补体分子调控TGFβ1/smad通路减少蛛网膜下腔出血后神经元凋亡的作用及机制  

Effect and mechanism of complement molecules regulate TGFβ1/smad pathway to reduce neuronal apoptosis after subarachnoid hemorrhage

作　　者：明圆圆 孙勇[1] 张洪伟[1] 张自园 朱贤龙[2] MING Yuanyuan;SUN Yong;ZHANG Hongwei;ZHANG Ziyuan;ZHU Xianlong(The First People’s Hospital of Lianyungang,Lianyungang 222000,China;The Second People’s Hospital of Lianyungang,Lianyungang 222002,China)

机构地区：[1]连云港市第一人民医院,江苏连云港222000 [2]连云港市第二人民医院,江苏连云港222002

出　　处：《中国实用神经疾病杂志》2024年第4期493-498,共6页Chinese Journal of Practical Nervous Diseases

基　　金：江苏省卫生健康委科研项目(编号:ZDA2020018)。

摘　　要：目的 探讨补体分子对蛛网膜下腔出血(SAH)后神经元凋亡的影响及可能的机制。方法 将90只大鼠随机分为假手术组、SAH模型组、SAH模型+补体分子组,每组30只。采用枕大池单次注射自体血的方法建立SAH模型,SAH后24 h采用Garcia评分和平衡木试验评分评定神经功能缺损程度。成功建模24 h后,称取脑组织湿质量和干质量,计算脑组织含水率。绘制伊文思蓝标准曲线,评估血-脑屏障通透性。采用免疫荧光染色观察各组小胶质细胞活化情况,蛋白质免疫印迹法(WB)检测各组补体C3、TGFβ1/smad蛋白的表达情况,TUNEL法检测神经元凋亡情况。结果 与假手术组相比,SAH模型组大鼠的Garcia评分和平衡木试验评分均降低,脑组织含水率和血-脑屏障通透性均增加,小胶质细胞活化程度增强,补体C3、TGFβ1/smad蛋白的表达水平升高,神经元凋亡率增加(P<0.05)。与SAH模型组相比,SAH模型+补体分子组大鼠的Garcia评分和平衡木试验评分均升高,脑组织含水率和血-脑屏障通透性均降低,小胶质细胞活化程度减弱,补体C3、TGFβ1/smad蛋白的表达水平降低,神经元凋亡率减少(P<0.05)。结论 补体分子可通过调控TGFβ1/smad通路抑制SAH后小胶质细胞活化,从而减少神经元凋亡,改善神经功能缺损。Objective To investigate the effect of complement molecules on neuronal apoptosis after subarachnoid hemorrhage(SAH)and its possible mechanism.Methods Ninety rats were randomly divided into sham operation group,SAH model group,and SAH model+complement molecule group,with 30 rats in each group.SAH model was established by a single injection of autologous blood into the cistern magna.Neurological function deficit was evaluated by Garcia score and balance beam test score at 24-hour after SAH.The brain tissue wet weight and dry weight were weighed,and the brain tissue water content was calculated.Evans blue standard curve was drawn to evaluate the blood-brain barrier permeability.Immunofluorescence staining was used to observe the activation of microglia in each group.Western blotting(WB)was used to detect the expression of complement C3,TGFβ1/smad protein in each group.TUNEL method was used to detect neuronal apoptosis.Results Compared with sham operation group,the Garcia score and balance beam test score of SAH model group decreased,the brain tissue water content and blood-brain barrier permeability increased,the activation degree of microglia enhanced,the expression levels of complement C3,TGFβ1/smad protein increased,and the neuronal apoptosis rate increased(P<0.05).Compared with SAH model group,the Garcia score and balance beam test score of SAH model+complement molecule group increased,the brain tissue water content and blood-brain barrier permeability decreased,the activation degree of microglia weakened,the expression levels of complement C3,TGFβ1/smad protein decreased,and the neuronal apoptosis rate decreased(P<0.05).Conclusion Complement molecules can regulate TGFβ1/smad pathway to inhibit microglial activation after SAH,thereby reducing neuronal apoptosis and improving neurological function deficit.

关 键 词：蛛网膜下腔出血 补体分子 神经元凋亡 TGFβ1/smad通路 大鼠 

分 类 号：R-332[医药卫生]