长托宁抑制NLRP3炎症小体调节脑缺血再灌注大鼠小胶质细胞极化改善脑损伤  

Penehyclidine hydrochloride inhibits NLRP3 inflammatory bodies and regulates the polarization of microglia in rats with cerebral ischemia-reperfusion to improve brain injury

作　　者：张晓敏 伦明辉 黄泽清 ZHANG Xiao-min;LUN Ming-hui;HUANG Ze-qing(Department of Anesthesiology,Cancer Hospital of China Medical University Liaoning Cancer Hospital&Institute,Shenyang 110042,China)

机构地区：[1]中国医科大学肿瘤医院辽宁省肿瘤医院麻醉科,辽宁沈阳110042

出　　处：《解剖科学进展》2022年第3期323-326,334,共5页Progress of Anatomical Sciences

基　　金：辽宁省自然科学基金(20180550218)。

摘　　要：目的 探究长托宁对大鼠脑缺血再灌注致脑损伤的保护作用及可能的机制。方法 30只SD大鼠随机分成假手术组、模型组及长托宁组,每组10只。水迷宫实验检测大鼠认知能力变化;HE染色观察脑组织形态学变化;TUNEL方法检测脑组织神经元细胞凋亡;免疫荧光检测脑组织小胶质细胞极化;ELISA方法检测脑组织炎症因子水平;Western blot检测NLRP3炎症小体相关蛋白表达。结果 长托宁治疗增加脑缺血再灌注损伤大鼠认知能力,改善大鼠脑组织形态,降低脑组织神经元细胞凋亡水平、M2型小胶质细胞比例、IL-1β和IL-18水平及NLRP3、caspase-1和ASC蛋白表达水平,增加脑组织M1型小胶质细胞比例。结论 长托宁减轻大鼠脑缺血再灌注脑损伤,其作用机制可能与抑制NLRP3炎症小体有关。Objective To explore the protective effect and possible mechanism of penehyclidine hydrochloride on brain injury induced by cerebral ischemia/reperfusion in rats. Methods Thirty SD rats were randomly divided into sham operation group, model group and penehyclidine hydrochloride group, with 10 rats in each group. Water maze test was used to detect the change of cognitive ability of rats. The morphological changes of brain tissue were observed by HE staining.TUNEL assay was used to detect neuronal apoptosis in brain tissue. Immunofluorescence was used to detect the polarization of microglia in brain tissue. The levels of inflammatory cytokines in brain tissues were detected by ELISA. The expression of NLRP3 inflammasome associated proteins was detected by Western blot. Results Penehyclidine hydrochloride treatment increases the cognitive ability of rats with cerebral ischemia-reperfusion injury, improves the morphology of rat brain tissue,reduces the level of neuronal cell apoptosis, the proportion of M2 type microglia, the level of IL-1β and IL-18 in the brain tissue and NLRP3, caspase-1 and ASC protein expression levels, increase the proportion of M1 type microglia in brain tissue. Conclusion Penehyclidine hydrochloride alleviates brain injury caused by cerebral ischemia/reperfusion in rats,and the mechanism may be related to the inhibition of NLRP3 inflammasome.

关 键 词：长托宁 缺血再灌注 脑损伤 小胶质细胞极化 NLRP3 

分 类 号：R651.1[医药卫生—外科学]