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目的:研究大豆异黄酮(Soybean Isoflavone,SI)对大鼠局灶性脑缺血再灌注损伤的保护作用,并探讨其作用机制。方法:采用线栓法制备局灶性脑缺血再灌注大鼠模型,选取120只随机分为6组:局灶性脑缺血再灌注模型组、大豆异黄酮(20、40、80和160 mg/kg)腹腔注射预处理组和舒血宁注射液(4mg/kg)阳性对照组,并设假手术组。再灌注6h后,采用盲法进行神经功能评分,测定脑梗死体积(IV%)及脑组织含水量;通过HE染色法观察脑组织病理形态学改变,通过TUNEL染色观察神经细胞凋亡状况并计算凋亡指数(Apoptosis Index,AI);通过生化分析仪测定血清中肌酸激酶(CK)、乳酸脱氢酶(LDH)含量;检测脑组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活性和丙二醛(MDA)含量。结果:与假手术组相比,局灶性脑缺血再灌注模型组大鼠出现明显的行为障碍,脑梗死体积(IV%)和脑组织含水量显著升高,脑组织出现明显的病理性改变,神经细胞凋亡状况加重,凋亡指数显著升高;血清中CK,LDH含量显著升高,脑组织中SOD、GSH-Px、CAT活性显著降低且MDA含量显著升高,差异均具有统计学意义。与局灶性脑缺血再灌注模型组相比,大豆异黄酮(40、80和160 mg/kg)组大鼠行为障碍明显好转,大豆异黄酮(80和160 mg/kg)组脑梗死体积和含水量均显著降低;大豆异黄酮预处理组大鼠脑组织病变和神经细胞凋亡均明显减轻,以160 mg/kg组效果最为显著,大豆异黄酮(80和160 mg/kg)组凋亡指数显著降低;大豆异黄酮(40、80和160 mg/kg)组大鼠血清中CK,LDH含量和脑组织中MDA含量均显著降低;大豆异黄酮(80和160 mg/kg)组脑组织中SOD、CAT活性显著降低,且160mg/kg组GSH-Px活性显著降低。结论:大豆异黄酮能够有效改善局灶性脑缺血大鼠神经功能障碍、降低脑梗死体积和脑组织含水量、改善脑组织病变和神经细胞凋亡状况,提示大豆异黄酮对大鼠局灶性脑缺血再灌注损伤具有剂量依赖性的保护作用,其作用机制可能与大豆异黄酮能够有效改善抗氧化酶活性、提高机体清除自由基能力、抑制氧化应激损伤有关。
Objective: To study the protective effect of Soybean Isoflavone (SI) on focal cerebral ischemia-reperfusion injury in rats and its mechanism. Methods: Focal cerebral ischemia-reperfusion rat model was established by thread occlusion method. One hundred and twenty rats were randomly divided into six groups: focal cerebral ischemia-reperfusion model group, soy isoflavones (20, 40, 80 and 160 mg / kg) were injected intraperitoneally into the pretreatment group and shuxuening injection (4mg / kg) for the positive control group, and sham operation group was established. After 6h of reperfusion, the nerve function was evaluated by blinded method, the volume of cerebral infarction (IV%) and the water content of brain tissue were measured. The pathological changes of brain tissue were observed by HE staining and the apoptosis of nerve cells was observed by TUNEL staining (Apoptosis Index, AI). Serum creatine kinase (CK) and lactate dehydrogenase (LDH) were measured by biochemical analyzer. The levels of superoxide dismutase (SOD) and glutathione Oxidase (GSH-Px), catalase (CAT) activity and malondialdehyde (MDA) content. Results: Compared with the sham-operation group, the rats in the model group showed obvious behavioral disturbance. The volume of cerebral infarction (IV%) and water content of brain tissue increased significantly, and the pathological The apoptosis index increased significantly, the content of CK and LDH in serum increased significantly, the activity of SOD, GSH-Px and CAT decreased significantly and the content of MDA in brain increased significantly, the difference was statistically significant Significance of learning. Compared with the focal cerebral ischemia / reperfusion model group, behavioral disorders were significantly improved in the soy isoflavones (40, 80 and 160 mg / kg) group, while those in the soy isoflavones (80 and 160 mg / kg) And water content significantly decreased. Soybean isoflavone preconditioning group rats brain tissue lesions and neuronal apoptosis were significantly reduced, 160 mg / kg group was the most significant effect, soy isoflavones (80 and 160 mg / kg) group withered The index of death was significantly decreased; the content of CK and LDH in serum and the content of MDA in brain tissues were significantly decreased in soy isoflavones (40, 80 and 160 mg / kg) The activities of SOD and CAT in the tissue were significantly decreased, and the activity of GSH-Px in 160mg / kg group was significantly decreased. CONCLUSION: Soy isoflavones can effectively improve the neurological dysfunction, reduce the volume of cerebral infarction and water content of brain tissue, improve the pathological changes of brain tissue and the apoptosis of nerve cells in focal cerebral ischemia rats. Cerebral ischemia-reperfusion injury has a dose-dependent protective effect, its mechanism may be related to soy isoflavones can effectively improve antioxidant enzyme activity, improve the body’s ability to scavenge free radicals, inhibition of oxidative stress injury.