Genipin对糖尿病小鼠下丘脑细胞凋亡指数及解偶联蛋白2表达的影响

Effects of genipin on apoptosis index and expression of uncoupling protein 2 at hypothalamus in diabetic mice

目的探讨genipin对糖尿病小鼠下丘脑细胞凋亡指数(AI)及解偶联蛋白2(UCP2)表达的影响。方法 48只健康雄性小鼠随机分为正常对照组、糖尿病模型组和genipin低、高剂量干预组,每组12只小鼠。采用长期高脂饮食及链脲佐菌素胰岛破坏法建立2型糖尿病小鼠模型。Genipin低、高剂量干预组小鼠分别给予5 mg/(kg.d)、10 mg/(kg.d)的genipin 0.1 ml连续灌胃2周,正常对照组和糖尿病模型组用等量生理盐水替代。分别采用TUNEL染色法和免疫组化染色检测并计算各组小鼠下丘脑AI和UCP2蛋白阳性细胞率;采用实时PCR和Western Blot法检测下丘脑UCP2 mRNA和蛋白的表达水平。结果糖尿病模型组、genipin低剂量和高剂量干预组下丘脑AI明显高于正常对照组(均P<0.05);而genipin低剂量和高剂量干预组下丘脑AI明显低于糖尿病模型组(均P<0.05);且genipin低剂量干预组和genipin高剂量干预组间差异无统计学意义。糖尿病模型组UCP2蛋白阳性细胞率明显高于正常对照组(P<0.05),而genipin低剂量和高剂量干预组UCP2蛋白阳性细胞率均明显低于糖尿病模型组(均P<0.05)。Genipin低剂量和高剂量干预组UCP2 mRNA和蛋白的表达水平均明显低于糖尿病模型组(均P<0.05)。与genipin低剂量干预组比较,geni-pin高剂量干预组UCP2蛋白阳性细胞率、UCP2 mRNA和蛋白的表达水平明显降低(均P<0.05)。结论 Ge-nipin可以减少糖尿病小鼠下丘脑细胞凋亡和UCP2的表达。

Objective To investigate the effects of genipin on apoptosis index（AI） and expression of uncoupling protein 2（UCP2） at hypothalamus in diabetic mice.Methods Forty-eight healthy male mice were randomly divided into normal control group,diabetic model group,low-dose genipin intervention group and high-dose genipin intervention group,with each group 12 mice.Mice model of type 2 diabete mellitus were developed by long-term high fat diet and STZ insulin damage method.The low-dose genipin intervention group and high-dose genipin intervention group were given 5 mg/（kg·d） or 10 mg/（kg·d） genipin 0.1 ml by gavage for 2 weeks,separately.The normal control group and diabetic model group were given equivalent normal saline by gavage instead.The AI and the rate of UCP2 protein positive cell at hypothalamus in all the groups were detected by TUNEL staining and immunohistochemistry method,separately.The expression of UCP2 mRNA and protein were detected by Real-time PCR and Western Blot method.Results The AI at hypothalamus in diabetic model group,low-dose and high-dose genipin intervention groups were significantly higher than that in normal control group（all P0.05）;while the AI in low-dose and high-dose genipin intervention groups were significantly lower than that in diabetic model group（all P0.05）.There was no significant difference of AI between low-dose and high-dose genipin intervention groups.The rate of UCP2 protein positive cell in diabetic model group was significantly higher than that in normal control group（P0.05）;while the rate of UCP2 protein positive cell in low-dose and high-dose genipin intervention groups were significantly lower than that in diabetic model group（all P0.05）.The expression of UCP2 mRNA and protein in low-dose and high-dose genipin intervention groups were significantly lower than that in diabetic model group（all P0.05）.Compared with low-dose genipin intervention group,the rate of UCP2 protein positive cell and the expression of UCP2 mRNA and protein in high-dose genipin intervention group were significantly decreased（all P0.05）.Conclusion Genipin can reduce the apoptosis and the expression of UCP2 at hypothalamus in diabetic mice.