Application of high taurine in inhibiting macrophage aging after spinal cord injury

Abstract

The invention discloses application of high taurine in inhibiting macrophage senescence after spinal cord injury. Comprising application of homotaurine in preparation of drugs for inhibiting aging of macrophages after spinal cord injury, drugs for inhibiting mitochondrial dysfunction of the macrophages after spinal cord injury, drugs for promoting repair of spinal cord injury, drugs for inhibiting neuroinflammation after spinal cord injury and drugs for increasing the expression quantity of SHMT2 protein in the macrophages. The invention relates to application of the compound in preparation of drugs for reducing mtDNA / cGAS / STING pathway activation in macrophages and drugs for reducing nuclear DNA damage mediated by reactive oxygen species in macrophages, in particular to application of the compound in preparation of drugs for reducing mtDNA / cGAS / STING pathway activation in macrophages. The invention reveals for the first time that high taurine significantly promotes spinal nerve regeneration, improves neurological functions, alleviates inflammatory response and protects spinal cord tissues by regulating immune cell mitochondrial metabolism-cell aging axis. The high taurine synergistically intervenes in secondary neurodegenerative diseases after spinal cord injury through a metabolism and immune dual-channel, and a brand new direction is provided for SCI treatment.

Description

Technical Field

[0001] The present invention relates to a new application of homotaurine, and in particular to the application of homotaurine in inhibiting the aging of macrophages after spinal cord injury. Background Art

[0002] Spinal cord injury (SCI) is a central nervous system disorder with a high disability rate. Its causes include traumatic injuries (such as car accidents and falls) and non-traumatic injuries (such as tumor compression and spinal cord ischemia). Its pathological process can be divided into two stages: primary injury and secondary injury. Primary injury mainly refers to neuronal axonal rupture, spinal cord hemorrhage, and blood-spinal cord barrier disruption caused by external forces; secondary injury is mainly characterized by a persistent inflammatory response, accompanied by changes such as cell apoptosis, glial scar formation, and mitochondrial dysfunction, ultimately leading to further deterioration of neurological function. Studies have shown that a large amount of lipid-rich myelin fragments can be released after spinal cord injury. These fragments are mainly phagocytosed by bone marrow-derived macrophages (BMDMs) to form foamy macrophages. The M2-like macrophages that originally exhibit anti-inflammatory and pro-repair properties are reversed to pro-inflammatory and pro-damage M1-like macrophages, amplifying the local inflammatory response and exacerbating neural tissue damage and dysfunction.

[0003] Current clinical treatments mainly include surgical decompression, glucocorticoid shock, and rehabilitation training, but there are still many limitations:

[0004] (1) Insufficient inflammation control: Traditional glucocorticoids have difficulty in specifically inhibiting inflammatory factors associated with aging of foamy macrophages, and long-term use can easily induce infection;

[0005] (2) Limitations of antioxidant effects: Existing antioxidants such as Edaravone mainly work by scavenging ROS and cannot effectively repair mitochondrial dysfunction;

[0006] (3) Nerve regeneration disorder: Neurotrophic factors (such as BDNF) are difficult to be effectively delivered under the scar barrier.

[0007] Tramiprosate (TMP) is a natural sulfur-containing amino acid derivative with excellent nervous system penetration and biosafety. This molecule is widely expressed in the central nervous system and has demonstrated significant protective effects in multiple neurodegenerative disease models. The mechanisms of action of homotaurine include:

[0008] (1) Neuroprotective effect: inhibiting abnormal aggregation of Tau protein, reducing β-amyloid protein, and reducing the production of NO;

[0009] (2) Metabolic support function: stimulating GABA type A receptors;

[0010] (3) Immunomodulatory ability: Increases serum IL-33 and IL-10 levels and decreases serum IL-18 levels.

[0011] However, there is currently a lack of systematic research revealing the mechanism of action of high taurine in targeting mitochondrial-induced cell aging after spinal cord injury, especially in regulating macrophage aging through mitochondrial NADPH metabolism (SHMT2-NADPH / GSH axis). Summary of the Invention

[0012] Purpose of the invention: The purpose of the present invention is to provide the use of high taurine in the preparation of drugs for inhibiting macrophage aging after spinal cord injury, drugs for inhibiting mitochondrial dysfunction of macrophages after spinal cord injury, drugs for promoting spinal cord injury repair, drugs for inhibiting neuroinflammation after spinal cord injury, drugs for increasing the expression of SHMT2 protein in macrophages, drugs for reducing the activation of the mtDNA / cGAS / STING pathway in macrophages, and drugs for reducing nuclear DNA damage mediated by reactive oxygen species in macrophages, so as to solve the problems of how to protect the mitochondrial function of immune cells after spinal cord injury, inhibit immune cell aging, inhibit spinal cord neuroinflammation and repair nerve damage.

[0013] Technical solution: The present invention first discloses the application of homotaurine in the preparation of drugs for inhibiting macrophage aging after spinal cord injury.

[0014] The structural formula of homotaurine (C3H9NO3S) described in the present invention is as follows:

[0015]

[0016] The second aspect of the present invention discloses the use of homotaurine in the preparation of a drug for inhibiting mitochondrial dysfunction of macrophages after spinal cord injury.

[0017] The third aspect of the present invention discloses the use of homotaurine in the preparation of a drug for promoting the repair of spinal cord injury.

[0018] The fourth aspect of the present invention discloses the use of homotaurine in the preparation of a drug for inhibiting neuroinflammation after spinal cord injury.

[0019] The present invention relates to the preparation of a medicine for treating spinal cord injury by protecting mitochondria and inhibiting cell aging, alleviating neuroinflammatory response, protecting nerve unit structure and promoting nerve function recovery.

[0020] Preferably, the spinal cord injury includes spinal cord injury-related neurological dysfunction and / or spinal cord injury-related peripheral nerve damage and nerve conduction disorders, such as paraplegia and motor loss caused by spinal cord injury. The spinal cord injury includes, but is not limited to, traumatic and non-traumatic injuries caused by trauma, traffic accidents, falls, sports injuries, or vascular diseases.

[0021] The fifth aspect of the present invention discloses the use of homotaurine in the preparation of a drug for increasing the expression of SHMT2 protein in macrophages.

[0022] The sixth aspect of the present invention discloses the use of homotaurine in the preparation of a drug for reducing the activation of the mtDNA / cGAS / STING pathway in macrophages.

[0023] The seventh aspect of the present invention discloses the use of homotaurine in the preparation of a drug for reducing nuclear DNA damage mediated by reactive oxygen species in macrophages.

[0024] Preferably, the macrophages are macrophages in a spinal cord injury site.

[0025] Preferably, the concentration of homotaurine in the drug is 2-200 μg / mL, and the purity of homotaurine is at least 99%.

[0026] The drug may also contain a pharmaceutically acceptable salt of homotaurine (such as sodium homotaurate), as well as pharmaceutically acceptable excipients (stabilizers, antioxidants, osmotic pressure regulators), etc. Pharmaceutical dosage forms include injections (intravenous / intrathecal), nanoparticle preparations (liposomes or recombinant keratin carriers), sustained-release gels, and oral tablets.

[0027] The high taurine in the present invention can protect mitochondrial function and enhance the antioxidant system by upregulating the expression of SHMT2 in macrophages at the site of spinal cord injury, reducing the activation of the mtDNA / cGAS / STING axis in macrophages and nuclear DNA damage mediated by reactive oxygen species, thereby inhibiting the occurrence of macrophage senescence after spinal cord injury and ultimately promoting the recovery of motor function after spinal cord injury.

[0028] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages:

[0029] This study reveals for the first time that high taurine significantly promotes spinal cord nerve regeneration, improves neurological function, reduces inflammation, and protects spinal cord tissue by regulating the immune cell mitochondrial metabolism-cell senescence axis, providing an innovative strategy for the treatment of spinal cord injury. High taurine synergistically intervenes in secondary neurodegeneration after spinal cord injury through both metabolic and immune pathways, offering a new direction for SCI treatment.

[0030] The present invention improves the ability to resist oxidative stress by activating mitochondrial NADPH metabolism (SHMT2-NADPH / GSH axis), reduces the activation of the cGAS / STING pathway caused by mtDNA leakage, protects mitochondrial function, and thereby inhibits the occurrence of macrophage aging; improves neurological function: enhances motor (BMS score), sensory and autonomic nervous function, and reduces demyelinating lesions; alleviates inflammatory response: inhibits secondary inflammatory response mediated by macrophage immune aging. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 The repair effect of high taurine on spinal cord injury;

[0032] Figure 2 Figure 1 is the results of WB and immunofluorescence detection of aging-related proteins;

[0033] Figure 3 This is the staining result of mouse spinal cord injury tissue;

[0034] Figure 4 These are the experimental results of primary bone marrow-derived macrophages;

[0035] Figure 5 The experimental results show that high taurine protects macrophage mitochondria and their functions after stimulation with myelin debris;

[0036] Among them, SCI represents spinal cord injury surgical modeling, sham represents sham operation, TMP represents high taurine administration, Ctrl represents blank control group, and MD Homo represents myelin fragment stimulation. DETAILED DESCRIPTION

[0037] The technical solution of the present invention will be further described below with reference to the accompanying drawings.

[0038] Example 1: Evaluation of the effect of high taurine on improving motor function and electrophysiological characteristics after spinal cord injury

[0039] The present invention aims to evaluate the effect of TMP on improving motor function and nerve conduction function in mice after spinal cord injury. The experimental results show that TMP can improve motor dysfunction and nerve conduction function after spinal cord injury.

[0040] Spinal cord injury can lead to interruption of spinal cord conduction function, resulting in motor and sensory dysfunction. The present invention establishes a C57BL / 6 mouse spinal cord injury model to simulate the pathological state of impaired neurological function after injury, and evaluates the role of high taurine in improving neurological function. The Basso Mouse Scale (BMS) scoring system is used to evaluate the motor behavior of mice. The BMS score is a quantitative indicator widely used in mouse SCI research. It is scored from 0 (complete paralysis) to 9 (normal movement) in a step-by-step manner, reflecting the motor coordination and weight-bearing gait ability of the test animals, which serves as the behavioral basis for neurological recovery.

[0041] Furthermore, the gastrocnemius compound muscle action potential (CMAP) is a classic electrophysiological indicator of neuromuscular conduction function. Its amplitude represents the number of muscle fibers recruited by excitation, reflecting the integrity and degree of recovery of the innervated muscle. Its latency represents the time required for the nerve impulse to travel from the stimulus site to the muscle, reflecting nerve conduction velocity and axonal function. By measuring changes in CMAP amplitude and latency, the degree of neuromuscular recovery can be objectively assessed.

[0042] To further explore the mechanism of action of hypertaurine, spinal cord tissue was obtained postoperatively for Western blot analysis to detect the expression of anti-inflammatory and aging-related proteins, and immunofluorescence analysis was used to assess changes in oxidative damage markers. Spinal cord tissue was also obtained for HE, LFB, and Nissl staining to assess tissue structure, myelin repair, and neuronal survival.

[0043] This study combined multiple evaluation methods to verify the neuroprotective effect and mechanism of high taurine after spinal cord injury through dual functional and structural evaluation. The specific experimental materials and methods are as follows:

[0044] 1. Experimental Animals

[0045] C57BL / 6 male mice (age: 8 weeks) were selected and randomly divided into sham operation group (Sham group), surgery group (SCI group) and high taurine intervention group (TMP group), with 10 mice in each group.

[0046] 2. Construction of Spinal Cord Injury Model

[0047] Based on our previous studies, we anesthetized mice with an intraperitoneal injection of tribromoethanol, disinfected their skin with iodine, and then exposed their spinal cords at T10. A 5-gram spinal cord impactor (RWD, Shenzhen, China) was used to impact their spinal cords from a height of 5 cm. Successful SCI modeling was established when the mice developed spinal cord hematoma, tail flicking, and hindlimb paralysis.

[0048] 3. Drug treatment

[0049] TMP group was given intraperitoneal injection of high taurine saline solution within 24 hours after surgery, with a dose of 25, 50 mg / kg (depending on the group), once a day for 28 consecutive days; Sham group and SCI model group were given equal volume of saline.

[0050] Homotaurine was purchased from a regular MCE drug supplier, and reagents such as normal saline were purchased from qualified suppliers.

[0051] 4. Post-test processing

[0052] 1) Motor function assessment

[0053] The BMS scoring method was used to evaluate the recovery of hind limb motor function of mice on days 1, 7, 14, 21, and 28 after surgery. Figure 1 As shown in Figure B, the BMS score of the TMP group was significantly higher than that of the SCI group from the 7th day, and the difference was statistically significant on the 28th day (P<0.01), suggesting that high taurine can promote the recovery of motor function.

[0054] 2) BMS score

[0055] The BMS scoring system was used to evaluate the changes in hind limb function in mice after spinal cord injury. The hind limb ankle joint range of motion, coordination, paw posture, trunk stability, and tail posture of the mice were scored 1, 3, 7, 14, 21, and 28 days after spinal cord injury. Figure 1 As shown in Figure A, the scores of mice in the TMP group were significantly better than those in the SCI group from day 7 to day 28, and the difference was statistically significant (P<0.05).

[0056] 3) Electrophysiological testing

[0057] On the 28th day after spinal cord injury, the compound muscle action potential (CMAP) parameters evoked by the gastrocnemius muscle were measured using an electromyograph. During the operation, the stimulating electrode was placed on the upper edge of the injured spinal cord segment and the recording electrode was placed on the belly of the gastrocnemius muscle. Figure 1 As shown in Figure C.

[0058] 4) Tissue collection and testing

[0059] After the test, tissue was collected and Western blot analysis was performed on the lesion tissue to detect aging-related proteins (such as p53, p21, and γH2A.X). At the same time, immunofluorescence analysis was performed to evaluate the expression of serine hydroxymethyltransferase-2 (SHMT2) and to observe changes in DNA oxidative damage markers 8-hydroxydeoxyguanosine (8-OHDG) and cyclic guanosine monophosphate-adenylate synthetase (cGAS). The results are as follows: Figure 2 As shown in Figure A.

[0060] To evaluate the effects of high taurine on spinal cord tissue damage and neuroprotection, spinal cord tissues of mice in each group were subjected to HE, LFB, and Nissl staining. HE staining was used to observe tissue structural integrity; LFB staining was used to assess the loss and repair of myelin sheaths; and Nissl staining was used to assess neuronal survival. Figure 2 As shown in Figure B.

[0061] 5. Experimental results

[0062] Figure 1 Figure 1 shows the repair effect of hypertaurine on spinal cord injury. Figure A shows the BMS scores, showing that mice in the TMP group showed significantly higher motor function scores than those in the SCI group from day 7 to day 28 after injury. The difference was statistically significant (P < 0.05), indicating that hypertaurine can effectively promote motor function recovery in mice after spinal cord injury, improving motor coordination and weight-bearing gait ability. Figure B shows the gait analysis results, showing that the TMP group showed significantly improved gait recovery compared to the SCI group on day 21. Gait parameters such as stride length and stride width showed significant improvements, indicating that the hypertaurine-treated group significantly outperformed the untreated group in motor recovery, including gait coordination. Figure C shows the electrophysiological test results, showing that the compound muscle action potential (CMAP) amplitude of the gastrocnemius muscles in the TMP group was significantly increased, and the latency was significantly shortened (P < 0.05). Compared with the SCI group, this indicates a significant improvement in nerve conduction function, indicating that hypertaurine can effectively promote the recovery of nerve conduction function and improve the efficiency of nerve conduction after spinal cord injury.

[0063] Figure 2 Figures 2 and 3 are the results of Western blot and immunofluorescence analysis of senescence-related proteins. Figure A shows the Western blot results, which show that the expression levels of senescence-related proteins p53 and p21 in the TMP group were significantly lower than those in the SCI group. This indicates that hypertaurine significantly reduced the expression of senescence-related markers such as p53, p21, and γH2A.X in the spinal cords of SCI mice (P<0.05), further confirming the role of hypertaurine in inhibiting cellular senescence after spinal cord injury. Figure B shows the results of immunofluorescence analysis, which show that the TMP group significantly increased SHMT2 expression and significantly decreased 8-OHDG expression in macrophages after spinal cord injury (P<0.05), suggesting that hypertaurine plays an important role in reducing DNA oxidative damage. The decreased expression of cGAS suggests that this pathway may be involved in inhibiting macrophage immunosenescence. Figure 2 The results showed that high taurine can protect mitochondrial function by regulating metabolism, thereby reducing oxidative stress and inhibiting cell senescence mediated by cGAS pathway activation, which is conducive to the repair of spinal cord injury.

[0064] Figure 3Figure 1 shows the staining results of spinal cord injury tissue in mice. Figure A shows the HE staining results, which show that the spinal cord injury area of ​​the SCI group mice was significantly damaged, while the high taurine treatment group significantly improved the tissue structure, with the tissue morphology closer to normal and the degree of inflammation reduced. Figure B shows the LFB staining results, which show that the myelin staining in the SCI group became significantly lighter, indicating severe demyelination, while high taurine treatment can significantly improve the myelin structure, enhance the staining intensity, and preserve the myelin structure well, suggesting that it has the effect of promoting myelin repair. Figure C shows the Nissl staining results, which show that the number of neurons in the SCI group was significantly reduced and the cell outlines were unclear, while the number of neurons in the high taurine group increased, the morphology was intact, and the neuronal survival rate was significantly improved, suggesting that it has a good neuroprotective effect in protecting neurons. Figure 3 Scale bar = 100 μm.

[0065] Figure 1-3 The results showed that high taurine can significantly improve the nerve conduction efficiency and motor function of mice after SCI, and exert neuroprotective effects by regulating redox capacity and inhibiting aging, providing an experimental basis for subsequent mechanism research and drug development.

[0066] Example 2: Experiment on the protection of mitochondrial function of macrophages after myelin stimulation, anti-oxidative stress and inhibition of macrophage aging by high taurine

[0067] This study aimed to investigate the neuroprotective mechanisms of hypertaurine after spinal cord injury. Using an in vitro model, primary bone marrow-derived macrophages were stimulated with myelin fragments to analyze the role of hypertaurine in regulating the injury microenvironment. The results demonstrated that hypertaurine inhibited the senescence-mediated inflammatory response in macrophages following myelin stimulation.

[0068] Lipid accumulation in macrophages impairs mitochondrial function, leading to the generation of large amounts of mitochondrial reactive oxygen species (mtROS) and the release of mtDNA. As an innate immune activation signal, mtDNA induces cellular senescence by activating the cGAS-STING pathway. Excessive mtROS production causes oxidative damage to nuclear DNA, facilitating cellular senescence and ultimately leading to the sustained release of SASPs such as IL-6 and TNF-α.

[0069] When macrophages engulf large amounts of myelin debris, they trigger mitochondrial dysfunction. This, on the one hand, causes mtDNA leakage and triggers activation of the cGAS / STING axis, and on the other hand, generates a large amount of ROS-mediated oxidative damage to nuclear DNA, ultimately leading to macrophage senescence. This event, in combination, promotes neuronal apoptosis and further deteriorates neurological function.

[0070] This study used an in vitro model to explore the effects of high taurine on aging markers, mitochondrial function, and other factors, revealing its neuroprotective mechanism after spinal cord injury. The specific experimental materials and methods are as follows:

[0071] 1. Experimental cells

[0072] Primary bone marrow-derived macrophages were obtained from normal mice (C57BL / 6, 8 weeks old, weighing 20 ± 2 g). All cells were cultured under standard conditions.

[0073] 2. Extraction of myelin fragments

[0074] According to previous literature, 8-week-old mice were sacrificed and their brains removed. The brains were then homogenized in a 0.32 M sucrose solution and slowly added to a 0.83 M sucrose solution for centrifugation using a sucrose density gradient. After centrifugation at 100,000 × g for 45 minutes at 4°C, myelin fragments were collected from the interface between the two sucrose densities. The fragments were weighed and resuspended in sterile PBS to a 100 mg / ml myelin homogenate.

[0075] 3. Myelin fragment stimulation model

[0076] Myelin fragments were extracted from the brains of 8-week-old mice using a sucrose concentration gradient method. Primary bone marrow-derived macrophages were stimulated with myelin fragments at a final concentration of 1 mg / mL. Primary bone marrow-derived macrophages were divided into the following groups:

[0077] 1) Control group: no stimulation or drug treatment;

[0078] 2) Stimulation group: only 1 mg / 1 ml myelin fragment stimulation, no intervention;

[0079] 3) Low-dose high-taurine group: BMDMs were pretreated with 2 μg / mL high-taurine for 2 hours and then myelin debris was added;

[0080] 4) Medium-dose high-taurine group: BMDMs were pretreated with 20 μg / mL high-taurine for 2 hours, and then myelin debris was added;

[0081] 5) High-dose high-taurine group: BMDMs were pretreated with 200 μg / mL high-taurine for 2 hours, and then myelin debris was added.

[0082] 3. Post-test processing

[0083] 24 hours after stimulation, cells were collected for the following experimental analysis.

[0084] 1) Western blot analysis

[0085] Immunoblotting was performed to examine the expression levels of proteins associated with senescence, inflammation, and oxidative stress in macrophages stimulated with myelin debris using the following antibodies: senescence markers: p53 and p21; DNA damage marker: γH2A.X; and internal control protein: β-actin. Grayscale values ​​of protein bands were analyzed using ImageJ software.

[0086] 2) qPCR analysis

[0087] qPCR was used to detect the expression level of SASP factors to further verify the role of high taurine in regulating the inflammatory microenvironment.

[0088] 3) Confocal JC-1 staining

[0089] The changes in mitochondrial membrane potential were observed by confocal microscopy to evaluate the regulatory effect of high taurine on mitochondrial function. 4) Flow cytometry was used to detect the level of oxidative stress.

[0090] Flow cytometry was used to detect mitoSOX levels in primary macrophages treated with myelin debris to assess changes in oxidative stress.

[0091] 5) Detection of NADPH expression using a microplate reader

[0092] The expression of NADPH in primary macrophages was detected using a microplate reader to evaluate the redox capacity of the cells.

[0093] 4. Experimental results

[0094] Figure 4Figure 1 shows the results of an experiment using primary bone marrow-derived macrophages. Figure A shows the effects of different TMP concentrations on the expression of inflammatory and senescence markers in primary macrophages stimulated by myelin debris. Western blot analysis of the expression of senescence markers p53, p21, and γH2A.X revealed a significant upregulation of senescence markers in model mice following myelin debris stimulation. Compared with the SCI group, the high-taurine treatment groups (2, 20, and 200 μg / mL increasing concentrations) significantly reduced the expression of these markers, particularly in the high-dose group (200 μg / mL), with statistically significant differences (P < 0.05). WB strips showed that high taurine significantly inhibited the expression of inflammation and aging indicators after spinal cord injury; Figure B is the result of the immunofluorescence experiment, which shows that high taurine increased the expression of SHMT2 and reduced the expression of 8OHDG, a marker of DNA oxidative damage in macrophages; Figure C is the result of qPCR detection, which shows the expression of SASP factors in macrophages of each group. The results showed that myelin fragments stimulated a significant increase in SASP factors such as IL-6, IL-1β and TNF-α in macrophages. The high taurine treatment groups (low, medium and high doses) showed a significant downregulation of SASP factors, especially the high dose group (200μg / mL), which showed a more significant inhibitory effect. High taurine treatment significantly inhibited the upregulation of inflammation-related SASP factor mRNA levels, further supporting the potential role of high taurine in alleviating inflammatory responses.

[0095] Figure 5Figure 1 shows experimental results demonstrating that high taurine protects mitochondria and their function in macrophages stimulated with myelin debris. Panel A shows JC-1 confocal staining, which reveals a significant decrease in mitochondrial membrane potential (red / green fluorescence ratio) in macrophages stimulated with myelin debris, suggesting impaired mitochondrial function. However, high taurine treatment significantly restored membrane potential, suggesting a positive role in maintaining mitochondrial function. Panel B shows flow cytometry analysis of oxidative stress, using MitoSOX as a marker of oxidative stress. Upon stimulation with myelin debris, oxidative stress levels in the model macrophages increased significantly, with increased MitoSOX signal intensity, indicating elevated levels of reactive oxygen species (ROS). The high-dose group (200 μg / mL) and high-taurine treatment group showed a significant decrease in MitoSOX signal intensity, indicating that high taurine significantly inhibited the mitochondrial reactive oxygen level of primary bone marrow-derived macrophages treated with myelin fragments, and could effectively inhibit the oxidative stress generated after spinal cord injury and reduce oxidative damage; Figure C is a mitochondrial image taken by electron microscopy of macrophages, which shows that under myelin stimulation, mitochondria are damaged, specifically manifested in unclear mitochondrial structure, broken or even disappeared cristae, while the mitochondrial morphology and structure of the high-taurine treatment group are normal, and the number of mitochondrial cristae is greater than that of the myelin stimulation group, indicating that high taurine protects the mitochondrial structure and increases the number of mitochondrial cristae; Figure D is the result of NADPH expression detected by microplate reader. The NADPH value of macrophages decreased significantly after myelin stimulation, while high taurine significantly increased the expression of NADPH in macrophages; Figure E is the result of mtDNA detection, which shows that high taurine significantly reduced the leakage of mtDNA in macrophages after myelin stimulation.

[0096] In summary, high taurine improves the pathological microenvironment after spinal cord injury through multiple synergistic effects, protects mitochondrial function through SHMT2, reduces the activation of the cGAS pathway, and inhibits the inflammatory response mediated by macrophage immunosenescence, thereby exerting a neuroprotective effect. This provides experimental basis and theoretical support for its subsequent development as a drug for the treatment of spinal cord injury.

Claims

1. Application of homotaurine in the preparation of drugs for inhibiting macrophage senescence after spinal cord injury.

2. Application of homotaurine in the preparation of drugs for inhibiting mitochondrial dysfunction of macrophages after spinal cord injury.

3. Application of homotaurine in the preparation of drugs to promote the repair of spinal cord injury.

4. Application of homotaurine in the preparation of drugs for inhibiting neuroinflammation after spinal cord injury.

5. The use according to any one of claims 1 to 4, characterized in that The spinal cord injury includes spinal cord injury-related neurological dysfunction and / or spinal cord injury-related peripheral nerve damage and nerve conduction disorder.

6. Application of homotaurine in the preparation of drugs to increase the expression of SHMT2 protein in macrophages.

7. Application of homotaurine in the preparation of drugs to reduce the activation of the mtDNA / cGAS / STING pathway in macrophages.

8. Use of homotaurine in the preparation of drugs for reducing nuclear DNA damage mediated by reactive oxygen species in macrophages.

9. The use according to any one of claims 6 to 8, characterized in that: The macrophages are macrophages in the spinal cord injury site.

10. The use according to any one of claims 1-4 and 6-8, characterized in that The concentration of homotaurine in the medicine is 2-200 μg / mL.

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