基于NLRP3/Caspase-1信号通路探讨清脑通络汤对脑小血管病伴认知障碍大鼠的影响  

Effects of decoction for clearing brain and unblocking collaterals on the rat model of cerebral small vessel diseasewith cognitive impairment through the NLRP3/Caspase-1 signaling pathway

作　　者：王海霞 杨一帆 胡楠 谢欣纯 彭涛 徐培丽 闫咏梅 王涛[1,4] WANG Haixia;YANG Yifan;HU Nan;XIE Xinchun;PENG Tao;XU Peili;YAN Yongmei;WANG Tao(Shaanxi University of Chinese Medicine,Xianyang 712046,Shaanxi,China;Xianyang Hospital of Yan’an University,Xianyang 712099,Shaanxi,China;Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,Shaanxi,China;Shaanxi Provincial People’s Hospital,Xi’an 710068,Shaanxi,China)

机构地区：[1]陕西中医药大学,陕西咸阳712046 [2]延安大学咸阳医院,陕西咸阳712099 [3]陕西中医药大学附属医院,陕西咸阳712000 [4]陕西省人民医院,陕西西安710068

出　　处：《现代中西医结合杂志》2024年第17期2337-2341,2352,共6页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：国家自然科学基金面上项目(81973843);国家岐黄学者支持项目(国中医药人教函[2022]6号);陕西省中医脑病学重点实验室项目(KF2214);研究生创新实践能力提升项目(CXSJ202320)。

摘　　要：目的观察清脑通络汤通过核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)/半胱氨酸天冬氨酸酶-1(Caspase-1)信号通路对脑小血管病伴认知障碍大鼠的影响。方法将18只SD大鼠随机分为假手术组、模型组和清脑通络汤组,每组6只。采用内皮素-1立体定位海马CA1区注射法建立脑小血管病伴认知障碍模型。术后3 d清脑通络汤组给予清脑通络汤2.08 mL/100 g灌胃,假手术组及模型组给予等体积生理盐水灌胃,均1次/d,连续灌胃28 d。Morris水迷宫测试大鼠的空间学习和记忆能力,透射电子显微镜观察海马神经细胞凋亡情况,HE染色观察海马神经细胞形态,Western blot法检测海马组织中NLRP3和Caspase-1蛋白表达情况。结果与假手术组比较,模型组大鼠第2~5天的逃避潜伏期均明显延长(P均<0.05),穿越平台次数明显减少(P<0.05),海马组织中NLRP3、Caspase-1蛋白相对表达量均明显升高(P均<0.05);透射电子显微镜下见线粒体肿胀,线粒体嵴减少或消失,线粒体基质部分溶解,高尔基体轻度肿胀;HE染色见海马神经细胞数量减少,可见空泡样改变。与模型组比较,清脑通络汤组大鼠第2~5天的逃避潜伏期均明显缩短(P均<0.05),穿越平台次数明显增加(P<0.05),海马组织中NLRP3、Caspase-1蛋白相对表达量均明显降低(P均<0.05);线粒体受损明显减轻,海马神经细胞坏死明显减少。结论清脑通络汤通过抑制NLRP3/Caspase-1信号通路激活,减轻细胞焦亡,从而改善脑小血管病伴认知障碍大鼠的认知障碍。Objective It is to observe the effects of decoction for clearing brain and unblocking collaterals on rat model of cerebral small vessel disease with cognitive impairment through the NLRP3/Caspase-1 signaling pathway.Methods Eighteen SD rats were randomly divided into sham operation group,model group and group of decoction for clearing brain and unblocking collaterals,with 6 rats in each group.The models of cerebral small vessel disease with cognitive impairment were established by endothelin-1 stereotactic hippocampal CA1 area injection in the rats.In 3 days after operation,the group of decoction for clearing brain and unblocking collaterals was given decoction for clearing brain and unblocking collaterals 2.08 mL/100 g by gavage,and the sham operation group and model group were given equal volume of normal saline by gavage,all once daily,continuously treated for 28 days.The spatial learning and memory abilities of the rats were tested bt Morris water maze,the apoptosis of hippocampal neurons was observed by transmission electron microscopy,the morphology of hippocampal neurons was observed by HE staining,and the protein expressions of NLRP3 and Caspase-1 in hippocampal tissue were detected by Western blot method.Results Compared with the sham operation group,the escape latency of rats in the model group was significantly prolonged from day 2 to 5(both P<0.05),the time of crossing platforms was significantly reduced(P<0.05),and the relative protein expressions of NLRP3 and Caspase-1 in hippocampal tissues were significantly increased(both P<0.05);transmission electron microscopy showed that mitochondria was swollen,mitochondrial cristae was reduced or disappeared,mitochondrial matrix was partially dissolved,and the Golgi apparatus was mildly swollen.Compared with the model group,the escape latency from day 2 to 5 of the rats in the group of decoction for clearing brain and unblocking collaterals was significantly shortened(P<0.05),and the time of crossing platforms was significantly increased(P<0.05),the relative

关 键 词：清脑通络汤 脑小血管病伴认知障碍 炎症反应 细胞焦亡 

分 类 号：R-332[医药卫生]