补阳还五汤对脑出血模型大鼠脑组织CXCR4-PI3K自噬信号传导通路及Beclin-1的影响  

Effects of Buyang Huanwu Decoction on CXCR4-PI3K autophagy signal transduction pathway and Beclin-1 in a rat model of cerebral hemorrhage

作　　者：仇志富 吴晓光[1] 祖炳学 时召平 苗惠[4] 李蒙蒙[4] 

机构地区：[1]河北省中医药抗痴呆重点研究室/承德医学院基础医学研究所,河北省承德市067000 [2]抚宁县第二人民医院,河北省秦皇岛市066300 [3]承德市中医院药剂科,河北省承德市067000 [4]承德医学院,河北省承德市067000

出　　处：《中国组织工程研究》2016年第27期3992-3998,共7页Chinese Journal of Tissue Engineering Research

基　　金：河北省卫生厅课题基金(H2015401006);河北省高等学校重点学科病理生理学项目资助(2013)~~

摘　　要：背景:补阳还五汤是治疗脑出血的临床常用药,前期研究已发现其出色的神经保护作用,能够高效的抑制神经细胞凋亡。自噬活动与神经细胞凋亡关系密切,CXCR4-PI3K自噬信号传导通路在少许的临床常用药中已得以验证,然而关于补阳还五汤对其影响却知之甚少;同时对于Beclin-1在补阳还五汤神经保护的研究中尚未见报道。目的:探究补阳还五汤对脑出血大鼠脑组织CXCR4-PI3K自噬信号传导通路与Beclin-1的影响及其相关机制。方法:按照Rosenberg法复制脑出血大鼠模型,以补阳还五汤灌胃给药,采用Western blot法检测Beclin-1蛋白,免疫组化方法检测PI3K、AKT、基质细胞衍生因子1、CXCR-4蛋白表达,TUNEL法检测细胞凋亡情况。结果与结论:(1)补阳还五汤灌胃给药后,能够减轻脑出血大鼠神经细胞凋亡数量,在脑出血发生后几小时上调Beclin-1、PI3K、AKT、基质细胞衍生因子1、CXCR-4等蛋白的表达,发挥脑保护效果;(2)补阳还五汤能够激活CXCR4-PI3K自噬轴信号传导通路,既能够激发细胞自噬,又能够调控细胞自噬状态,实现抑制细胞凋亡的脑保护作用。BACKGROUND： Buyang Huanwu Decoction is commonly used in clinical medicine in treatment of intracerebral hemorrhage. Previous studies have been found that it has excellent neuroprotective effect, can efficiently inhibit the apoptosis of nerve cells. Autophagic activity is closely related to apoptosis of nerve cells. CXCR4-PI3K autophagy signaling pathway has been verified in clinic. However, the effect of Buyang Huanwu Decoction is poorly understood. There is no study on Beclin-1 in the neuroprotective studies of Buyang Huanwu Decoction. OBJECTIVE： To explore the effects of Buyang Huanwu Decoction on CXCR4-PI3K autophagy signaling pathway and Beclin-1 in rats with cerebral hemorrhage and related mechanisms. METHODS： According to Rosenberg method, a rat model of cerebral hemorrhage was replicated and intragastrically administered Buyang Huanwu Decoction. Western blot assay was used to measure Beclin-1 protein. Immunohistochemical method was utilized to detect the expression of PI3K, AKT, stromal cell derived factor 1 and CXCR-4 protein. TUNEL assay was applied to identify apoptosis. RESULTS AND CONCLUSION：（1） After administration, Buyang Huanwu Decoction could reduce the number of neuronal apoptosis in rats with intracerebral hemorrhage, up-regulate the expression of Beclin-1, PI3K, AKT, stromal cell derived factor 1, and CXCR-4 protein, and exert neuroprotective effect.（2） Buyang Huanwu Decoction could activate CXCR4-PI3K autophagy signal transduction pathway, both to stimulate autophagy and to regulate autophagy state, can inhibit apoptosis, and exert cerebral protective effect.

关 键 词：模型 动物 脑出血 细胞凋亡 免疫化学 实验动物 神经损伤与修复动物模型 补阳还五汤 脑出血模型 PI3K/AKT 基质细胞衍生因子1/CXCR4 BECLIN-1 

分 类 号：R318[医药卫生—生物医学工程]