薯蓣皂苷元对缺血性脑卒中大鼠神经运动功能及TLR4-MyD88/TRIF信号通路调节作用研究  

The regulatory effect of diosgenin on neuromotor function and TLR4-MyD88/TRIF signal⁃ing pathway in rats with ischemic stroke

作　　者：黎艳[1] 王世栋 黄文川[1] Li Yan;Wang Shidong;Huang Wenchuan(Department of Integrated Traditional Chinese and Western Medicine,Nanning Second People's Hospital,Nanning 530031,China)

机构地区：[1]广西南宁市第二人民医院中西医结合科,南宁530031

出　　处：《广西医科大学学报》2021年第12期2319-2324,共6页Journal of Guangxi Medical University

摘　　要：目的:研究薯蓣皂苷元对缺血性脑卒中大鼠神经运动功能及TLR4-MyD88/TRIF信号通路的调节作用。方法:将大鼠随机分为假手术组、缺血性脑卒中模型组、薯蓣皂苷元低、中、高剂量组及阳性对照组,每组12只。采用四血管阻断法建立缺血性脑卒中大鼠模型,薯蓣皂苷元各剂量组分别灌胃给予12.5 mg/kg、25 mg/kg及50 mg/kg的薯蓣皂苷元,阳性对照组给予大鼠尼莫地平,1次/d,连续21 d。测定给药前后大鼠神经功能缺损评分,使用Morris水迷宫测定大鼠逃避潜伏期及90 s内穿过平台的次数;酶联免疫吸附(ELISA)法测定脑组织Toll样受体(TLR)-2、白介素(IL)-1β、IL-6及肿瘤坏死因子(TNF)-α水平;苏木精—伊红(HE)染色法测定脑组织病理改变;实时定量聚合酶链式反应(RT-qPCR)及免疫印迹法(Western blotting)测定大鼠脑组织TLR4、MyD88、TRIF mRNA及蛋白水平。结果:与缺血性脑卒中模型组比较,薯蓣皂苷元各剂量组及阳性对照组大鼠神经功能缺损评分、逃避潜伏期、脑组织TLR-2、IL-1β、IL-6及TNF-α水平,脑组织TLR4、MyD88及TRIF mRNA及蛋白水平均明显降低(均P<0.05),90 s内穿越平台次数显著增加(P<0.05),大鼠脑组织病理性变化明显恢复,且各项指标变化与薯蓣皂苷元的剂量表现出依赖性。结论:薯蓣皂苷元能够修复缺血性脑卒中大鼠神经运动功能及神经损伤,抑制脑组织炎症反应,其机制可能与调节TLR4-MyD88/TRIF信号通路有关。Objective:To study the regulatory effects of diosgenin on neuromotor function and TLR4-MyD88/TRIF signaling pathway in rats with ischemic stroke.Methods:Rats were randomly divided into sham-operated group,ischemic stroke model group,diosgenin low-dose,medium-dose and high-dose groups,and positive control group,with 12 rats each group.The model of ischemic stroke was established by 4-vessels occlusion(4-VO)method.The rats in low-,medium-and high-dose of diosgenin groups were intragastric administered 12.5 mg/kg,25 mg/kg and 50 mg/kg diosgenin respectively.The positive control group rats were given nimodipine once a day for 21 days.The scores of neurological deficits in rats before and after administration were measured.Morris water maze was used to measure the latency period of rats and the times of crossing the platform within 90 seconds.Toll-like receptor-2(TLR-2),interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)levels in brain tissue were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was performed to observe the pathological changes of rat brain tissue.The mRNA and protein levels of TLR4,MyD88 and TRIF in rats brain tissues were determined by RT-qPCR and Western blotting.Results:Compared with the ischemic stroke model group,diosgenin showed a dose-dependent reduction in the neurological deficit score,escape latency,the TLR-2,IL-1β,IL-6 and TNF-αlevels,and TLR4,MyD88 and TRIF expressions,and manifested an increase in the times of crossing platforms within 90 seconds(P<0.05).The pathological damages of rat brain tissue were significantly attenuated by the treatment of diosgenin.Conclusion:Diosgenin can repair neuromotor function and nerve damage of ischemic stroke rats,and inhibit the brain inflammatory response.The mechanism may be related to the regulation of TLR4-MyD88/TRIF pathway.

关 键 词：薯蓣皂苷元 缺血性脑卒中 TLR4-MyD88/TRIF信号通路 

分 类 号：R322[医药卫生—人体解剖和组织胚胎学]