| Objective:1.To study diabetes mellitus with depression rats’hippocampal blood-brain barrier damage mechanisms from microscopic morphology to molecular level.2. To explore the therapeutic mechanism of Zuo Gui Jiang Tang Jie Yu prescription, what was a traditional Chinese medicine compound prescription on the animal model of diabetes mellitus with depression, and to further clarify the effect by protecting hippocampus brain barrier damage. This study will lay the foundations for diabetes mellitus with depression experimental study.Method:1.Studying damage mechanisms of diabetes mellitus with depression rats’ hippocampal blood-brain barrier.SD rats were fed a high fat diet for14days before the tail vein injection of streptozotocin (38mg/kg). Then they were randomly divided into2groups according to their behavior, the diabetes group and diabetes mellitus with depression group; the normal rats were also randomly divided into2groups according to their behavior, normal group and depression group. Measured the body weight,fasting plasma glucose of rats in each group.Open-field test and Morris water maze were used to evaluate the activity of rats.Blood lipids were assayed by biochemical techniques. Plasma of CRH, ACTH, CORT level and serum S100B content were detected by ELISA method. Pancreas and hippocampal blood-brain barrier morphological changes were observed by HE staining and transmission electron microscopy. ZO-1, CoIV, a-SMA, AQP4, Cx43expression were detected by immunohistochemistry in hippocampal blood-brain barrier.2. The effect of Zuo Gui Jiang Tang Jie Yu prescription.The diabetes mellitus with depression rats were randomly divided into five groups, the diabetes mellitus with depression group, metformin combined fluoxetine group, Zuo Gui Jiang Tang Jie Yu prescription high, medium and low dose group. After4weeks, the rats indicators were detected according to the method1.Results:1. Compared with the normal group, diabetes mellitus with depression rats body weight decreased; significantly reduce the total number of active Open-field test; Morris water maze test escape latency was significantly longer,which indicated cognitive dysfunction; blood biochemical indicators, glucose increased, glycosylated hemoglobin, cholesterol, triglycerides and low-density lipoprotein were significantly higher, and the high-density lipoprotein was significantly lower.Plasma CRH, ACTH, CORT, S100B was significantly higher; HE staining revealed the number of pancreatic islet reducing, size became smaller, fuzzy boundaries, pancreatic islet B cells arranged in a sparse, number of cells decreased and vacuoles degeneration;transmission electron microscopy revealed that the hippocampus brain barrier presents capillary stenosis, endothelial blur,edema surrounding glial cells eventually foot; immunohistochemical detection of hippocampal BBB-related proteins found the ZO-1, CoⅣ, a-SMA, AQP4, Cx43expression was significantly abnormal2. Compared with the model group, Zuo Gui Jiang Tang Jie Yu prescription high dose group were significantly increased the number of locomotor activity; Morris water maze test escape latency decreased, cognitive function was restored to some extent, blood biochemical indicators end to stabilize and blood plasma CRH, ACTH, CORT, S100B levels were significantly lower, morphological changes in pancreatic islet and hippocampal blood-brain barrier tend to normalization associated protein ZO-1, CoIV, a-SMA, AQP4, Cx43expression in hippocampal brain barrier was corrected disorder:and which middle dose and low-dose effect were weak. Conclusion:1.Diabetes mellitus with depression rats presented hippocampal blood-brain barrier damage. Not only the transmission electron microscope observed significant morphological changes;did immunohistochemical detect associated protein disorders, which suggesting that impaired barrier function.2.The Zuo Gui Jiang Tang Jie Yu prescription can adjust weight and behavior of the model rat, improve blood glucose,blood lipids,HPA axis hyperactivity, reduce pancreatic islet and hippocampal blood-brain barrier damage. Its therapeutic effect may be related to regulating the barrier function of the hippocampus brain barrier:increased ZO-1,α-SMA, AQP4, Cx43expression, reducing CoIV expression. Zuo Gui Jiang Tang Jie Yu prescription showed a certain effect, worthy of further research and development.
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