Application of halofuginone in medicine for treating spinal cord injury

Abstract

The invention relates to the technical field of biological medicine, in particular to application of halofuginone in medicine for treating spinal cord injury. The invention provides application of halofuginone in preparation of a medicine for treating spinal cord injury, application of halofuginone in preparation of a medicine for promoting spinal cord injury repair and application of halofuginone in preparation of a medicine for promoting exercise ability recovery after spinal cord injury. The therapeutic drug can promote functional recovery after spinal cord injury, inhibit activation of microglial cells after spinal cord injury and reduce inflammatory response. In addition, the treatment medicine can prevent neuronal reduction after spinal cord injury.

Description

Technical Field

[0001] The invention relates to the technical field of biomedicine, and in particular to the application of halofuginone in medicines for treating spinal cord injury. Background Art

[0002] Spinal cord injury is a serious disease that may lead to irreversible neurological function loss. Although many diseases are gradually being effectively treated with the continuous advancement of medical technology, spinal cord injury has long been a complex problem that has yet to be solved. According to its pathogenesis, spinal cord injury can be divided into two categories: traumatic and non-traumatic. Traumatic spinal cord injury is usually caused by spinal fractures, such as traffic accidents or other accidental injuries. Non-traumatic spinal cord injury is mainly caused by internal factors such as tumors, inflammation or infection. The pathological process of spinal cord injury mainly includes primary injury and secondary injury. Primary injury is caused by neuronal loss, while secondary injury further aggravates tissue damage and hinders recovery, among which inflammatory response is an important secondary factor. Therefore, the current drug treatment for spinal cord injury focuses mainly on anti-inflammatory and neuroprotection. Despite some progress, the challenges are still huge, and no drug has been officially approved to treat this disease so far.

[0003] Halofuginone is a halogenated derivative of febrifugine, an alkaloid isolated and obtained from the plant Dichroa febrifuga. The molecular formula of halofuginone is C 16 H 17 BrClN3O3 is a white or light gray crystalline powder, odorless and bitter. The earliest research on halofuginone began in 1975, and it has been used as a broad-spectrum anticoccidial drug for a long time. In recent years, with the in-depth research on halofuginone, it has been found that halofuginone can promote wound repair, inhibit tissue fibrosis and fight tumors. However, there is no report on the use of halofuginone in the treatment of spinal cord injury. Summary of the invention

[0004] In view of this, in order to at least partially solve the above problems, the present invention provides the use of halofuginone in the preparation of a medicament for treating spinal cord injury.

[0005] In one aspect, the present invention relates to the use of halofuginone in preparing a medicament for treating spinal cord injury.

[0006] In some embodiments, the spinal cord injury is a traumatic spinal cord injury and a non-traumatic spinal cord injury.

[0007] In another aspect, the present invention relates to the use of halofuginone in preparing a medicament for promoting the repair of spinal cord injury.

[0008] In some embodiments, the spinal cord injury repair includes restoration of motor function.

[0009] In still another aspect, the present invention relates to the use of halofuginone in the preparation of a medicament for promoting recovery of motor ability after spinal cord injury.

[0010] In some embodiments, the restored motor ability is manifested as an increase in motor ability.

[0011] Optionally, the medicament further comprises a pharmaceutically acceptable carrier or excipient.

[0012] Optionally, the drug is an oral preparation or an injection.

[0013] Beneficial technical effects

[0014] The therapeutic drug of the present invention has a very excellent therapeutic effect on spinal cord injury. The therapeutic drug of the present invention can promote functional recovery after spinal cord injury. The therapeutic drug of the present invention can inhibit the activation of microglia after spinal cord injury and reduce inflammatory response. Moreover, the therapeutic drug of the present invention can protect the reduction of neurons after spinal cord injury. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 The BBB scores were expressed after administration of 50 μg / kg and 250 μg / kg of halofuginose for one week immediately after spinal cord injury.

[0016] Figure 2 The graphs show the results of a grid experiment after administration of 50 μg / kg and 250 μg / kg of halofuginose for one week immediately after spinal cord injury.

[0017] Figure 3 The swimming test scores were obtained after administration of 50 μg / kg and 250 μg / kg of halofuginose for one week immediately after spinal cord injury.

[0018] Figure 4 To represent the hot plate test score after administration of 50 μg / kg and 250 μg / kg of halofuginose for one week immediately after spinal cord injury.

[0019] Figure 5 Catwalk footprints (A) and statistical data (B and C) after administration of 50 μg / kg and 250 μg / kg of halofuginose for one week immediately after spinal cord injury.

[0020] Figure 6 This is an immunofluorescence image of tissues after administration of 250 μg / kg of halofuginose for one week immediately after spinal cord injury. The red color is glial fibrillary acid protein and the blue color is 4′,6-diamidino-2-phenylindole.

[0021] Figure 7This is an immunofluorescence image of tissues after administration of 250 μg / kg of halofuginose for one week immediately after spinal cord injury. The red color is glial fibrillary acid protein, the blue color is 4′,6-diamidino-2-phenylindole, and the green color is ionized calcium binding adaptor molecule 1.

[0022] Figure 8 This is an immunofluorescence image of tissues after administration of 250 μg / kg of halofuginose for one week immediately after spinal cord injury. The red color represents neuronal nuclear antigen and the blue color represents 4′,6-diamidino-2-phenylindole.

[0023] Fig. 9 The KEGG enrichment results of the spinal cord injury group and the treatment group were detected by RNA sequencing after the animals were given 250 μg / kg of fufuxin for one week immediately after spinal cord injury. DETAILED DESCRIPTION

[0024] In order to make the purpose, technical scheme and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with specific embodiments and with reference to the accompanying drawings. The embodiments provided below can be used as a guide for further improvements by ordinary technicians in the field and do not constitute a limitation of the present invention in any way.

[0025] The experimental methods in the following examples, unless otherwise specified, are all conventional methods, and are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. The materials, reagents, etc. used in the following examples, unless otherwise specified, can all be obtained from commercial channels.

[0026] Experimental animals

[0027] The experimental animals used in this experiment were Wistar female rats (8–10 weeks old, weighing 180–220 g), purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd. All experimental animals met the relevant national standards for the use and care of experimental animals. Rat housing conditions: The experimental rats were kept in an animal room with an ambient temperature of 22±2°C and a 12-h light-dark cycle (lighting time was 7 am to 7 pm). Rats were free to take standard pellet feed and water, and were adaptively fed for at least 7 days before the experiment.

[0028] Main reagents and instruments

[0029] Source of reagents:

[0030] Halofuginone: purchased from MCE, purity ≥99%.

[0031] Iba-1 antibody: purchased from Abcam (Cat. No. ab178847).

[0032] GFAP antibody: purchased from Abcam (Cat. No. ab7260).

[0033] DAPI dye: purchased from Abcam.

[0034] Instrument source:

[0035] Fluorescence microscopy: Images were acquired using an Olympus laser confocal microscope.

[0036] Spinal cord injury modeling apparatus: NYU Impact-III spinal cord injury modeling apparatus (USA) was used.

[0037] Cryostat: Leica CM3050S was used to prepare tissue sections.

[0038] Statistical methods

[0039] All experimental data are expressed as mean ± standard error (Mean ± SEM). Data analysis was performed using SPSS26.0 statistical software. The specific method is as follows:

[0040] 1. Comparison between groups

[0041] When the experimental data were normally distributed and met the homogeneity of variance, one-way ANOVA was used for inter-group comparison, and Tukey's HSD test was used for multiple comparisons after significance test.

[0042] If the data did not meet the normal distribution or homogeneity of variance, the Kruskal-Wallis nonparametric test was used.

[0043] 2. Comparison between the two groups

[0044] When only two groups of data need to be compared, the independent sample t-test is used.

[0045] For non-normally distributed data, the Mann-Whitney U test was used.

[0046] 3. Repeated measures data

[0047] Repeated measures ANOVA was used to analyze behavioral scores that changed over time (such as BMS scores and CatWalk analysis).

[0048] 4. Correlation Analysis

[0049] Pearson correlation analysis was used to evaluate the linear relationship between normal data. For non-normal data, Spearman rank correlation analysis was used.

[0050] 5. Significance level

[0051] The significance threshold was set at P < 0.05, and the results are expressed as follows:

[0052] P ≤ 0.05 (significant, *)

[0053] P ≤ 0.01 (highly significant, **)

[0054] P ≤ 0.001 (very significant, ***)

[0055] All experiments were repeated three times (n ≥ 3), and the specific sample size was calculated based on power analysis to ensure the reliability of the statistical results.

[0056] Example 1: Establishment of rat spinal cord injury animal model and BBB scoring

[0057] The IMPACTOR MODEL-Ⅲ spinal cord injury impact system was used to establish an acute spinal cord injury experimental animal model. Female Wistar rats aged 6-8 weeks and weighing 200g were selected. Twenty-four rats were divided into four groups, with 6 rats in each group, namely the sham operation group (only T10 laminectomy without impact), the control group (spinal cord injury group), the low-dose treatment group (50μg / kg body weight) and the high-dose treatment group (250μg / kg body weight). After the rats were anesthetized, the 10th thoracic vertebral lamina was surgically removed to expose the corresponding segment of the spinal cord, which was fixed under the impact device. The impact force was a 10g weight with a diameter of 2.5mm and a drop from a height of 25mm (10g×25mm). After the impact, the injured spinal cord was locally congested and edematous, the rat's hind limbs briefly spasmed and twitched, and after the tail swung, both lower limbs were paralyzed. The BBB score was 0 on the day after the injury, indicating that the impact model was successfully established. The drug was injected into the rats of the treatment group once a day at a dose of 50 μg / kg body weight and 250 μg / kg body weight starting from the first day after the impact injury for one week.

[0058] The BBB score is currently one of the internationally recognized objective standards for evaluating neurological function after spinal cord injury in rats. This project adopted a double-blind, two-person independent observation and recording, and finally statistical analysis to evaluate the motor function of the rat hind limbs from 1 day to 6 weeks after injury (Basso, DM, Beattie, MS, & Bresnahan, JC (1995). A sensitive and reliable locomotor rating scale for open field testing in rats. Journal of neurotrauma, 12(1), 1–21. https: / / doi.org / 10.1089 / neu.1995.12.1IF: 3.9 Q1). The BBB scoring items are shown in the following table.

[0059] Figure 1 The BBB scores of each group at different times after injury are shown in Figure 3. Three weeks after injury, there was a significant statistical difference between the treatment group and the injury group (p < 0.05);

[0060] Example 2. Evaluation of hind limb motor function of experimental animals using a grid test

[0061] The rat grid test is a commonly used experimental method to evaluate the recovery of sensory and motor function in rats after spinal cord injury. In this experiment, rats are trained to walk on a grid. The motor function is evaluated by observing the rats' ability to walk on the grid and mainly evaluating the ratio of the number of wrong or empty steps of their hind limbs to the total number of steps. This project uses double-blind, three-person independent observation and recording, and finally statistical analysis to evaluate the motor function of the rats' hind limbs 6 weeks after injury.

[0062] Figure 2 The gait error rate (% of errors / steps) of different experimental groups in the grid test is shown to evaluate the recovery of motor function after spinal cord injury. Data are expressed as mean ± standard error (Mean ± SEM), and significant differences are analyzed by one-way ANOVA and Tukey post hoc test, with significance levels of *p < 0.05 and ****p < 0.0001.

[0063] The specific results are as follows:

[0064] In the sham group (Sham), the gait error rate was close to 0%, indicating that the motor function of the hind limbs of normal rats was intact and there were no gait errors.

[0065] In the spinal cord injury group (Injury), the gait error rate was significantly higher than that in the sham operation group (p < 0.0001), and the error rate was about 70%, indicating that spinal cord injury significantly affected the motor function of the hind limbs.

[0066] In the low-dose treatment group (H 50 μg / kg), low-dose halofuginone treatment significantly reduced the gait error rate (about 50%), which was significantly different from the spinal cord injury group (p < 0.05). However, there was still a higher gait error rate compared with the high-dose treatment group, indicating that low-dose treatment improved motor function to a certain extent, but the effect was limited.

[0067] In the high-dose treatment group (H 250 μg / kg), the gait error rate was further reduced to approximately 30%, which was highly significantly different from the spinal cord injury group (p < 0.0001) and also significantly different from the low-dose group (p < 0.05).

[0068] Conclusion: High-dose halofuginone (H 250 μg / kg) significantly outperformed the untreated group (Injury) in the recovery of motor function after spinal cord injury, as shown by a significant reduction in gait error rate. This suggests that halofuginone at high doses may promote neural repair and motor function recovery after spinal cord injury through a more effective mechanism.

[0069] Example 3. Evaluation of hind limb motor function of experimental animals using swimming test

[0070] The rat swimming test is a commonly used hind limb motor behavior assessment method used to evaluate the motor function and coordination ability of rats after spinal cord injury. In this experiment, the recovery of motor function and coordination ability of rats is evaluated by observing their swimming performance in water. At week 6 after injury, the rats were placed in a pool to observe their swimming posture, speed and coordination ability, and the swimming performance of the rats in water was recorded, including indicators such as swimming speed, swimming posture and coordination ability. This project adopted double-blind, two-person independent observation and recording. The specific scoring criteria are shown in the following table. Finally, statistical analysis was performed to evaluate the motor function of the hind limbs of rats at week 6 after injury.

[0071]

[0072] Figure 3 The results of the swimming test scores of different experimental groups after spinal cord injury are shown, which are used to measure the degree of motor and sensory recovery after spinal cord injury in rats. The higher the swimming test score, the better the recovery of motor and sensory function. The specific results are as follows:

[0073] The LSS score of the sham group was about 18 points, indicating that the motor and sensory functions of the undamaged rats were normal.

[0074] The LSS score of the spinal cord injury group (Injury group) was significantly lower than that of the Sham group (p < 0.001), about 7 points, indicating that spinal cord injury significantly reduced the motor and sensory functions of rats.

[0075] The LSS score of the low-dose treatment group (H 50 μg / kg group) was slightly improved (about 10 points) compared with the Injury group, but it did not reach the statistically significant level, indicating that low-dose halofuginone has limited improvement on motor and sensory functions.

[0076] The LSS score of the high-dose treatment group (H 250 μg / kg group) was significantly higher than that of the Injury group (p < 0.01), reaching about 14 points, close to the level of the Sham group, indicating that high-dose halofuginose has a significant effect in promoting the recovery of motor and sensory functions.

[0077] In summary, high-dose fufuginone significantly improved the motor function of rats after spinal cord injury, and its effect was better than low-dose treatment, suggesting the dose-dependent effect of fufuginone and its potential application value in the treatment of spinal cord injury.

[0078] Example 4. Evaluation of hind limb motor function of experimental animals using hot plate test

[0079] The rat hot plate test is a commonly used experimental method to evaluate the pain perception and conduction of rats after spinal cord injury. In this experiment, the changes in pain perception and conduction are evaluated by observing the reaction time of rats on the hot plate. The rats were placed on a hot plate with a preset temperature of 52°C, and the reaction time of each rat was observed, including reactions such as licking the feet, jumping or scratching the feet, to evaluate their pain perception and conduction. This project used double-blind, two-person independent observation and recording, and finally statistical analysis to evaluate the pain sensory function of the rats' hind limbs at week 6 after injury.

[0080] Figure 4 The time required for the first pain response in each experimental group in the tactile pain response experiment (Time for first reaction, seconds) is shown. The longer the time, the lower the pain sensitivity; the shorter the time, the higher the pain sensitivity.

[0081] The first pain reaction time of the sham group (Sham group) was the longest, about 18 seconds, indicating that normal rats have the lowest pain sensitivity. The first pain reaction time of the spinal cord injury group (Injury group) was significantly lower than that of the Sham group (p < 0.001), about 5 seconds, indicating that spinal cord injury significantly enhanced the pain sensitivity of rats. The first pain reaction time of the low-dose treatment group (H 50 μg / kg group) was longer than that of the Injury group, about 8 seconds, but it did not reach a statistically significant level compared with the Injury group, indicating that the effect of low-dose treatment on reducing pain sensitivity was limited. The first pain reaction time of the high-dose treatment group (H 250 μg / kg group) was significantly prolonged, about 12 seconds, which was highly significantly different from the Injury group (p < 0.001). Compared with the low-dose group, the high-dose group had a more significant effect on reducing pain sensitivity, but it was still lower than the level of the Sham group.

[0082] in conclusion:

[0083] The tactile pain response experiment showed that spinal cord injury significantly enhanced pain sensitivity, and high-dose halofuginone (H250 μg / kg) could significantly prolong the first pain reaction time and reduce pain sensitivity, and its effect was better than low-dose treatment (H50 μg / kg). This suggests that high-dose halofuginone has the potential value in alleviating pain sensitivity associated with spinal cord injury.

[0084] Example 5. Evaluation of hind limb motor function of experimental animals using the Catwalk test

[0085] The rat Catwalk experiment is a commonly used gait analysis method used to evaluate the gait function and motor ability of rats after spinal cord injury. The Catwalk system is a high-resolution gait analysis system that can record the plantar imprints of rats in real time when they walk on a transparent glass plate, thereby evaluating gait characteristics and gait parameters. At week 6 after injury, rats in each experimental group were placed on the Catwalk system and allowed to walk freely. The system would record the plantar imprints and gait characteristics of the rats in real time. The gait parameters of the rats, including gait cycle, stride, support time and other indicators, were analyzed using the software provided by the Catwalk system to evaluate the gait function and motor ability of the rats. This project used double-blind, two-person independent observation and recording, and finally statistical analysis to evaluate the hind limb motor function of rats at week 6 after injury.

[0086] Figure 5Figure 2 shows the gait characteristics of different experimental groups in the gait analysis experiment (CatWalk), including the comparison of gait trajectory graph (A), regularity index (%) (B) and stride length (cm) (C), which are used to evaluate motor coordination and gait recovery after spinal cord injury.

[0087] Combination Figure 5 The results shown in A in Figure 1 are used to analyze the gait trajectory:

[0088] In the sham operation group (Sham group), the gait trajectory was clear and regular, and the gait coordination of the four limbs was good.

[0089] In the spinal cord injury group (Injury group), the trajectory was disordered, the gait was obviously irregular, and the coordination of the hind limb gait was significantly reduced, indicating that spinal cord injury seriously affected the motor ability of rats.

[0090] In the low-dose halofuginose-treated group (H 50 μg / kg group), the gait trajectory was slightly improved compared with the Injury group, but there was still obvious irregularity, and the improvement of hindlimb gait coordination was limited.

[0091] The gait trajectory of the high-dose halofuginose group (H 250 μg / kg group) was close to that of the Sham group, and the gait regularity was significantly improved, indicating that high-dose halofuginose has a significant effect on gait recovery after spinal cord injury.

[0092] Figure 5 B in the figure shows the Regularity Index (%) of each experimental group. In the Sham group, the Regularity Index was close to 100%, indicating that the coordination of limb movements was completely normal. In the Injury group, the Regularity Index dropped significantly to about 50%, which was significantly different from the Sham group (****p < 0.0001), indicating that spinal cord injury severely damaged the coordination of movements.

[0093] In the H 50 μg / kg group, the regularity index was slightly higher than that in the Injury group, about 65%, but there was still a significant difference compared with the Sham group (***p < 0.001), and the improvement effect was limited. In the H 250 μg / kg group, the regularity index was significantly increased to about 80%, which was significantly different from the Injury group (****p < 0.0001), close to the level of the Sham group, indicating that high-dose halofuginone significantly improved motor coordination.

[0094] Figure 5C in the figure shows the stride length (Stride Length, cm) of each experimental group. Among them, the stride length in the Sham group was the largest, about 12 cm, indicating normal motor function. In the Injury group, the stride length was significantly shortened to about 5 cm, which was significantly different from the Sham group (****p < 0.0001). In the H 50 μg / kg group, the stride length increased to about 8 cm, which was significantly different from the Injury group (*p < 0.05), but there was still a large gap compared with the Sham group. In the H 250 μg / kg group, the stride length further increased to about 10 cm, which was significantly different from both the Injury group and the H 50 μg / kg group (****p < 0.0001 and *p < 0.05), approaching the level of the Sham group.

[0095] Overall conclusion: Gait analysis results showed that spinal cord injury significantly reduced the motor coordination (regularity index) and stride length of rats, while halofuginone treatment was able to improve these indicators, and the effect of high-dose treatment (H 250 μg / kg) was significantly better than that of low-dose treatment (H 50 μg / kg), close to the level of the normal control group (ie, Sham group). This result further proves that high-dose halofuginone has important therapeutic potential in the recovery of motor function after spinal cord injury.

[0096] Example 6: Immunofluorescence analysis of changes in microglia and astrocytes after spinal cord injury

[0097] The distribution and activation of microglia (green, Iba-1 labeled), astrocytes (red, GFAP labeled) and cell nuclei (blue, DAPI stained) in the sham operation group (Sham), spinal cord injury group (Injury) and halofuginone treatment group (HF) were detected by immunofluorescence labeling (reference Yang B, Liang C, Chen D, et al. Aconductive supramolecular hydrogel creates ideal endogenous niches to promote spinal cord injury repair[J]. Bioactive materials, 2022, 15: 103-119).

[0098] like Figure 7As shown in the figure, in the sham operation group (Sham group), the Iba-1 and GFAP signals were weak and evenly distributed, indicating that microglia and astrocytes were in a resting state; in the spinal cord injury group (Injury group), the Iba-1 and GFAP signals were significantly enhanced, mainly concentrated in the injured area, indicating that microglia and astrocytes were significantly activated; in the fusinone treatment group, compared with the spinal cord injury group, the Iba-1 and GFAP signal intensities were significantly reduced and the distribution was more even, indicating that fusinone can effectively inhibit the excessive activation of microglia and astrocytes and reduce the inflammatory response caused by spinal cord injury.

[0099] Example 7. RNA sequencing to detect gene expression in rats after drug administration

[0100] In this experiment, rats in the spinal cord injury group and rats in the fusinone treatment group (low-dose group and high-dose group) were selected as research subjects. Tissue samples from the spinal cord injury site were taken on the 7th day after spinal cord injury for RNA extraction. After sampling, the tissue samples were immediately frozen in liquid nitrogen and transferred to a -80°C refrigerator for long-term storage. Subsequently, the samples were sent to Hangzhou Lianchuan Biotechnology Co., Ltd. for RNA sequencing analysis. The sequencing data were processed by bioinformatics, including data quality control, alignment to the reference genome, differentially expressed gene analysis, pathway enrichment analysis, etc. The design of this experiment referred to the relevant literature Zhu R, ZhuX, Zhu Y, et al. Immunomodulatory layered double hydroxide nanoparticle senable neurogenesis by targeting transforming growth factor-β receptor 2[J].ACS nano, 2021, 15(2): 2812-2830. The results are as follows Fig. 9 shown.

[0101] The results showed that compared with the spinal cord injury group, multiple neural-related signaling pathways such as neuroactive ligand-receptor interaction (rno04080), GABAergic synapse (rno04727), and synaptic vesicle cycle (rno04721) were significantly enriched in the treatment group, indicating that these pathways may play a key role in regulating neural function under experimental conditions. In addition, calcium signaling pathways (rno04020) and cAMP signaling pathways (rno04024) were also significantly enriched, suggesting the potential importance of these signaling pathways in regulating neural metabolism and functional recovery. The above-mentioned multiple key genes were significantly upregulated, especially the expression of genes related to the CAMP signaling pathway was enhanced, suggesting that fusinone may promote spinal cord injury repair by regulating the CAMP signaling pathway.

[0102] Example 8. Immunofluorescence histochemistry of frozen sections to detect glial fibrillary acidic protein (GFAP) expression

[0103] Since the behavioral experiment has proved that the repair effect of the low-dose treatment group is not as good as that of the high-dose treatment group, the high-dose treatment group was used for further experiments. Six weeks after injury, the spinal cord tissue was stained with GFAP immunofluorescence. In the sham group, less red fluorescence (GFAP) was observed and evenly distributed; a large amount of red fluorescence was observed in the injury area of ​​the Injury group, indicating that a large number of astrocytes proliferated and aggregated; the high-dose treatment group had only less red fluorescence, indicating that there was only mild astrocyte proliferation, and the number of glial scars formed was significantly reduced compared with the Injury group (see Figure 6 ). The above experimental results show that compared with the Injury group, drug treatment can significantly reduce the formation of cavitation and glial scar after spinal cord injury.

[0104] Example 9. Immunofluorescence histochemistry of frozen sections to detect neuronal antigen (NeuN) expression

[0105] Six weeks after injury, NEUN immunohistochemical staining was performed on rat spinal cord tissue (reference: Hsu CC, Wu K LH, Peng JM, et al. Low-energy extracorporeal shockwave therapy improves locomotor functions, tissue regeneration, and modulating the inflammationinduced FGF1 and FGF2 signaling to protect damaged tissue in spinal cord injury of rat model: an experimental animal study [J]. International Journal of Surgery, 2024, 110 (12): 7563-7572). The staining results showed that there were no obvious NEUN (+) neurons in the tissue rupture of the injury group; there were moderate amounts of NEUN (+) neurons in the tissue rupture of the high-dose treatment group. Compared with the injury control group, the number of positive cells in the high-dose treatment group was relatively large (see Figure 8 ). The results showed that the survival rate of neurons in the experimental group was higher than that in the control group.

[0106] The specific embodiments described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. Use of halofuginone in the preparation of a medicament for treating spinal cord injury.

2. Use of halofuginone in the preparation of a drug for promoting the repair of spinal cord injury.

3. Use of halofuginone in the preparation of a drug for promoting recovery of motor ability after spinal cord injury.

4. The use according to claim 3, characterized in that The recovery of athletic ability is manifested as improved athletic ability.

5. The use according to any one of claims 1 to 4, wherein the medicament further comprises a pharmaceutically acceptable carrier or excipient.

6. The use according to any one of claims 1 to 4, wherein the medicament is an oral preparation or an injection.

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