氯化锂对脑出血大鼠神经细胞凋亡及脑组织含铁血红素氧合酶-1表达的影响

Effects of Lithium Chloride on Expression of Apoptosis and Heme oxygenase-1 Protein in Rats with Intracerebral Hemorrhage

目的:观察氯化锂对SD成年大鼠脑出血后神经细胞凋亡及含铁血红素氧合酶-1(HO-1)表达的影响。方法:54只SD大鼠,随机分为假手术组、脑出血组和氯化锂预处理脑出血组,每组18只。氯化锂预处理脑出血组手术前7天起每天腹腔注射1 mmol/L的氯化锂。利用立体定向技术,将一定量的Ⅳ型胶原酶用微量进样器精确注入大鼠内囊诱导脑出血模型。据术后处死动物的时间不同,各组再分别分为1、3、7天三个亚组。分别采用TUNEL和免疫组化观察脑出血区的神经细胞凋亡和HO-1的表达情况。结果:脑出血后1、3、7天,氯化锂预处理组脑血肿区的TUNEL阳性细胞明显少于相对应的脑出血组(P<0.01),而HO-1阳性细胞数则明显降低(P<0.01)。结论:氯化锂预处理能显著减少脑出血后血肿区的神经元细胞凋亡,降低HO-1的表达,发挥神经保护作用。

Objective:To observe the expression of apoptosis and heme oxygenase-1 (HO-1) protein in brains of intracerebral hemorrhage(ICH) induced by collagenase and the intervention effects of lithium chloride.Methods: 54 Sprague-Dawley male rats were randomized into sham-operation group,ICH group and lithium chloride treatment group(n=18).ICH models were made by injection of collagenase Ⅳ.Sham-operation group was instead by phosphate buffer solution.7 days before surgery,treatment group was administrated lithium chloride 1 mmol/kg by peritoneal injection once a day until rats were killed.The brain tissue specimen in every group was gathered at 1 day,3 days and 7 d after operation,respectively.The expression of apoptosis and HO-1 in rat brain after ICH was detected with TdT-mediated dUTP nick end labeling (TUNEL) and immunohistochemistry method at the same time.Results:No positive cells for apoptosis and HO-1 were found in the brain of sham-operated group.Compared with ICH group,the amount of apoptosis in brain tissue in ICH treated group were obviou sly decreased (P < 0.01).HO-1 protein expressed at 1d,peaked at 3 ds,and then lowered at 7 d after ICH.Contrast to ICH group,the lower expression of HO-1 protein in treatment group (P < 0.01).Conclusions:Lithium chloride can obviously decrease the apoptosis of neuron and expression of HO-1 protein,which may be related with its anti-apoptosis and anti-inflammtion effect following ICH.