左归降糖解郁方对糖尿病并发抑郁症大鼠海马血脑屏障紧密连接蛋白、IV型胶原蛋白和α-平滑肌肌动蛋白表达的影响  

Effects of Zuogui Jiangtang Jieyu Formula on protein expression of CoIV, ZO-1, and α-SMA in hippocampal blood-brain barrier of diabetes mellitus rats with depression

作　　者：杨蕙[1] 杜青 赵洪庆 谭小雯 孟盼 王宇红 

机构地区：[1]湖南中医药大学第一附属医院,湖南长沙410007 [2]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,湖南长沙410007

出　　处：《中草药》2015年第21期3214-3218,共5页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81373578,81403379);湖南省自然科学基金项目(13JJ5030);湖南省科技厅科技计划项目(2012SK3141)

摘　　要：目的研究左归降糖解郁方对糖尿病并发抑郁症(DD)大鼠海马血脑屏障紧密连接蛋白(ZO-1)、IV型胶原蛋白(Co IV)、α-平滑肌肌动蛋白(α-SMA)表达的影响。方法采用ig高脂乳剂、尾iv链脲佐菌素(STZ,38 mg/kg)、28 d慢性应激联合的方法建立DD大鼠模型并随机分为5组:模型组,阳性药(盐酸二甲双胍0.18 g/kg+百忧解1.8 mg/kg)组,左归降糖解郁方高、中、低剂量(32.82、16.41、8.20 g/kg)组,并以正常大鼠为对照组,每组10只。给药4周后,电镜下观察血脑屏障的形态变化,免疫组化法检测海马血脑屏障Co IV、ZO-1、α-SMA的表达情况。结果与对照组比较,模型组大鼠ZO-1、α-SMA的表达下降,Co IV的表达升高,差异显著(P<0.05);与模型组比较,阳性药组和左归降糖解郁方高剂量组大鼠ZO-1、α-SMA的表达升高,Co IV的表达下降,差异显著(P<0.05、0.01)。结论左归降糖解郁方可以保护DD大鼠血脑屏障的损伤,其保护机制可能与升高血脑屏障ZO-1和α-SMA的表达,降低Co IV的表达有关。Objective To investigate the effects of Zuogui Jiangtang Jieyu Formula（ZJJF） on protein expression of Co IV, ZO-1, and α-SMA in hippocampal blood-brain barrier（BBB） in diabetes mellitus（DM） rats with depression. Methods DM rat model with depression was established by the combination of high-fat diet, injection of Streptozotocin（STZ, 38 mg/kg）, and chronic stress. The model rats were randomly divided into five groups, DM with depression group, metformin（0.18 g/kg） ＋ fluoxetine（1.8 mg/kg） group, high-, mid-, and low-dose（32.82, 16.41, and 8.20 g/kg） ZJJF groups（n = 10）. After 4 weeks of administration, the morphological changes of BBB were observed under the electron microscope, the expression of Co IV, ZO-1, and α-SMA in rat hippocampul BBB was detected by immunocytochemistry. Results Compared with the control group, the expression of ZO-1 and α-SMA in the model group was decreased（P 〈 0.05）, and the expression of Co IV was increased（P 〈 0.05）. Compared with the model group, the expression of ZO-1 and α-SMA in metformin ＋ fluoxetine group and high-dose ZJJF group was increased（P 〈 0.05, 0.01）, and the expression of Co IV was decreased（P 〈 0.05）. Conclusion ZJJF could repair the damage of BBB in DM rats with depression, and the mechanism may be related to the expression regulation of Co IV, ZO-1, and α-SMA.

关 键 词：左归降糖解郁方 糖尿病并发抑郁症 紧密连接蛋白 IV型胶原蛋白 α-平滑肌肌动蛋白 

分 类 号：R285.5[医药卫生—中药学]