瘦素对小鼠局灶性脑缺血再灌注损伤的保护作用

Protective effect of leptin against cerebral ischemia/reperfusion injury in mice

目的探讨瘦素对局灶性脑缺血再灌注损伤的保护作用及其机制。方法线拴法制备小鼠大脑中动脉局灶性脑栓塞模型,缺血2h再灌注24h后评价神经功能状态,TTC染色测定脑梗死体积;采用比色法测定缺血侧脑组织匀浆乳酸脱氢酶(LDH)、丙二醛(MDA)和一氧化氮(NO)含量;HE染色观察组织病理学改变,免疫组化法测定脑组织胶质纤维酸性蛋白质GFAP表达。结果瘦素能明显改善神经功能状态,缩小脑缺血再灌注后脑梗死体积,降低脑组织LDH、MDA、NO含量,同时减轻脑组织病理学损伤程度,维持星形胶质细胞正常细胞形态,上调GFAP表达水平。结论瘦素对小鼠脑缺血再灌注损伤具有明显保护作用,其机制与抗氧化损伤、清除自由基和调节星形胶质细胞适度增生有关。

Objective To investigate the protective effect of leptin against cerebral ischemia/reperfusion injury in mice. Methods Mouse models of transient focal cerebral ischemia were established by occlusion of the right middle cerebral artery for 2 h followed by 24 h reperfusion. The infarct volume and neurological deficit scores following leptin treatment were determined using TTC staining and the Longa＇s score, respectively, to evaluate the protective effect of leptin against ischemic cerebral injury. The levels of lactate dehydrogenase （LDH）, malondialdehyde （MDA） and nitric oxide （NO） in the brain tissue were measured by colorimetry. The histopathological changes in the brain were observed with HE staining, and the expression of glial fibrillary acidicprotein （GFAP） was detected by immunohistochemistry. Results Leptin treatment markedly reduced cerebral infarct volume and neurological deficits induced by transient ischemia. The LDH, MDA and NO levels in the brain tissues were significantly decreased after leptin treatment, which also alleviated the histopathological injury, maintained the normal morphology of the astrocytes and increased the expression of GFAP. Conclusion Leptin produces obvious protective effect against cerebral ischemia/reperfusion injury by inhibiting lipid peroxidation, stabilizing the internal environment and adjusting the activity of the astrocytes.