红景天苷对脑缺血再灌注大鼠的作用及机制

The effect and mechanism of salidroside on cerebral ischemia-reperfusion in rats

目的研究红景天苷对脑缺血再灌注大鼠的作用及机制。方法SD大鼠随机分为假手术组、脑缺血组、红景天苷组(50 mg·kg^(-1))与红景天苷+PD98059组(50 mg·kg^(-1)+1 mg·kg^(-1)),每组15只。采用中动脉栓塞法造模,利用TTC染色检测大鼠脑梗死区域,TUNEL染色检测大鼠脑中神经元凋亡,Western blot检测各蛋白表达。结果与假手术组相比,脑缺血组大鼠神经功能评分减少,出现局部梗死区域,TUNEL染色阳性细胞数增加,SOD、GSH-PX等抗氧化酶含量降低,MDA含量升高(P<0.05)。与脑缺血组相比,红景天苷介导p-ERK1/2、p-Nrf2与HO-1表达增加(P<0.05),逆转Bax与cleaved-caspasd-3表达(P<0.05),升高SOD与GSH-PX含量,降低MDA含量,同时减少脑缺血大鼠局部梗死区域,提高大鼠的神经功能评分。红景天苷+PD98059组中PD98059通过抑制ERK1/2磷酸化逆转红景天苷对脑缺血大鼠的治疗效果,降低SOD与GSH-PX含量,升高MDA含量,增加大鼠的脑梗死体积,最终减少大鼠的神经功能评分。结论红景天苷基于ERK1/2激活的Nrf2/HO^(-1)信号通路改善脑缺血大鼠神经元凋亡,减少氧化应激反应,缓解大鼠神经功能损伤。

Objective Objective To explore the effect and mechanism of salidroside on middle cerebral artery occlusion(MCAO)/reperfusion rats.Methods SD rats were randomly divided into sham group,MCAO group,salidroside group(50 mg·kg^(-1))and salidroside+PD98059 group(50 mg·kg^(-1) +1 mg·kg^(-1)),15 animals per group.The middle artery occlusion operations were applied for the model,TTC staining experiments were applied for the cerebral infarction area detection,TUNEL staining experiments were used to detect the neuronal apoptosis in brain,and Western blot experiments were used for the protein expression detection.Results Compared with the sham group,the neurological scores of the rats in MCAO group decreased,local infarcts appeared in the brain and the number of TUNEL staining positive cells increased.In addition,the contents of antioxidant enzymes like SOD,GSH-PX decreased,and the contents of MDA increased(P<0.05).Compared with MCAO group,administration of salidroside mediated the increase of p-ERK1/2,p-Nrf2 and HO-1 expression(P<0.05),and reversed the expression of Bax and cleaved-caspasd-3(P<0.05),increased the contents of SOD and GSH-PX,decreased the content of MDA.At the same time salidroside reduced the local infarct area in rats with cerebral ischemia,and improved the neurological scores of the rats.However,the results in salidroside+PD98059 group showed PD98059 reversed the therapeutic effect of salidroside on cerebral ischemia in rats through inhibited ERK1/2 phosphorylation,which reduced the contents of SOD,GSH-PX and increased the content of MDA,increased the volume of cerebral infarction,and finally decreased the neurological function score of rats.Conclusion Salidroside can improve neuronal apoptosis in cerebral ischemic rats,reduce oxidative stress response,and relieve neurological damage through the Nrf2/HO^(-1) signaling pathway activated by ERK1/2.