左归降糖解郁方对糖尿病并发抑郁症大鼠海马血脑屏障精细结构AQP4、Cx43的影响  

Effects of Zuogui Jiangtang Jieyu Formula on the expressions of AQP4,Cx43 in hippocampal blood-brain barrier 's fine structure in diabetes mellitus rats with depression

作　　者：王宇红[1,2] 谭小雯[1] 曾嵘[1] 柴上 杨蕙[3] 孟盼 张秀丽 

机构地区：[1]湖南中医药大学,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 [3]湖南中医药大学第一附属医院,湖南长沙410007

出　　处：《中成药》2015年第10期2109-2114,共6页Chinese Traditional Patent Medicine

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

摘　　要：目的研究左归降糖解郁方(黄芪、贯叶连翘、姜黄、熟地黄、山茱萸等)对糖尿病并发抑郁症大鼠海马血脑屏障精细结构水通道蛋白AQP4和缝隙连接蛋白Cx43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、28 d慢性应激联合的方法复制糖尿病并发抑郁症大鼠模型,并随机分为5组:模型组,阳性药(二甲双胍+盐酸氟西汀)组,左归降糖解郁方高、中、低剂量组,以正常大鼠为空白组,灌胃给药4周。给药后,采用Morris水迷宫测试大鼠空间学习能力,HE染色法观察海马组织病理学,免疫组化法检测海马血脑屏障精细结构AQP4和Cx43表达情况。结果与空白组比较,模型组大鼠逃避潜伏期延长(P<0.01),海马细胞存在明显损伤,AQP4和Cx43表达下降,差异有统计学意义(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逃避潜伏期缩短,差异有显著统计学意义(P<0.01),海马细胞形态趋于正常,且AQP4和Cx43表达增多,差异有统计学意义(P<0.05)。结论左归降糖解郁方对糖尿病并发抑郁症大鼠的治疗作用可能与调控海马血脑屏障精细结构AQP4和Cx43表达有关。AIM To investigate the effects of Zuogui Jiangtang Jieyu Formula（ ZJJF）（ Astragali Radix,Hypericum perforatum Linn.,Curcumae longae Rhizoma,Rehmanniae Radix praeparata,Corni Fructus,etc.） on the expressions of aquaporin 4（ AQP4） and connexin 43（ Cx43） in hippocampal blood-brain barrier＇s fine structure 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,and chronic stress. The model rats were randomly divided into five groups： the DM with depression group,positive drug group（ metformin ＋ fluoxetine）,high-,mid-,and low-dose ZJJF groups; another untreated 10 rats were used as the blank group. After four weeks of administration,Morris water maze was used to detect the cognition of the rats; the expressions of AQP4 and Cx43 in rat hippocampul blood-brain barrier were detected by immunocytochemistry. Hippocampal morphology was observed by HE staining. RESULTS As compared with the blank group,model rats＇ escape latency was significant longer（ P〈0. 01）,hippocampal cells were damaged; the expressions of AQP4 and Cx43 decreased（ P〈0. 05）. Compared with the model group,the escape latency in positive drug group and high dose-ZJJF group was significantly shorter（ P〈0. 01）; hippocampal cells became normal; the expressions of AQP4 and Cx43 increased（ P〈0. 05）.CONCLUSION The therapeutic mechanism of ZJJF for diabetic rats with depression may be related to the regulation of the expressions of AQP4 and Cx43 in hippocampal blood-brain barrier＇s fine structure.

关 键 词：左归降糖解郁方 大鼠 糖尿病并发抑郁症 海马 水通道蛋白AQP4 缝隙连接蛋Cx43 

分 类 号：R285.5[医药卫生—中药学]