基于SIRT1/PGC-1α信号通路探讨抑眩宁颗粒干预缺血性眩晕的作用机制  

Mechanism of Yixuanning Granules on Ischemic Vertigo Based on SIRT1/PGC-1αSignaling Pathway

作　　者：王福荣 李明坤[1] 刘志广[1] 马金波[2] WANG Furong;LI Mingkun;LIU Zhiguang;MA Jinbo(Zhaogezhuang Hospital Kailuan General Hospital,Tangshan 063000,Hebei,China)

机构地区：[1]开滦总医院赵各庄医院,河北唐山063000 [2]开滦总医院,河北唐山063000

出　　处：《中西医结合心脑血管病杂志》2024年第10期1787-1792,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：河北省中医药类科研计划项目(No.2021386)。

摘　　要：目的:探讨抑眩宁颗粒对沉默信息调节因子1(SIRT1)/过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)信号通路的调控作用及对缺血性眩晕大鼠眩晕症状的改善作用。方法:对清洁级SD大鼠进行电刺激逃避反射训练3 d后建立缺血性眩晕模型。将大鼠分为模型组、抑眩宁颗粒组(6 g/kg)、SIRT1抑制剂(EX527)组(5 mg/kg)、抑眩宁颗粒+EX527组(抑眩宁颗粒6 g/kg+EX5275 mg/kg),各组给予相应药物干预7 d;另取16只清洁级SD大鼠作为假手术组(进行造模前训练,仅穿线不结扎)。采用跳台逃避实验测定跳台逃避潜伏期;多普勒激光血流仪测量大鼠前庭神经核组织血流量,计算血流量下降率;苏木精-伊红染色观察大鼠脑组织病理特征;酶联免疫吸附法检测大鼠脑组织丙二醛(MDA)、超氧化物歧化酶(SOD)活性、一氧化氮(NO)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)含量;蛋白免疫印迹法检测大鼠脑组织SIRT1、PGC-1α、B淋巴细胞瘤-2相关X蛋白(Bax)、B淋巴细胞瘤-2(Bcl-2)蛋白表达水平。结果:与假手术组比较,模型组大鼠脑组织神经细胞变形、固缩和凋亡,跳台逃避潜伏期、给药后血流量下降率、脑组织MDA、NO、IL-1β、TNF-α含量、Bax蛋白表达水平升高(P<0.05),SOD活性、SIRT1、PGC-1α和Bcl-2蛋白表达水平降低(P<0.05)。与模型组比较,抑眩宁颗粒组大鼠脑组织凋亡变异的细胞数量减少,胶质周围的正常细胞数量增多,跳台逃避潜伏期、给药后血流量下降率、脑组织MDA、NO、IL-1β、TNF-α含量及Bax蛋白表达水平降低(P<0.05),SOD活性、SIRT1、PGC-1α和Bcl-2蛋白表达水平升高(P<0.05);EX527组大鼠脑组织神经细胞严重变形,固缩和凋亡现象明显,跳台逃避潜伏期、给药后血流量下降率、脑组织MDA、NO、IL-1β、TNF-α含量及Bax蛋白表达水平升高(P<0.05),SOD活性、SIRT1、PGC-1α和Bcl-2蛋白表达水平降低(P<0.05)。EX527可逆转抑眩宁颗粒对Objective:To investigate the regulatory effect of Yixuanning granules on silencing information regulatory factor 1(SIRT1)/peroxisome proliferator-activated receptorγ-coactivator 1α(PGC-1α)signaling pathway and its improvement effect on vertigo symptoms of ischemic vertigo in rats.Methods:After 3 days of escape reflex training of electrical stimulation,rat model of ischemic vertigo was established,a nd the rats were divided into model group,Yixuanning granules group(6 g/kg),SIRT1 inhibitor(EX527)group(5 mg/kg),Yixuanning granules+EX527 group(Yixuanning granules 6 g/kg+EX5275 mg/kg).Each group was given drug for 7 days.Another 16 rats were selected as sham group(pre-modeling training,only threading without ligature).The stage escape latency of rats was measured by the stage escape experiment.The blood flow in vestibular nucleus of rats was measured by Doppler laser blood flow analyzer,and the decreasing rate of blood flow was calculated.Hematoxylin-eosin staining was used to observe the pathological characteristics of rat brain.The activities of malondialdehyde(MDA),superoxide dismutase(SOD),nitric oxide(NO),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).The expressions of SIRT1,PGC-1α,B-lymphoblastoma-2-associated X protein(Bax)and B-lymphoblastoma-2(Bcl-2)in rat brain were detected by Western Blot.Results:Compared with sham group,brain nerve cells in the model group were deformable,constricted and apoptotic,stage escape latency blood flow rate decreased after administration,the activity of MDA,NO,IL-1β,TNF-αcontent and Bax protein expressions in cerebral tissue increased(P<0.05).SOD activity,SIRT1,PGC-1αand Bcl-2 protein expressions decreased(P<0.05).Compared with model group,the number of apoptotic cells in brain tissue of Yixuanning granules group decreased,the number of normal cells around glia increased significantly,the latency of stage escape,the decrease rate of blood flow after administration,the activity of MDA,NO,IL-1β,TNF-αc

关 键 词：缺血性眩晕 抑眩宁颗粒 沉默信息调节因子1/过氧化物酶体增殖物激活受体γ辅激活因子1α SIRT1/PGC-1α 大鼠 实验研究 

分 类 号：R285.5[医药卫生—中药学]