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(CoIV)、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CoIV、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,CoIV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,CoIV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CoIV的表达有关.

Objective To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZJJF) on protein expression of CoIV, 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 CoIV, 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 CoIV 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 CoIV 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 CoIV, ZO-1, and α-SMA.

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)