瘦素对局灶性脑缺血后内质网应激相关蛋白的作用

Effects of leptin on endoplasmic reticulum stress related proteins after focal cerebral ischemia

目的探讨瘦素对大鼠局灶性脑缺血后内质网应激相关蛋白的影响。方法 SD大鼠40只,随机分为假手术组、脑缺血组、脑缺血瘦素预处理组,线栓法制备大鼠大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型,在闭塞血管前3 h皮下注射瘦素,于闭塞血管6 h后采用Longa 5分制量表进行神经功能评分、称量体重及脑水肿变化,并灌注取脑,采用免疫荧光化学法检测内质网应激相关蛋白葡萄糖调节蛋白78(glucoseregulated protein 78,GRP78)及C/EBP同源蛋白(C/EBP-homologous protein,CHOP)表达。结果脑缺血瘦素预处理组和脑缺血组体重变化未见差异(P>0.05);脑缺血瘦素预处理组神经功能评分(1.90±0.31 vs.2.50±0.52,P<0.05)和脑水肿程度(3.60±0.52 vs.7.70±0.94,P<0.001)明显轻于脑缺血组,同时脑缺血瘦素预处理组GRP78表达明显高于脑缺血组(48.69±5.06 vs.35.78±4.35,P<0.01),CHOP表达明显低于脑缺血组(38.81±5.34 vs.60.24±4.11,P<0.01)。结论瘦素可减少神经功能缺损并可能与其上调GRP78蛋白,下调CHOP蛋白来减弱脑缺血导致的内质网应激有关。

Objective To investigate the effect of leptin on endoplasmic reticulum stress related protein after focal cerebral ischemia in rats. Methods Ischemia was induced by occluding the middle cerebral artery in rats brain using the filament occlusion method. Forty SD rats were randomly divided into sham operation group, cerebral is-chemia group and leptin-preconditioning group. Leptin was injected subcutaneously before occlusion of blood vessel. Longa 5 score neurological function scale, body weight and brain edema changes were measured 6 hours after MCAO, and the brain was removed to detect the endoplasmic reticulum marker protein： glucose-regulated protein 78 （GRP78） and C/EBP-homologous protein （CHOP） by immunohistochemical method. Results There was no difference in the body weight changes between leptin-preconditioning group and ischemic group. In the leptin-preconditioning group, the neurological function score （1.90±0.31 vs. 2.50±0.52, P〈0.05） and the degree of brain edema （3.60±0.52 vs. 7.70±0.94, P〈0.001） were significantly lower than those in the cerebral ischemia group. Moreover, the expression of GRP78 in leptin-preconditioning group was significantly higher than that in ischemia group （48.69 ±5.06 vs. 35.78± 4.35, P〈0.01）, and the expression of CHOP was significantly lower than that of ischemia group （60.24 ±4.11 vs. 38.81±5.34, P〈0.01）. Conclusion Leptin can reduce the neurological deficit and may be associated with the up-reg-ulation of GRP78 protein, and down regulation of CHOP protein to weaken the endoplasmic reticulum stress caused by cerebral ischemia