摘要
目的:基于核转录因子-κB/Toll样受体4(NF-κB/TLR4)信号通路探讨葡萄籽提取物对脑缺血再灌注损伤大鼠的保护作用机制。方法:40只SD大鼠随机分为对照组、模型组、葡萄籽提取物低剂量组及葡萄籽提取物高剂量组,每组10只,采用改良线栓法建立脑缺血再灌注损伤大鼠模型。葡萄籽提取物低剂量组、葡萄籽提取物高剂量组于建模成功后分别给予70、140 mg/kg葡萄籽提取物灌胃,对照组和模型组以2 mL/kg生理盐水灌胃,每日1次,连续灌胃7 d。药物干预完成后评估各组大鼠神经缺损情况;苏木精-伊红(HE)染色观察大鼠脑组织病理切片;酶联免疫吸附法(ELISA)检测相关炎性因子水平;蛋白免疫印迹(Western Blot)法检测相关蛋白表达量。结果:对照组大鼠活动正常,精神状态良好;模型组和葡萄籽提取物低剂量组大鼠精神状态不佳、不活跃,经常静止于角落;葡萄籽提取物高剂量组大鼠精神状态有较好改善,有少量活动。HE染色结果显示,对照组大鼠脑细胞正常;模型组大鼠脑细胞部分坏死,正常细胞大量减少,炎性细胞增多,出现脱片现象;葡萄籽提取物低剂量组与葡萄籽提取物高剂量组大鼠脑组织有脱片现象,与模型组比较,脱片现象、炎性细胞浸润明显减少。与对照组比较,模型组、葡萄籽提取物低剂量组、葡萄籽提取物高剂量组大鼠神经缺损评分,白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)水平,TLR4蛋白和NF-κB蛋白相对表达水平,Bax、Caspase-3蛋白表达水平明显升高;Bcl-2蛋白表达水平明显降低(P<0.05)。与模型组比较,葡萄籽提取物低剂量组大鼠神经缺损评分,TLR4蛋白和NF-κB蛋白相对表达水平,Bax、Caspase-3蛋白表达水平明显降低;Bcl-2蛋白表达水平明显升高(P<0.05)。与模型组比较,葡萄籽提取物高剂量组大鼠神经缺损评分,IL-1β、IL-6、TNF-α水平,TLR4蛋白和NF-κB蛋白相对表达水平,Bax、Caspase
Objective:To explore the protective effect of grape seed extract on cerebral ischemia-reperfusion injury of rat model based on nuclear factorκB(NF-κB)/Toll-like receptor 4(NF-κB/TLR4)signaling pathway.Methods:Forty SD rats were randomly divided into control group,model group,grape seed extract low-dose group,and grape seed extract high-dose group,with 10 rats in each group.The rat model of cerebral ischemia-reperfusion injury was established by modified thread thrombus method.After successful modeling,grape seed extract low-dose group and high-dose group were given 70 and 140 mg/kg grape seed extract by intragastric administration,respectively,while control group and model group were given 2 mL/kg normal saline intragastric administration,once a day for 7 days.The nerve defect of each group was evaluated after the drug intervention.Hematoxylin-eosin(HE)staining was used to observe the pathological sections of rat brain.The levels of related inflammatory factors were detected by enzyme-linked immunosorbent assay(ELISA).The expression of related proteins was detected by Western Blot.Results:The rats in control group showed normal activity and better mental state.The mental state of rats in model group and grape seed extract low-dose group was poor,inactive,and often stationary in the corner.The mental state of rats in grape seed extract high-dose group was significantly improved and there was a little activity.HE staining showed that the brain cells of the control group were normal.In the model group,the brain cells were partially necrotic,the normal cells greatly reduced,the inflammatory cells increased.There was delamination in the brain tissue of rats in the grape seed extract low-dose group and the grape seed extract high-dose group,and the delamination and inflammatory cell infiltration decreased significantly compared with the model group.Compared with the control group,the neural deficit scores,the levels of IL-1β,IL-6,TNF-α,the relative expression levels of TLR4 protein and NF-κB protein,and the expre
作者
李丹
徐沙丽
王颖
张俊霞
LI Dan;XU Shali;WANG Ying;ZHANG Junxia(Liyuan Hospital of Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430077,Hubei,China)
出处
《中西医结合心脑血管病杂志》
2023年第19期3527-3531,共5页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
武汉市卫生和计划生育委员会资助项目(No.WZ18Q07)。
