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目的:观察黄连温胆汤对糖尿病大鼠海马胰岛素抵抗和神经发生的作用。方法:通过高糖高脂饲料喂养50 d合并1次性35 mg·kg-1链脲佐菌素(STZ)腹腔注射造成糖尿病大鼠模型。通过测定血糖,选取模型成功大鼠,随机分为空白,模型,二甲双胍(0.2 g·kg-1),小檗碱(0.2 g·kg-1),黄连温胆汤3,6,12 g·kg-17组,按相应剂量灌胃给药30 d。测定大鼠口服葡萄糖耐量(OGGT),海马胰岛素(Ins)含量,胰岛素受体(InsR)和β-分泌酶(BACE1)mRNA表达,苏木精-伊红(HE)染色观察海马齿状回(DG)区神经元细胞数目和变化。结果:给予50 d高脂饲料和35 mg·kg-1STZ后,糖尿病模型组与空白组大数相比,出现明显的OGGT受损(P<0.01),海马InsR mRNA表达升高(P<0.01),BACE1表达降低(P<0.05),DG区神经元数目减少,细胞排列疏松;而给予二甲双胍(0.2 g·kg-1)组,小檗碱(0.2 g·kg-1)和黄连温胆汤3,6,12 g·kg-1组的大鼠可以逆转这些现象(P<0.05,P<0.01)。结论:黄连温胆汤能明显改善糖尿病大鼠受损的OGGT,抑制海马BACE1表达,改善DG区神经元受损,其作用机制可能与增加海马InsR表达有关。
Objective: To observe the effect of huanglian wendan decoction on hippocampal insulin resistance and neurogenesis in diabetic rats. Methods: Diabetic rats were induced by intraperitoneal injection of high-sucrose and high-fat diet for 50 days and intraperitoneal injection of 35 mg · kg-1 streptozotocin (STZ) once a day. The rats were randomly divided into blank, model, metformin (0.2 g · kg -1), berberine (0.2 g · kg -1), Huanglian Wendan Decoction 3,6,12 g · kg-17 group, according to the corresponding dose of oral administration of 30 d. The levels of OGGT, Ins, and BACE1 mRNA in rat hippocampus were detected by HE staining. The changes of OGGT, Ins, DG) neurons in the number and changes. Results: After 50 days of high-fat diet and 35 mg · kg-1 STZ, the expression of InsR mRNA in hippocampus was significantly increased in diabetic model group compared with the blank control group (P <0.01) ), BACE1 expression decreased (P <0.05), the number of neurons in DG decreased and the cells arranged in a loose manner. However, 0.2g · kg-1 metformin (0.2 g · kg-1) The rats in 3, 6 and 12 g · kg -1 groups could reverse these phenomena (P <0.05, P <0.01). Conclusion: Huanglian Wendan Decoction can significantly improve the damaged OGGT, inhibit the expression of BACE1 in hippocampus and improve the damage of neurons in DG area. Its mechanism may be related to increasing InsR expression in hippocampus.