金丝桃苷调节RhoA/ROCK信号通路对创伤性脑损伤大鼠的影响  

Effectss of hyperoside on traumatic brain injury rats by regulating RhoA/ROCK signaling pathway

作　　者：徐渭 陈峰 叶志军[1] XU Wei;CHEN Feng;YE Zhijun(Department of Neurosurgery,Jinhua Municipal Central Hospital,Jinhua 321000,Zhejiang,China)

机构地区：[1]金华市中心医院神经外科,浙江金华321000

出　　处：《中国临床药理学与治疗学》2023年第4期383-390,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：金华市重大科学技术研究计划项目(2021-3-096)。

摘　　要：目的:探讨金丝桃苷调节Ras同源基因家族成员A(RhoA)/Rho相关的卷曲螺旋激酶(ROCK)信号通路对创伤性脑损伤(TBI)大鼠的影响。方法:采用改良Feeney自由落体打击法构建TBI大鼠模型,随机分为模型组、金丝桃苷低剂量(60 mg/kg)组、金丝桃苷高剂量(120 mg/kg)组、金丝桃苷高剂量(120 mg/kg)+空载组、金丝桃苷高剂量(120mg/kg)+RhoA过表达组,每组均10只,另取10只健康大鼠设定为假手术组,采用金丝桃苷和质粒分组处理后,以改良神经功能缺损评分(m NSS)和避暗实验检测大鼠神经损伤;以伊文思蓝(EB)定量法检测大鼠血脑屏障通透性;以透射电镜观察大鼠血脑屏障超微结构损伤;以试剂盒检测大鼠血清及脑组织炎症因子肿瘤坏死因子α(TNF-α)、白细胞介素-8(IL-8)与氧化应激因子超氧化物歧化酶(SOD)、丙二醛(MDA)水平;以蛋白免疫印迹检测大鼠脑组织RhoA/ROCK通路相关蛋白表达。结果:与假手术组比较,模型组大鼠血脑屏障结构发生损伤,步入潜伏期、SOD水平显著降低(P<0.05),mNSS评分、犯错次数、脑组织EB含量、血清及脑组织TNF-α、IL-8、MDA水平、脑组织RhoA、ROCK1、ROCK2蛋白表达显著升高(P<0.05)。与模型组比较,金丝桃苷低剂量组、金丝桃苷高剂量组大鼠血脑屏障结构损伤均减轻,步入潜伏期、SOD水平均升高(P<0.05),mNSS评分、犯错次数、脑组织EB含量、血清及脑组织TNF-α、IL-8、MDA水平、脑组织RhoA、ROCK1、ROCK2蛋白表达均降低(P<0.05);金丝桃苷高剂量组作用更强。过表达RhoA可逆转高剂量金丝桃苷对TBI大鼠各指标的影响;金丝桃苷高剂量+空载组大鼠各指标变化相近(P>0.05)。结论:金丝桃苷可通过下调RhoA/ROCK信号通路而抑制TBI大鼠神经炎症及氧化应激,从而减轻其血脑屏障损伤,修复其神经功能。AIM:To investigate the effects of hyperoside on traumatic brain injury(TBI)rats by regulating the Ras homolog gene family,member A(RhoA)/Rho-associated coiled coil-forming kinase(ROCK)signal pathway.METHODS:The TBI rat model was established by modified Feeney free fall hit method,and was randomly divided into model group,low-dose hyperoside(60 mg/kg)group,high-dose hyperoside(120 mg/kg)group,highdose hyperoside(120 mg/kg)+no load group,and high-dose hyperoside(120 mg/kg)+RhoA overexpression group,with 10 rats in each group,another 10 healthy rats were set as sham operation group,after hyperoside and plasmid were grouped,the nerve injury was detected by modified neurological deficit score(mNSS)and dark avoidance test;Evans blue(EB)quantitative method was used to detect the permeability of blood brain barrier in rats;ultrastructural damage of blood-brain barrier was observed by transmission electron microscopy;the levels of tumor necrosis factor-α(TNF-α),interleukin-8(IL-8),superoxide dismutase(SOD)and malondialdehyde(MDA)in serum and brain tissue of rats were measured with the kit;and the expression of RhoA/ROCK pathway related proteins in rat brain was detected by Western blot.RESULTS:Compared with the sham operation group,the blood brain barrier structure of the model group rats was damaged,the step-through latency and SOD level decreased obviously(P<0.05),the mNSS score,the number of mistakes,the content of EB in brain tissue,the levels of TNF-α,IL-8,MDA in serum and brain tissue,and the expression of RhoA,ROCK1,ROCK2 proteins in brain tissue increased obviously(P<0.05).Compared with the model group,the damage of blood brain barrier structure of rats in the low-dose hyperoside group and the high-dose hyperoside group was alleviated,the step-through latency and SOD level increased(P<0.05),the mNSS score,the number of mistakes,the content of EB in brain tissue,the levels of TNF-α,IL-8,MDA in serum and brain tissue,and the expression of RhoA,ROCK1,ROCK2 proteins in brain tissue all decreased(P<0.05);high-dose

关 键 词：金丝桃苷 RhoA/ROCK 创伤性脑损伤 血脑屏障 

分 类 号：R965.2[医药卫生—药理学]