大豆异黄酮减轻大鼠脑缺血-再灌注损伤

Soybean isoflavone reduces cerebral ischemia-reperfusion injury in rats

目的研究大豆异黄酮(SI)对大鼠脑缺血-再灌注(I/R)损伤保护作用的分子机制。方法将大鼠随机分为假手术组(sham)、模型组(I/R),分别制作脑缺血-再灌注模型和大豆异黄酮(SI)干预组(50、100和200mg/kg)。2,3,5-氯化三苯基四氮唑(TTC)染色法检测脑梗死体积;HE染色检测脑组织病理变化;ELISA测定脑组织中超氧化物歧化酶SOD活性,测定IL-6、TNF-α、cAMP含量;Westernblot检测皮层p-ERK1/2的表达。结果与sham组相比,I/R组出现明显的梗死灶(P<0.05);SI干预组(100和200mg/kg)脑梗死灶体积明显降低(P<0.05)。模型组细胞间隙增宽,细胞核固缩,SI干预组神经细胞的病理变化有所改善。与sham组相比,I/R组脑组织中SOD活性和cAMP含量显著降低,SI干预组(100和200mg/kg)脑组织中SOD活性和cAMP含量升高(P<0.05);与sham组相比,I/R组IL-6和TNF-α含量均显著升高,SI干预组(100和200mg/kg)IL-6和TNF-α的含量明显降低(P<0.05)。与sham相比,I/R组中p-ERK1/2表达升高,SI干预组(100和200mg/kg)p-ERK1/2表达降低(P<0.01)。结论SI能够有效改善大鼠脑I/R引起的氧化应激及炎性反应,提示SI对大鼠脑I/R的保护作用机制可能与SI抗氧化及炎性反应有关。

Objective To study the molecular mechanism of protective effects of soybean isoflavones (SI) on cerebral ischemia-reperfusion (I/R) injury in rats. Methods Rats were randomly divided into sham operation group (sham), ischemia-reperfusion group (I/R), soybean isoflavones (SI) intervention group(50, 100 and 200 mg/kg). 2,3,5-triphenylte-trazolium chloride (TTC) staining method was used to detect the cerebral infarction volume. HE staining was used to detect the pathological changes of brain tissues. The activity of superoxide dismutase SOD and the contents of IL-6, TNF-α, cAMP were measured by ELISA. Western blot was used to detect the level of p-ERK1/2 . Results The I/R group had obvious infarct foci as compared to the sham group ( P <0.05), but the cerebral infarct volume significantly decreased after SI intervention(100 and 200 mg/kg)( P <0.05), respectively. In model group, cell gap was widened and nucleus became pyknosis. After the intervention of SI group, the pathological changes of cells were improved. Compared with the sham group, the activity of SOD and the content of cAMP in I/R group were significantly reduced, but after SI intervention (100 and 200 mg/kg), the activity of SOD and the content of cAMP were increased ( P <0.05). Compared with the sham group, the content of IL-6 and TNF-α in I/R group increased, but they decreased after intervented with SI(100 and 200 mg/kg )( P <0.05). Compared with the sham group, the expression of p-ERK1/2 in the model group was increased, and the expression of p-ERK1/2 decreased after SI intervention (100 and 200 mg/kg)( P < 0.01). Conclusions SI can effectively improve oxidative stress and inflammatory response induced by I/R in rats. It is suggested that the protective mechanism of SI on cerebral I/R in rats might be related to the antioxidant and inflammatory reaction of SI.