Abstract: Objective To investigate the protective effect of adiponectin (ADPN) through PI3K/PKB signaling pathway in rats with cerebral infarction. Methods The SD rats were randomly divided into sham operation group, middle cerebral artery occlusion (MCAO) model group, ADPN treatment group and PI3K/PKB inhibitor (LY294002) group, with 15 rats in each group. The rat MCAO model was constructed by thread occlusion method, and all the rats were given reperfusion 1.5 hours after ischemia. The following treatments were given 2 hours after successful ischemia-reperfusion: the rats in the ADPN treatment group were given intravenous injection of ADPN (180 μg/100 g), the rats in the inhibitor group were given intravenous injection of ADPN (180 μg/100 g) + LY294004 (0.03 mg/100 g), and the other two groups were given the corresponding volume of 0.9% normal saline (0.09 mL/100 g). The cerebral infarct area, brain water content of rats in each group were detected 24 hours after ischemia-reperfusion. And neurological function deficit was assessed by Longa 5-point. The expression levels of PI3K, PKB, p-PKB and ADPN protein were detected by western blotting, the levels of MDA and SOD were detected by enzyme linked immunosorbent assay (ELISA). Results Compared with the sham operation group, the area of cerebral infarction, brain water content, neurological function deficit score and MDA level in MCAO model group increased (all P<0.001), and the expression levels of SOD, ADPN, PI3K and p-PKB protein decreased (all P<0.001). Compared with MCAO model group, the area of cerebral infarction, brain water content, neurological deficit score and MDA level in ADPN treatment group decreased (all P<0.001), and the expression levels of SOD, ADPN, PI3K and p-PKB protein increased (all P<0.001). Compared with ADPN treatment group, the area of cerebral infarction, brain water content, neurological function deficit score and MDA level in inhibitor group increased (all P<0.001), and the expression levels of SOD, ADPN, PI3K and p-PKB protein decreased (all P<0.001). Conclusions ADPN has a protective effect on cerebral ischemia-reperfusion injury, which may be related to activation of PI3K/PKB signal pathway and inhibition of oxidative stress.

Key words: PI3K/PKB; Adiponectin; Cerebral infarction; Cerebral ischemia reperfusion; Oxidative stress

摘要： 目的 探讨磷脂酰肌醇3激酶/蛋白激酶B（phosphatidylinositol-3-kinase/protein kinase B，PI3K/PKB）信号通路介导脂联素对脑缺血再灌注大鼠的保护作用。 方法 随机将SD大鼠分为假手术组、模型组、脂联素治疗组和PI3K/PKB抑制剂LY294002组（抑制剂组），每组15只。通过线栓法构建大脑中动脉缺血模型，缺血1.5 h后再灌注。脂联素治疗组在再灌注2 h后，给予大鼠尾静脉注射脂联素（180 μg/100 g）；抑制剂组在再灌注2 h后给予大鼠尾静脉注射脂联素（180 μg/100 g）+LY294004（0.03 mg/100 g）；假手术组和模型组尾静脉注射相应体积的0.9%生理盐水（0.09 mL/100 g）。各组缺血再灌注24 h后，检测各组大鼠脑梗死面积和脑含水量；采用Longa 5分法进行神经功能缺损评分；蛋白质印迹法（Western blotting）检测大鼠脑组织PI3K、PKB、磷酸化的蛋白激酶B（phosphorylated PKB，p-PKB）和脂联素蛋白表达水平；酶联免疫吸附（enzyme linked immunosorbent assay，ELISA）法检测大鼠血清丙二醛（malondialdehyde，MDA）和超氧化物歧化酶（superoxide dismutase，SOD）水平。 结果 与假手术组相比，模型组大鼠的脑梗死面积、脑含水量、神经功能缺损评分和MDA水平均升高（均P<0.001），SOD、脂联素、PI3K和p-PKB的表达水平均降低（均P<0.001）。与模型组比较，脂联素治疗组大鼠脑梗死面积、脑含水量、神经功能缺损评分和MDA水平均降低（均P<0.001），SOD、脂联素、PI3K和p-PKB表达水平均升高（均P<0.001）；与脂联素治疗组比较，抑制剂组大鼠脑梗死面积、脑含水量、神经功能缺损评分和MDA水平均升高（均P<0.001），SOD、脂联素、PI3K和p-PKB表达水平均降低（均P<0.001）。 结论 脂联素对脑缺血再灌注有明显保护作用，该保护机制可能与激活PI3K/PKB信号通路抑制氧化应激相关。

关键词: 磷脂酰肌醇3激酶; 蛋白激酶B; 脂联素; 脑梗死; 脑缺血再灌注; 氧化应激