癫痫清颗粒调控Sigma 1受体抑制阿尔茨海默病模型小鼠炎症小体研究

来源:用户上传      作者:杨彩瑜 李荧 齐越 明彩荣 董笑博 贾冬

　　[摘要] 目的 研究d痫清颗粒是否通过调控Sigma 1受体的表达，抑制阿尔茨海默病（AD）模型小鼠炎症小体的活性。 方法 将小鼠随机分为假手术组、模型组、盐酸多奈哌齐组、癫痫清颗粒组、Sigma 1受体拮抗剂（BD1047）组和BD1047+癫痫清颗粒组。除假手术组外，其余各组小鼠的左侧侧脑室内注射淀粉样蛋白（Aβ25-35）制作AD小鼠模型，连续给药21 d，每日1次。第16天至第21天，Morris水迷宫试验检测小鼠的学习记忆能力，第22天，各组小鼠取材，HE染色观察脑组织病理学变化，免疫组化法及免疫印迹法检测核苷酸结合寡聚化结构域样受体蛋白1（NLRP1）、胱冬肽酶-1（caspase-1）的表达，免疫荧光法检测Sigma 1受体的表达。 结果 与模型组相比，癫痫清颗粒组可减少AD模型小鼠的游泳总路程，降低海马中NLRP1的表达，抑制caspase-1活性，增加Sigma 1受体表达。BD1047组与BD1047+癫痫清颗粒组小鼠中的游泳总路程与模型组小鼠相比，差异无统计学意义（P>0.05），NLRP1和caspase-1的蛋白表达水平升高，Sigma 1受体的表达降低。 结论 癫痫清颗粒可通过激活Sigma 1受体减少NLRP1表达，并抑制caspase-1活性，从而提高AD模型小鼠学习记忆功能。
　　[关键词] 癫痫清颗粒;阿尔茨海默病;炎症小体;Sigma1受体
　　[中图分类号] R749.16 [文献标识码] A [文章编号] 1673-9701（2022）02-0029-05
　　Inhibitory effect of Dianxianqing Granule on inflammasome of Alzheimer's disease model mice by regulating Sigma 1 receptor
　　YANG Caiyu1 LI Ying1 QI Yue1， 2 MING Cairong1 DONG Xiaobo1 JIA Dong2
　　1.Graduate School of Liaoning University of Traditional Chinese Medicine， Shenyang 110847， China; 2.The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine， Shenyang 110034， China
　　[Abstract] Objective To study whether Dianxianqing Granule inhibit the activity of inflammasome in Alzheimer's disease （AD） model mice by regulating the expression of Sigma 1 receptor. Methods The mice were randomly divided into sham operation group， model group， donepezil hydrochloride group， Dianxianqing Granule group， Sigma1 receptor antagonist （BD1047） group， BD1047+Dianxianqing Granule group. Excepted for the sham group， the AD mouse model was made by injecting amyloid （Aβ25-35） into the left lateral ventricle of mice in the other groups once daily for 21 consecutive days. From Day 16 to Day 21， the learning and memory ability of the mice was detected by the Morris water maze. On Day 22， the mice in each group were sampled. The histopathological changes were observed by HE staining. The expression of nucleotide-binding oligomerization domain-like receptor protein 1 （NLRP1） and caspase-1 was detected by immunohistochemistry and immunoblotting. The expression of the Sigma 1 receptor was detected by immunofluorescence assay. Results Compared with the model group， the Dianxianqing Granule group could reduce the total swimming distance， decrease the expression of NLRP1， inhibit caspase-1 activity and increase Sigma 1 receptor expression in the hippocampus of AD model mice. There were no statistically significant differences in the total swimming distance among the BD1047 group， the BD1047+Dianxianqing Granule group， and the model group（P>0.05）. The protein expression levels of NLRP1 and caspase-1 in the BD1047 group and the BD1047+Dianxianqing Granule group were increased， and the expression of the Sigma 1 receptor was decreased. Conclusion Dianxianqing Granule can reduce NLRP1 expression and inhibit caspase-1 activity by activating the Sigma 1 receptor， thereby improving learning and memory function in AD model mice.
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