImageJ software.

[0090] III. Experimental Results

[0091] like Figure 4 As shown in Figure D, in the aged mouse PND model, proteins related to the PI3K / Akt / mTOR pathway in the mouse hippocampus showed significant downregulation at both the mRNA and protein levels (P < 0.05). In the hippocampal local OTX administration group, the downregulation of p-PI3K, p-Akt, and p-mTOR at the mRNA level was significantly alleviated. This suggests that OTX administration can regulate the PI3K / Akt / mTOR signaling pathway.

[0092] Example 5: Experiment on the effect of oxytocin on mitochondrial morphology in hippocampal neurons

[0093] I. Animal grouping and administration are the same as in Example 1.

[0094] II. Electron microscopy examination of mitochondrial morphology and number in mouse hippocampal neurons

[0095] Mice were anesthetized and perfused, and the hippocampus was harvested. After fixation for 4 hours, the tissue was dehydrated with ethanol and propylene oxide, and then embedded in epoxy resin. Ultrathin sections with a thickness of 70 nm were prepared using an ultramicrotome. The sections were stained with lead citrate and uranyl acetate and then examined under an electron microscope.

[0096] III. Experimental Results

[0097] like Figure 5 As shown, electron microscopy revealed changes in the morphology of mitochondria within hippocampal neurons. Compared to the sham-operated group, mitochondria in hippocampal neurons showed significant swelling and shrinkage after PND in aged mice, indicating alterations and damage to the mitochondrial structure. Local administration of oxytocin to the hippocampus could partially alleviate the degree of mitochondrial swelling in hippocampal neurons, suggesting a protective effect of OTX on hippocampal neurons.

[0098] This invention established a postoperative cognitive impairment (PND) model in aged mice via tibial fracture surgery. RNAscope and qPCR experiments revealed an imbalance in the expression of OXT and OXTR in the hippocampus of PND mice. Local injection of OXT into the hippocampus to supplement OXT improved cognitive behavior in PND mice. Furthermore, OXT administration alleviated microglial activation and neuronal mitochondrial damage in the hippocampus of PND mice. In addition, oxytocin administration regulated the PI3K / Akt / mTOR signaling pathway in the hippocampus, which may be one of the mechanisms by which OXT alleviates cognitive impairment. These results demonstrate the definite efficacy of oxytocin in alleviating PND and provide insights for the development of targeted drugs to alleviate PND.

[0099] Based on the disclosure and teachings of the foregoing specification, those skilled in the art can make changes and modifications to the above embodiments. Therefore, the present invention is not limited to the specific embodiments disclosed and described above, and some modifications and changes to the present invention should also fall within the protection scope of the claims of the present invention. Furthermore, although some specific terms are used in this specification, these terms are only for convenience of explanation and do not constitute any limitation on the present invention.

Claims

1. Application of oxytocin in the preparation of drugs for the prevention and treatment of postoperative cognitive impairment.

2. The application according to claim 1, characterized in that: The medications for the prevention and treatment of postoperative cognitive impairment are administered topically to the hippocampus.

3. The application according to claim 1, characterized in that: The drugs mentioned above for the prevention and treatment of postoperative cognitive impairment can promote the expression of proteins related to the PI3K / Akt / mTOR pathway in the hippocampus.

4. The application according to claim 1, characterized in that: The medications mentioned above for the prevention and treatment of postoperative cognitive impairment can alleviate microglial cell activation in the hippocampus.

5. A drug for the prevention and treatment of postoperative cognitive impairment, characterized in that: The drug contains oxytocin.

6. The drug according to claim 5, characterized in that: The drug also includes pharmaceutically acceptable excipients, carriers, and / or diluents.

7. The drug according to claim 5, characterized in that: The concentration of oxytocin is 25 mg / L.

Images