摘要
目的:探讨扁蒴藤素(PT)通过调节环磷酸鸟苷-腺苷酸合成酶/干扰素基因刺激因子(cGAS/STING)信号通路对缺血性脑卒中大鼠认知功能和神经炎症的影响。方法:采用线栓法建立MCAO模型,将大鼠随机分为Control组,MCAO组,扁蒴藤素低、中、高剂量组(PT-L组、PT-M组、PT-H组),PT-H+cGAS/STING通路激活剂组(PT-H+DMXAA组),采用Zea-Longa评分对大鼠进行神经性行为评分;Morris水迷宫评估大鼠的认知能力;2,3,5-氯化三苯基四氮唑(TTC)染色法观察并计算大鼠脑梗死面积;HE染色法观察大鼠脑组织病理变化情况;酶联免疫吸附试验(ELISA)检测中大鼠血清中白介素(IL-6)和白介素(IL-1β)水平;Western blot法检测大鼠脑组织中小胶质细胞M1型标记物(iNOS)、小胶质细胞M2型标记物(Arg-1)、cGAS、STING蛋白表达水平。结果:与Control组比较,MCAO组大鼠神经功能缺损评分、逃避潜伏期、脑梗死面积、IL-6、IL-1β水平及iNOS、cGAS、STING表达显著升高,Arg-1表达显著降低(P<0.05);与MCAO组比较,PT各组大鼠神经功能缺损评分、逃避潜伏期、脑梗死面积、IL-6、IL-1β水平及iNOS、cGAS、STING蛋白表达水平显著降低,Arg-1表达显著升高(P<0.05),且呈剂量依赖性;与PT-H组比较,PT-H+DMXAA组大鼠神经功能缺损评分、逃避潜伏期、脑梗死面积、IL-6、IL-1β水平及iNOS、cGAS、STING表达显著升高,Arg-1表达显著降低(P<0.05)。结论:扁蒴藤素可以缓解缺血性脑卒中大鼠认知功能障碍和神经炎症损伤,其作用机制可能与抑制cGAS/STING信号通路相关。
Objective:To investigate the effects of pristimerin(PT)on cognitive function and neuroinflammation in ischemic stroke rats by modulating the cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS/STING)signaling pathway.Methods:The middle cerebral artery occlusion(MCAO)model was established by using the filament occlusion method.Rats were randomly assigned to the control group,MCAO group,low,medium,and high-dose PT groups(PT-L group,PT-M group,PT-H group),and PT-H+DMXAA group(PT-H+DMXAA group).Zea-Longa score was employed to evaluate the neurological behavior of rats.The Morris water maze was used to assess the cognitive ability of the rats.Cerebral infarction area was calculated by using the 2,3,5-chlorophenyltetrazolium(TTC)staining method.Pathological changes in rat brain tissue were observed via hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was performed to measure serum levels of interleukin-6(IL-6)and interleukin-1β(IL-1β).Western blot analysis was utilized to determine the expression levels of M1 marker(iNOS),M2 marker(Arg-1),cGAS,and STING proteins in microglia of rat brain tissue.Results:When compared to the control group,rats in the MCAO group exhibited significantly increased neurological deficit scores,prolonged escape latencies,larger cerebral infarction areas,elevated IL-6 and IL-1βlevels,and higher expression of iNOS,cGAS,and STING.The expression of Arg-1 decreased significantly(P<0.05).In comparison to the MCAO group,rats in the PT groups showed significantly reduced neurological deficit scores,escape latencies,cerebral infarction areas,IL-6 and IL-1βlevels,as well as the expression of iNOS,cGAS,and STING.The expression of Arg-1 increased significantly(P<0.05)in a dose-dependent manner.In comparison to the PT-H group,rats in the PT-H+DMXAA group had significantly higher neurological deficit scores,prolonged escape latencies,larger cerebral infarction areas,increased IL-6 and IL-1βlevels,and higher expression of iNOS,cGAS,and STING.The expression of Arg-1 decreased significantly(P<0.05).Conclusion:Pristimerin can mitigate cognitive impairment and neuroinflammatory damage in ischemic stroke rats.Its mechanism of action may be associated with the inhibition of the cGAS/STING signaling pathway.
作者
林晓燕
方丽鑫
黄丽霞
杨杰书
LIN Xiaoyan;FANG Lixin;HUANG Lixia(Qingdao Central Hospital Affiliated to Qingdao University,Shandong Qingdao 266013,China)
出处
《河北医学》
CAS
2023年第11期1761-1767,共7页
Hebei Medicine
基金
山东省青岛市医药卫生科研指导项目立项书,(编号:2022-WJZD053)。
