阿托伐他汀对大鼠脑缺血再灌注损伤后神经细胞焦亡的影响
Effect of atorvastatin on neuronal pyroptosis in rats after cerebral ischemia-reperfusion injury
曹瑜 1邢丹1
作者信息
- 1. 215699 江苏,张家港市中医医院药学部
- 折叠
摘要
目的 探讨阿托伐他汀(AVT)对大鼠脑缺血再灌注(CIR)损伤后神经细胞焦亡的影响及机制.方法 选取成年雄性SD大鼠60只,随机分为假手术组(Sham组)、模型组(CIR组)、阿托伐他汀组(AVT组)以及miR-21抑制剂组,每组15只.线栓法制备CIR损伤模型.AVT组大鼠缺血后2、14 h给予AVT灌胃[10 mg/(kg·d)],Sham组大鼠给予等量生理盐水灌胃,miR-21抑制剂组大鼠先脑室注射病毒液(1010 pfu/只)预处理3d后建立CIR模型并在缺血后2、14 h给予AVT灌胃.CIR后1周,采用Lon-ga法进行大鼠神经功能障碍评分,干湿重法检测大鼠脑组织含水量,HE染色观察大鼠海马神经元形态学变化,qRT-PCR检测大鼠海马组织miR-21表达,免疫印迹法检测海马组织细胞焦亡相关蛋白(Caspase-1、GSDMD、IL-1β和IL-18)的表达.结果 与CIR组相比,AVT组大鼠神经功能评分明显改善(P<0.01),脑组织含水量明显降低(P<0.01),海马组织miR-21表达明显升高(P<0.01)、焦亡相关蛋白cleaved-caspase-1、GSDMD-N、IL-1β和IL-18表达水平明显降低(P<0.01).与AVT组相比,miR-21抑制剂组大鼠上述指标显著逆转(P<0.05).结论 AVT能够改善CIR大鼠神经功能损伤,机制可能与上调miR-21表达、抑制神经细胞焦亡相关.
Abstract
Objective To investigate the effect of atorvastatin(AVT)on neuronal pyroptosis in rats after cerebral ischemia-reperfusion(CIR)injury and the underlying mechanisms.Methods Sixty adult male Sprague-Dawley rats were randomly divided into sham group,CIR group,atorvastatin group(AVT group)and miR-21 inhibitor group,with 15 rats in each group.The CIR model was established by thread embolism method.The rats in the AVT group were given AVT[10 mg/(kg·d)]by gavage at 2 and 14 h after ischemia,the rats in the sham group were given the same amount of saline by gavage,and the rats in the miR-21 inhibitor group received intracerebral injection of virus solution(1010 pfu/rat)for 3 days before ischemia and then given AVT by gavage at 2 and 14 h after ischemia.One week after CIR,the neurological dysfunction score was evaluated by Longa method,the water content of brain tissues was measured by dry-wet weight method,the morphological changes of hippocampal tissues were observed by HE staining,the expressions of miR-21 and pyroptosis-related proteins(Caspase-1,GSDMD,IL-1β and IL-18)in hippocampal tissues were detected by qRT-PCR and Western blotting,respectively.Results Compared with the CIR group,the neurological function score was significantly improved(P<0.01),the water content of brain tissues was significantly decreased(P<0.01),the expression level of miR-21 was significantly increased(P<0.01),and the expression levels of pyroptosis-related proteins were significantly decreased in the AVT group(P<0.01).Compared with the AVT group,the above effects were significantly reversed in the miR-21 inhibitor group(P<0.05).Conclusions AVT can improve the neurological function of CIR rats,and the mechanism may be related to up-regulating the expression of miR-21 and inhibiting neuronal pyroptosis.
关键词
脑缺血再灌注损伤/细胞焦亡/阿托伐他汀/miR-21Key words
Cerebral ischemia-reperfusion injury/Atorvastatin/Pyroptosis/miR-21引用本文复制引用
基金项目
江苏省干部保健科研课题(2020)(BJ20043)
出版年
2024
NETL
NSTL
万方数据