VX-765通过抑制细胞焦亡改善脑卒中后中枢痛*

doi:10.3870/j.issn.1672-0741.26.01.007

摘要/Abstract

摘要： 目的探讨细胞焦亡是否参与脑卒中后中枢痛(central post-stroke pain,CPSP)的病理生理过程,以及VX-765能否通过抑制NLRP3/GSDMD/IL-1β通路改善CPSP所致的中枢敏化。方法采用远端大脑中动脉电凝法(dMCAO)建立CPSP小鼠模型。将40只8周龄C57BL/6J小鼠随机分为4组:CPSP+VX-765组、CPSP+Vehicle组、Sham+VX-765组、Sham+Vehicle组。通过Western blot检测脑组织中NLRP3、GSDMD-N、Caspase-1及IL-1β的蛋白表达水平;尼氏染色观察神经元存活与死亡情况;使用von Frey纤维丝测定双侧后爪机械缩足阈值(PWMT);采用Hargreaves法检测双侧后爪热缩足潜伏期(PWTL)。结果造模后第14天,与Sham+Vehicle组相比,CPSP+Vehicle组脑内NLRP3、GSDMD-N、Caspase-1及IL-1β表达显著升高,梗死灶周围尼氏小体溶解,存活神经元减少,双侧后爪PWMT与PWTL均显著降低。VX-765干预后,CPSP+VX-765组焦亡相关蛋白表达下降,梗死灶周边神经元存活数量增加,双侧后爪PWMT与PWTL均较CPSP+Vehicle组提高。结论 VX-765可能通过抑制NLRP3/GSDMD/IL-1β通路,减少细胞焦亡,发挥神经保护作用,改善CPSP诱导的中枢敏化。

关键词: 脑卒中后中枢痛, 痛觉过敏, 炎症, 细胞焦亡, 半胱天冬酶抑制剂

Abstract: Objective To investigate whether pyroptosis occurs in central post-stroke pain(CPSP)and whether modulation of the NLRP3/GSDMD/IL-1β pathway can alleviate central sensitization. Methods A CPSP model was established by distal middle cerebral artery occlusion via electrocoagulation(dMCAO).C57BL/6J mice were randomly assigned to four groups:Sham+Vehicle,Sham+VX-765,CPSP+Vehicle,and CPSP+VX-765.Protein levels of NLRP3,GSDMD-N,Caspase-1,and IL-1β were measured by Western blotting.Neuronal survival was assessed via Nissl staining.Mechanical and thermal withdrawal threshold of bilateral hind paws were evaluated using von Frey filaments and the Hargreaves test,respectively. Results On day 14 post-modeling,compared with the Sham+Vehicle group,the CPSP+Vehicle group exhibited significantly increased expression of NLRP3,GSDMD-N,Caspase-1 and IL-1β.Neurons around the infarct area showed dissolution and loss of Nissl bodies,along with reduced cell survival.Both mechanical and thermal withdrawal thresholds were significantly decreased.Following VX-765 intervention,the CPSP+VX-765 group displayed decreased expression level of pyroptosis-related proteins,increased neuronal survival around the infarct,and improved withdrawal thresholds. Conclusion VX-765 exerts neuroprotective effects and alleviates central sensitization in CPSP by inhibiting the NLRP3/GSDMD/IL-1β pathway.

Key words: central post-stroke pain, hyperalgesia, inflammation, pyroptosis, Caspase inhibitor

中图分类号:

R743.3

刘倩文, 叶樱泽, 佘科鹏, 李美红, 罗放, 张玥. VX-765通过抑制细胞焦亡改善脑卒中后中枢痛^*[J]. 华中科技大学学报（医学版）, 2026, 55(2): 149-154.

Liu Qianwen, Ye Yingze, She Kepeng et al. VX-765 Attenuates Central Post-Stroke Pain by Inhibiting Pyroptosis[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(2): 149-154.

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VX-765通过抑制细胞焦亡改善脑卒中后中枢痛^*

VX-765 Attenuates Central Post-Stroke Pain by Inhibiting Pyroptosis

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