Diabetes Complicated With Depression Animal Model And Traditional Chinese Medicine Intervention

Objective:1. To establish an animal model of diabetes mellitus with depression, and to establish a model evaluation system from the perspective of surface characteristics, behavior and hematology.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 of its hypoglycemic, lipid-lowering and anti-depression. This study will lay the foundations for diabetes mellitus with depression experimental study.Method:1. Building an animal model of diabetes mellitus with depression. SD rats were received a high fat diet for14days before the intraperitoneal injection of streptozotocin (38mg/kg). Then they were randomly divided into2groups according to their behavior, the diabetes group and diabetes combined with chronic stress group; the normal rats were also randomly divided into2groups according to their behavior, normal group and chronic stress group. Measured the body weight of rats in each group after28days chronic stress.Open-field test and Morris water maze were used to evaluate the activity of rats. Blood glucose, blood lipids and insulin were assayed by biochemical techniques. Plasma of CRH, ACTH and CORT level were detected by ELISA method. HE staining was used to observe the hippocampus, hypothalamus, pituitary and adrenal pathological changes of rats. Immunohistochemistry and western-blotting were used to detect the expression of GR and11(3-HSD1protein on hippocampal. RT-PCR were used to detect the expression of GR and11β-HSD1mRNA.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 indicators of established evaluation system were used to measured for rats in each group.Results:1. Compared with the normal group, the body weight of diabetic model+chronic stress rats were significantly reduced, the total number of open-field test activities were significantly reduced, the escape latency was significantly longer in the Morris water maze test, as well as the space exploration time was significantly shortened. Blood glucose, glycosylated hemoglobin, insulin, cholesterol, triglycerides and low-density lipoprotein were significantly higher, and the high-density lipoprotein was significantly lower. Plasma CRH, ACTH, CORT were significantly higher. HE staining observed that the hippocampus, hypothalamus, pituitary, adrenal existed the significant pathological changes. The11β-HSD1 expression was significantly increased and GR expression was significantly reduced in hippocampal through immunohistochemistry and Western-blotting. The results of RT-PCR were consistented with Western-blotting.2. Compared with the normal group, the indicators of model group were significantly abnormal. Compared with the model group, the locomotor activity of high dose group rats with Zuo Gui Jiang Tang Jie Yu prescription were significantly increased, and the learning and memory capacity to be a certain degree of recovery. Blood glucose was significantly stable, insulin levels and glycosylated hemoglobin were significantly lower, cholesterol, triglycerides, low-density lipoprotein levels were significantly decreased, high-density lipoprotein levels were significantly elevated. The plasma CRH, ACTH, CORT levels were significantly lower, the hypothalamus, pituitary, adrenal and hippocampal pathological changes were reduced, HPA axis hyperactivity were relieved,11(3-HSD1and GR protein expression on hippocampal is elevated. The middle dose and low dose of Zuo Gui Jiang Tang Jie Yu prescription had a weak effect.Conclusion:1. Combination the clinical features of diabetes mellitus with depression, Open-field experiment, Morris water maze test, blood glucose and glycosylated hemoglobin, insulin resistance, lipids indicators can create an evaluation system of diabetes mellitus with depression animal models.2.The method of14days high fat diet, low dose STZ (38mg/kg) injection and28days of chronic stress can be successfully prepared animal models of diabetes mellitus with depression.3.The hypothalamus, pituitary, adrenal of diabetes mellitus with depression rats were serious injury. The HPA axis hypersecretion exacerbated, and the content of corticosterone abnormally elevated lead to hippocampus pathological changes. The up regulation of11β-HSD1and the down regulation of GR expression in hippocampal is likely to participate in the damage of hippocampus, and to promote the development of diabetes mellitus with depression.4. The Zuo Gui Jiang Tang Jie Yu prescription can adjust weight and behavior of the model rat, improve blood glucose, blood lipids, insulin resistance, HPA axis hyperactivity, reduce hippocampal damage. Its therapeutic effect may be associated with the increased GR expression and reduce11β-HSD1expression in hippocampal. The treatment of Zuo Gui Jiang Tang Jie Yu prescription for diabetes mellitus with depression to be worthy of further research and development.