补肾止颤方对帕金森病大鼠Caspase-4/11表达的影响  

Effect of Bushen Zhichan Decoction(补肾止颤方)on Caspase-4/11 Expression in Rats with Parkinson's Disease

作　　者：胡玉英[1] 徐水婷 宋曦[1] 罗荣卿 钟洁[1] 张志伟[1] 王晋平[1] 胡跃强[1] HU Yuying;XU Shuiting;SONG Xi;LUO Rongqing;ZHONG Jie;ZHANG Zhiwei;WANG Jinping;HU Yueqiang(The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,Guangxi,China;Guangxi University of Chinese Medicine,Nanning 530001,Guangxi,China)

机构地区：[1]广西中医药大学第一附属医院,广西南宁530023 [2]广西中医药大学,广西南宁530001

出　　处：《辽宁中医杂志》2023年第7期234-237,I0006,共5页Liaoning Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(8196150085);广西高等学校高水平创新团队及卓越学者计划(桂教人才[2020]6号);广西中医药大学“岐黄工程”高层次人才团队培育项目(2018003);广西中医药大学第一附属医院学术团队建设项目(院字[2018]146号);广西中医脑病临床研究中心项目(桂科AD20238028)。

摘　　要：目的探讨补肾止颤方对帕金森病(Parkinson′s disease,PD)大鼠Caspase-4/11表达的影响。方法采用蛋白酶抑制因子注射法建立慢性PD大鼠模型,将造模成功的大鼠分为模型组、多巴丝肼组(2 g·kg^(-1)·d^(-1)),补肾止颤方低、中、高剂量组(15、30、60 g·kg^(-1)·d^(-1)),假手术组采用等量的70%乙醇溶液注射。假手术组、模型组给予10 mL·kg^(-1)·d^(-1)生理盐水;其余各组给予相应药物;连续灌胃3周。观察大鼠的一般情况,于灌药前1周及灌药后第3周进行悬挂实验并评分。采用HE染色、透射电镜观察中脑黑质区神经元病理改变,qPCR技术检测中脑黑质区α-syn、TH、IL-1β、GSDMD、Caspase-4/11的mRNA表达变化。结果补肾止颤方能增加悬挂实验时间及评分,减轻神经元病理损伤,明显抑制α-syn、IL-1β、GSDMD、Caspase-4/11表达,增加TH表达。结论补肾止颤方可有效改善PD模型大鼠的行为障碍、减轻神经元病理损伤,可能通过下调Caspase-4/11,抑制GSDMD蛋白的表达,减少α-syn、IL-1β分泌,从而减轻细胞焦亡,达到神经元保护作用。Objective To explore the effect of Bushen Zhichan Decoction(补肾止颤方)on cysteinyl aspartate specific proteinase-4/11(Caspase-4/11)in rats with Parkinson's disease(PD).Methods Chronic PD rat models were established by injecting the protease inhibitor,while the sham operation group was injected with 70% ethanol solution of the same amount.The successfully modeled rats were randomly divided into the model group,Levodopa and Benserazide group(2 g·kg^(-1)·d^(-1)),and Bushen Zhichan Decoction low,medium and high dose groups(15,30,60 g·kg^(-1)·d^(-1)).At the same time,the sham operation group and model group were given the normal saline with the dose of 10 mL·kg^(-1)·d^(-1),all with a course of 3 weeks.The general conditions of rats were observed,and the rats in each group were subjected to suspension test and scored at 1 week before and 3 weeks after administration.The pathological changes of neurons in the substantia nigra were observed by HE staining and transmission electron microscopy,and the mRNA expressions of α-syn,TH,IL-1β,GSDMD and Caspase-4/11 were detected by qPCR.Results Compared with those of the model group,the suspension test time and score of Bushen Zhichan Decoction groups increased,the pathological damage of neurons was alleviated,the expressions of α-syn,IL-1β,GSDMD and Caspase-4/11 in the substantia nigra region of midbrain were down-regulated(P<0.05).Meanwhile,the expression of TH was up-regulated significantly(P<0.05).Conclusion Bushen Zhichan Decoction can improve the behavioral disorders effectively,relieve the pathological damage of neurons and alleviate the pyroptosis probably by reducing the expressions of Caspase-4/11,GSDMD,α-syn and IL-1β,and thus achieving the aim of neuronal protection.

关 键 词：补肾止颤方 帕金森病 半胱氨酸天冬氨酸蛋白酶-4/11 细胞焦亡 非经典通路 

分 类 号：R285.5[医药卫生—中药学]