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

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。

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.