左归降糖解郁方对糖尿病并发抑郁症大鼠海马Bcl-2,Bax,Caspase 8蛋白表达的影响  

Effects of Zuogui Jiangtang Jieyu Prescription on Expression of Bcl-2,Bax,Caspase 8 in Hippocampus of Diabetes Mellitus Rats with Depression

作　　者：王宇红 柴上 谭小雯 杨蕙[2] 孟盼 张秀丽 

机构地区：[1]湖南省中药粉体与创新药物省部共建国家重点实验室培育基地,长沙410007 [2]湖南中医药大学第一附属医院,长沙410007

出　　处：《中国实验方剂学杂志》2015年第3期106-109,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81373578;81403379);湖南省自然科学基金项目(13JJ5030);湖南省高校创新平台开放基金项目(13k074)

摘　　要：目的:探讨左归降糖解郁方(ZJJF)对糖尿病并发抑郁症(diabetes mellitus with depression,DD)大鼠海马B细胞淋巴瘤/白血病-2(Bcl-2),Bcl-2相关X蛋白(Bax),半胱-天冬氨酸蛋白酶8(Caspase 8)蛋白表达的影响。方法:采用高脂乳剂灌胃、尾静脉注射链脲佐菌素(STZ,38 mg·kg-1)与慢性应激联合的方法复制DD模型,并随机分为3组:模型组,阳性药(二甲双胍0.18 g·kg-1+氟西汀0.0018 g·kg-1)组,ZJJF(32.82 g·kg-1)组,ig给药4周后,采用旷场实验(OFT)实验,观察各组大鼠行为学改变;采用蛋白免疫印迹法(Western blotting)检测模型大鼠海马Bcl-2,Bax,Caspase 8蛋白的表达。结果:与正常组比较,模型组大鼠OFT实验中活动总数明显减少(P<0.01);与模型组比较,阳性药和ZJJF(32.82 g·kg-1)组大鼠自主活动次数明显增多(P<0.01)。与正常组比较,模型组大鼠海马Bcl-2蛋白表达下降(P<0.05),Bax,Caspase8蛋白表达显著升高(P<0.01)。与模型组比较,阳性药组海马Bcl-2蛋白表达升高(P<0.05),Bax,Caspase 8蛋白表达显著降低(P<0.01)。与模型组比较,ZJJF(32.82 g·kg-1)组海马Bcl-2表达升高(P<0.05),Bax,Caspase 8表达降低(P<0.05,P<0.01)。结论:ZJJF可改善糖尿病并发抑郁症大鼠抑郁行为异常,该作用可能与抑制神经细胞凋亡,保护海马有关。Objective： To investigate the effects of Zuogui Jiangtang Jieyu （ZJJF） prescription on expression of Bcl-2, Bax and cysteinecontaining asparate specific protease （caspase 8 ） in Hippocampus of diabetes mellitus rats with depression （ DD）. Method： DD model was established by the combination of high-fat diet, injection of streptozotocin （STZ, 38 mg ·kg^-1） , and chronic stress. The model rats were randomly divided into three groups, the DD group, metformin （0. 18 g ·kg^-1） combined fluoxetine （0. 0018 g ·kg^-1） group and ZJJF （32.82 g ·kg^-1） groups . After 4 weeks of administration, the behavior were observed by the open-field test （OFT） test; Western-blotting was used to detect the expression of B cell lymphoma/leukemia 2 （Bcl-2）, Bcl-2- associated X protein （Bax） and Caspase 8 protein on hippocampal. Result： Compared with the normal group, the locomotor activity of model group were significantly reduced （P 〈 0.01）. Compared with the model group, the locomotor activity of rats in ZJJF （32.82 g ·kg^-1 ） and metformin （0.18 g ·kg^-1 ） combined fluoxetine （0. 0018 g ·kg^-1） groups were significantly increased （P 〈0.01 ）. Compared with the normal group, The Bax and Caspase 8 expression of hippocampal were significantly increased （P 〈 0. O1 ） and Bcl-2 was reduced （P 〈 0.05 ） in model group through Western-blotting. Compared with the model group, the average level of hippocampal Bcl-2 was increased （P 〈 0.05） and the Bax and Caspase 8 were significantly reduced （P 〈 0.01 ） in positive drug group. Compared with-the model group, the Bax and Caspase 8 expression were decreased （P 〈 0.05, P 〈 0.01） and Bcl-2 was increased （P 〈 0.05） in ZJJF （32.82 g·kg^-1）. Conclusion： The depressive behavior could be improved by ZJJF, which might be correlated to the inhibition of neuronal apoptosis for protecting the hippocampal.

关 键 词：糖尿病并发抑郁症 左归降糖解郁方 B细胞淋巴瘤/白血病-2 Bcl-2相关X蛋白 半胱-天冬氨酸蛋白酶8 

分 类 号：R285.5[医药卫生—中药学]