隐丹参酮对脑卒中大鼠PI3K/AKT-eNOS信号通路的影响研究

The effect of cryptotanshinone on PI3K/AKT-eNOS signaling pathway in stroke rats

目的 探讨隐丹参酮对脑卒中大鼠的保护作用及对PI3K/AKT-eNOS信号通路的影响。方法 将40只SD大鼠随机分为对照组、脑卒中模型组、低剂量隐丹参酮组(5 mg/kg)、中剂量隐丹参酮组(15 mg/kg)与高剂量隐丹参酮组(45 mg/kg),每组均8只,采用线栓法建立大鼠脑卒中模型。采用酶联免疫吸附法测定大鼠大脑皮质和外周血中SOD、MDA及NO水平,Western blot法检测大鼠脑组织PI3K及AKT的表达,qRT-PCR分析评估Bcl-2,Bax和VEGF的表达水平。结果 与对照组相比,脑卒中模型组PI3K磷酸化、VEGF、eNOS、MDA水平增加(P<0.05);隐丹参酮组PI3K膜易位、AKT磷酸化、VEGF、eNOS、MDA水平减弱(P<0.05);且与剂量呈负相关(P<0.05)。与对照组相比,脑卒中组NO、SOD、Bcl-2、Bax水平显著下降(P<0.05),隐丹参酮组NO、SOD、Bcl-2、Bax水平升高(P<0.05),且与剂量呈正相关(P<0.05)。结论 隐丹参酮对脑卒中大鼠脑组织具有保护作用,其作用机制可能与其抑制PI3K/AKT-eNOS信号通路有关。

Objective To explore the protective effect of cryptotanshinone on stroke rats and its influence on PI3K/AKT-eNOS signaling pathway.Methods Forty SD rats were randomly divided into the control group,the stroke model group,the low-dose cryptotanshinone group(5 mg/kg),the medium-dose cryptotanshinone group(15 mg/kg),and the high-dose cryptotanshinone group(45 mg/kg),with eight rats in each group.The rat stroke model was established by the suture method.Enzyme-linked immunosorbent assay was used to determine the levels of SOD,MDA,and NO in rat cerebral cortex and peripheral blood.Western blot method was used to detect the expression of PI3K and AKT in rat brain tissue.The expression of Bcl-2,Bax,and VEGF was evaluated by qRT-PCR analysis.Results Compared with the control group,the levels of PI3K phosphorylation,VEGF,eNOS,and MDA in the stroke model group increased(P<0.05);the levels of PI3K membrane translocation,AKT phosphorylation,VEGF,eNOS,and MDA in the cryptotanshinone group decreased(P<0.05),and was negatively correlated with dose(P<0.05).Compared with the control group,the levels of NO,SOD,Bcl-2,and Bax in the stroke group significantly decreased(P<0.05),and the levels of NO,SOD,Bcl-2,and Bax in the cryptotanshinone group increased(P<0.05),and were positively correlated with the dose(P<0.05).Conclusion Cryptotanshinone has a protective effect on the brain tissue of stroke rats,and its mechanism may be related to its inhibition of PI3K/AKT-eNOS signaling pathway.