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【目的】观察比较慢性心理应激对2型糖尿病(T2DM)小鼠胰岛及肝细胞糖皮质激素受体(GR)表达的影响及加减逍遥散的干预作用。【方法】以自发性糖尿病(KK)小鼠为研究对象,采用高糖高脂饲料喂养8周复制T2DM小鼠模型。采用电击、夹尾、禁食、禁水、合笼饲养等应激刺激复制慢性心理应激模型。102只小鼠随机分为空白对照组、应激对照组、逍遥散组、应激加逍遥散低剂量组及应激加逍遥散高剂量组5组。采用酶联免疫吸附(ELISA)法检测糖化血红蛋白(HbA1c),免疫荧光法检测GR的表达。【结果】与空白对照组比较,应激对照组小鼠HbA1c值显著升高(P<0.01),胰岛细胞内GR表达差异无统计学意义,肝细胞内GR表达显著下降(P<0.01);逍遥散组小鼠HbA1c值显著降低(P<0.01),胰岛细胞与肝细胞内GR表达均显著下降(P<0.01)。与应激对照组比较,应激加逍遥散低剂量组小鼠HbA1c值显著降低(P<0.01),胰岛细胞GR表达显著下调(P<0.01),而肝细胞内GR表达差异无统计学意义;应激加逍遥散高剂量组小鼠HbA1c值显著降低(P<0.01),胰岛细胞内GR表达显著下调(P<0.01),而肝细胞内GR表达则显著上调(P<0.01)。【结论】加减逍遥散能够降低T2DM小鼠的HbA1c水平,并且对抗慢性心理应激对T2DM小鼠HbA1c的影响,其作用机制可能与加减逍遥散调节T2DM小鼠胰岛与肝细胞内GR的表达有关。
【Aim】 To observe the effect of chronic psychological stress on glucocorticoid receptor (GR) expression in pancreatic islets and hepatocytes of type 2 diabetes mellitus (T2DM) mice and the intervention effect of Xiaoyao San. 【Methods】 In spontaneous diabetic (KK) mice, T2DM mice were fed with high glucose and high fat diet for 8 weeks. Chronic psychological stress model was replicated by stress stimulation such as electric shock, tail clipping, fasting, water forbidding and caged feeding. 102 mice were randomly divided into blank control group, stress control group, Xiaoyao powder group, stress plus Xiaoyaosan low dose group and stress plus Xiaoyaosan high dose group. Glycated hemoglobin (HbA1c) was detected by enzyme-linked immunosorbent assay (ELISA), and the expression of GR was detected by immunofluorescence. 【Results】 Compared with the blank control group, the HbA1c level in the stress control group was significantly increased (P <0.01), and there was no significant difference in the expression of GR in islet cells (P <0.01). Xiaoyaosan group had significantly lower HbA1c (P <0.01), while GR expression in islet cells and hepatocytes decreased significantly (P <0.01). Compared with the stress control group, the HbA1c level was significantly decreased (P <0.01) and the expression of GR in pancreatic islet cells was significantly decreased (P <0.01), while the expression of GR in hepatocytes was not significantly different (P <0.01). The GR expression in islet cells was significantly down-regulated (P <0.01), while the expression of GR in hepatocytes increased significantly (P <0.01). 【Conclusion】 Xiaoyaoyaosan can reduce the level of HbA1c in T2DM mice and antagonize the effects of chronic psychological stress on HbA1c in T2DM mice. The mechanism may be related to the effect of Xiaoyaoyaosan on the islet and hepatic GR in T2DM mice Expression related.