刺芒柄花素对脑缺血再灌注损伤大鼠的保护作用及其机制研究

Protective Effects and Mechanism Study of Formononetin on Cerebral Ischemia-reperfusion Injury in Rats

关键词:  刺芒柄花素  脑缺血再灌注  凋亡  氧化应激

Key words:  formononetin  cerebral ischemia-reperfusion injury  apoptosis  oxidative

摘要:

目的 研究刺芒柄花素（formoononetin，FOR）对脑缺血再灌注损伤（cerebral ischemia-reperfusion injury，I/R）大鼠的保护作用，并探讨其可能的机制。方法 SD大鼠50只，♂，分为假手术组、I/R组、FOR高、中、低剂量组（100，50，20 mg·kg^-1）。连续灌胃给药7 d后，除假手术组外均采用MCAO法造成大鼠脑缺血模型，2 h后拔出线栓，再灌注24 h后进行神经功能评分；跳台法检测大鼠学习记忆能力；HE染色法观测脑组织病理形态；ELISA法检测血清中NO表达及NOS活性水平；Western blot法检测脑组织中caspase-3、Bcl-2和Bax蛋白的表达。结果 与I/R组相比，FOR高、中、低剂量组能显著降低大鼠神经功能评分（P<0.01）、提高大鼠学习记忆能力（P<0.05或P<0.01）、改善脑组织形态、降低血清中NO表达水平及NOS活性（P<0.01）、降低caspase-3蛋白和Bax蛋白的表达水平并提高Bcl-2的表达水平（P<0.01）。结论 刺芒柄花素对I/R大鼠具有一定的保护作用，其机制可能与抗氧化应激和抗凋亡有关。

Abstract:

OBJECTIVE To study the protective effects of formononetin (FOR) on cerebral ischemia-reperfusion injury (I/R) in rats and explore its possible mechanism. METHODS Fifty male SD rats were divided into 5 groups:sham operation group, I/R group, FOR high, medium and low dose group (100, 50, 20 mg·kg^-1). Continuous intragastric administration for 7 d, MCAO model was used to make I/R rats. After 2 h, plug was pulled out and after 24 h blood were perfused to form the model of I/R, the neurological score was detected;the ability of learning and memory was detected by step-down test;pathological morphology was observed by HE;NO expression and NOS activity in serum was detected by ELISA;the expression of caspase-3, Bcl-2 and Bax protein in brain tissues was detected by Western blot method. RESULTS Compared with I/R group, FOR high, middle and low dosage groups could significantly reduce the rat nerve function score (P<0.01), improve the ability of learning and memory of rats (P<0.05 or P<0.01), improve the morphology of brain tissue, decrease the NOS activity level and expression of NO in serum (P<0.01), reduce caspase-3 and Bax protein expression level and improve the expression level of Bcl-2(P<0.01). CONCLUSION It is possible that FOR can protect I/R rats, and its mechanism maybe related to anti-oxidative stress and anti-apoptosis.