免疫抑制剂治疗对阿尔茨海默病大鼠海马自噬蛋白Beclin-1和LC3表达的影响  

Effect of Immunosuppressive Therapy on Autophagy Protein Beclin-1 and LC3 in Hippocampus of Rats with Alzheimer’s Disease

作　　者：王晓平[1] 黄斌[1] 马帅 黄睿[1] 李晓佳[1] Wang Xiaoping;Huang Bin;Ma Shuai(Department of Neurology,Sichuan People’s Hospital,Chengdu 610072,China)

机构地区：[1]四川省人民医院神经内科,成都610072

出　　处：《华中科技大学学报（医学版）》2020年第4期450-454,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：四川省卫生计生委科研课题资助项目(No.16PJ427)。

摘　　要：目的分析免疫抑制剂治疗对阿尔茨海默病大鼠海马自噬蛋白Beclin-1与微管相关蛋白1轻链3(microtubule associated protein 1 light chain 3,LC3)表达的影响。方法将雄性SD大鼠采用Aβ25-35侧脑室注射法制备阿尔茨海默病模型大鼠,将制备的阿尔茨海默病大鼠随机分为4组:模型组、吗替麦考酚酯高剂量组(0.8 g/kg)、吗替麦考酚酯低剂量组(0.4 g/kg)和阳性药多奈哌齐组(0.5 g/kg)。对照组与模型组给予生理盐水,吗替麦考酚酯高剂量组、吗替麦考酚酯低剂量组和阳性药多奈哌齐组均给予对应药物灌胃处理,所有大鼠连续给药4周,检测所有大鼠的识别指数、水迷宫实验、小脑Tunel染色及采用Western blot实验分析海马组织的Beclin-1与LC3蛋白表达。结果与对照组比较,模型组的识别指数和穿环次数明显降低(均P<0.05),潜伏期和游泳距离明显增加(均P<0.05);与模型组比,吗替麦考酚酯低剂量组、高剂量组和阳性药组的识别指数和穿环次数明显增加(均P<0.05),潜伏期和游泳距离明显降低(均P<0.05)。镜下显示,凋亡的小脑神经细胞呈棕色,与对照组比较,模型组凋亡的小脑神经细胞明显增多;与模型组比较,吗替麦考酚酯低剂量组、高剂量组和阳性药组凋亡的小脑神经细胞明显减少。与对照组比较,模型组大鼠海马的Beclin-1和LC3表达明显降低(均P<0.05);与模型组比较,吗替麦考酚酯低剂量组、高剂量组和阳性药组Beclin-1和LC3表达明显增加(均P<0.05),且吗替麦考酚酯组中,凋亡的小脑神经细胞减少及Beclin-1和LC3表达增高均呈剂量依赖性趋势。结论吗替麦考酚酯可以改善阿尔茨海默病大鼠的学习认知能力,其机制可能与增强自噬水平和提高自噬蛋白Beclin-1和LC3表达相关。Objective To analyze the effect of immunosuppressive therapy on autophagy protein Beclin-1 and microtubule associated protein 1 light chain 3(LC3)in hippocampus of Alzheimer’s disease rats.Methods Alzheimer’s disease rat models were prepared by Aβ25-35 lateral ventricle injection in male Sprague-Dawley rats.The Alzheimer’s disease rats were randomly divided into 4 groups:model group,high-dose mycophenolate mofetil group(0.8 g/kg),low-dose mycophenolate mofetil group(0.4 g/kg)and donepezil group(0.5 g/kg).The control group and the model group were given normal saline,the high-dose mycophenolate mofetil group,the low-dose mycophenolate mofetil group and donepezil group were given the corresponding drugs.All the rats had been administered for 4 weeks.The identification index was detected,and water maze test,cerebellar Tunel staining were performed,and Beclin-1 and LC3 protein expression in hippocampus was detected by Western blotting.Results The recognition index and the frequency of piercing cycles were significantly lower(P<0.05),and the latency and swimming distance were significantly higher in the model group than in the control group(P<0.05).Compared with the model group,the recognition index and the frequency of piercing cycles of 2 mycophenolate mofetil groups and the positive drug group were significantly increased(P<0.05),and the latency and swimming distance were significantly decreased(P<0.05).The microscopic cerebellar nerve cells were brown under the microscope.Compared with the model group,the apoptotic cerebellar nerve cells of the mycophenolate mofetil low-dose and high-dose groups and the positive drug group were significantly reduced(P<0.05).Compared with the control group,the expression of Beclin-1 and LC3 in the hippocampus of the model group was significantly decreased(P<0.05).Compared with the model group,the expression of the Beclin-1 and LC3 in the mycophenolate mofetil low-dose and high-dose groups and the positive drug group were significantly increased(P<0.05).The decrease of apopto

关 键 词：免疫抑制剂 吗替麦考酚酯 阿尔茨海默病 海马 自噬 BECLIN-1 微管相关蛋白1轻链3 

分 类 号：R339.1[医药卫生—人体生理学]