丹参酮Ⅰ对2型糖尿病ICR小鼠抗糖作用的研究

Anti-diabetic effect of tanshinone Ⅰ on ICR mice with type 2 diabetes mellitus

目的观察丹参酮Ι对高脂高糖饮食结合多次小剂量链脲佐菌素(STZ)注射诱导的2型糖尿病(T2DM)模型ICR小鼠肝脏的影响并分析其可能的作用机制。方法制备小鼠T2DM模型,随机分为模型组、丹参酮Ι(高剂量、中剂量、低剂量)组、二甲双胍(Met)组和吡格列酮(Pio)组,随后这6组继续给于高脂高糖饲料喂养3周,每天注射相应浓度的药物,同时,对7组(包括正常组)小鼠每周测一次空腹血糖和体重。3周末,取小鼠肝脏,运用HE染色观察各组的病理变化,免疫组化法和Western blot法检测各组蛋白酪氨酸磷酸酶1B(PTP1B)、蛋白激酶B(Akt)、P-Akt蛋白表达水平。结果丹参酮Ι高剂量组可以降低T2DM ICR小鼠的血糖(P<0.05),增加其体重(P<0.05)。丹参酮Ι3个剂量组肝组织中未见明显细胞质肿胀和细胞核固缩现象,且组织中炎症较轻。免疫组化法结果显示,丹参酮Ι高剂量组可以降低T2DM ICR小鼠肝脏组织中PTP1B蛋白的表达(P<0.05)。Western blot法显示,丹参酮Ι中剂量组和高剂量组可以降低T2DM ICR小鼠肝脏组织中PTP1B蛋白的表达(P<0.05),各组中Akt的表达均无明显差异,丹参酮Ι高剂量组可以提高T2DM小鼠肝脏中P-Akt的蛋白表达(P<0.05)。结论高剂量的丹参酮Ι可以降低STZ诱导的T2DM小鼠的空腹血糖水平和肝损伤,同时降低肝脏PTP1B的表达,提高肝脏P-Akt的表达。

Objective To observe the effect of tanshinone Ⅰ on the liver of ICR mice with type 2 diabetes mellitus（ T2DM）,induced by high-fat diet combined with several low-dose streptozotocin（ STZ） injections and to explore its potential mechanism. Methods Establish the mouse model of T2 DM and mice would be divided randomly into the model group,high-dose tanshinone Ⅰ group,medial-dose tanshinone Ⅰ group,low-dose tanshinone Ⅰ group,the metformin（ Met） group and the pioglitazone（ Pio） group. The groups above were fed with high-fat diet and received daily injections of various-dose drugs as previously described for a period of three weeks. Livers were extracted at the end of the third week. Pathological changes by means of hematoxylin and eosin（ HE） staining were observed. The protein expression levels of protein tyrosine phosphatase-1B（ PTP1B）,Akt and P-Akt were detected by the immunohistochemical experiment and Western blot. Results High-dose tanshinone Ⅰ could decrease FBG of mice with type 2 diabetes mellitus（ P〈 0. 05） and increase their body weight（ P〈 0. 05）. Cells with cytoplasm tumefied and nucleus pyknosed,necrocytosis and inflammation in tanshinone Ⅰ groups could be seen less compared to the modle group. Immunohistochemistry showed that high-dose tanshinone Ⅰ could decrease the protein expression of PTP1 B in mice with type 2 diabetes mellitus（ P 〈0. 05）. Analysis of Western blot revealed that medial-dose and high-dose tanshinone Ⅰ could decrease the protein expression levels of PTP1 B in mice with T2DM（ P 〈0. 05）. At the same time,there was no significant difference in the protein expression levels of Akt between the model group and tanshinone Ⅰ groups. High-dose tanshinone Ⅰ could increase the protein expression levels of PAkt compared to the modle group（ P〈 0. 05）. Conclusion Tanshinone Ⅰ in high concentration could decrease FBG and relieve the injury of liver in T2 DM ICR mice,induced by high-fat diet combined with several low-dose STZ injections. At the same time,it could also decrease their protein expression levels of PTP1 B and increase PAkt expressions.