1，25-二羟维生素D_3对链脲菌素诱导的小鼠1型糖尿病预防作用及机制探讨

The Prevention and Mechanism of 1,25-dihydroxyvitamin D_3 to Type 1 Diabetes Induced by Streptozotocin in KM Mice through Regulating Bax and Bcl-xL Protein Expression

目的1,25-二羟维生素D_3[1,25-(OH)_2D_3]对连续多次小剂量链脲菌素(the multiple low dose streptozotocm,MLDS)诱导的1型糖尿病小鼠的预防作用及其机制初探。方法MLDS腹腔注射制备1型糖尿病小鼠模型,以血糖水平持续高于16.7mmol/L为成模标准。实验共分三组,分别为正常对照组、糖尿病组、预防组。采用便携式血糖仪监测各组血糖水平;放射免疫法检测各组血清胰岛素含量;免疫组化法检测各组胰岛细胞凋亡相关蛋白Bax和Bcl-xL表达。结果MLDS诱发的1型糖尿病模型在第四周基本建成。MLDS使小鼠血糖升高,血清胰岛素含量下降,Bax上调、Bcl-xL下调。预防组血糖水平下降,血清胰岛素升高,Bax下调、Bcl-xL上调,糖尿病发病率下降,与糖尿病组比较有显著差异(P<0.05)。结论1,25-(OH)_2D_3可有效预防MLDS诱导的1型糖尿病的发生,其效应可能与1,25-(OH)_2D_3调节Bax和Bcl-xL蛋白表达平衡有关。

Objective To investigate the prevention and the mechanism of 1, 25 - dihydroxyvitamin I）3 to type 1 diabetes by streptozotocin- induced in KM mice. Methods Experimental type 1 diabetes mice model with the blood glucose level which was consistently higher than 16.7mmol/L were produced by intraperitoneal injection of MLDS. There are three groups in this studay, which were normal control group, diabetes group, and 1, 25 - dihydroxyvitamin I）3 prevention group. Blood glucose level was monitored using a one - touch blood glucose meter. Radioimmunnity analysis was used to detect the serum insulin level. The protein expression level of bax and bcl - xL in islets were detected with technique. Results MLDS- induced type 1 diabetes mice model was finished in the fourth week. Blood glucose level and bax protein expression level increased after the treatment of MLDS, but serum insulin level and bcl- xL protein expression level decreased. 1, 25 - dihydroxyvitamin D3 prevented diabetes induced by MLDS in KM mice. The blood glucose level decreased, the serum insulin level increased. Bcl - xL protein expression was up regulated, bax protein expression was down regulated and the incidence of diabetes decreased significantly in 1, 25 - dihydroxyvitamin D3 prevention group compared with the control. Conclusion 1, 25 - dihydroxyvitamin D3 treatment could prevent type 1 diabetes through regulating the protein expression of bax and bel - xL.