铬对糖尿病大鼠骨骼肌组织基因表达的调控作用

目的　研究铬对糖尿病大鼠代谢相关基因表达的调控作用。方法　雄性Wistar大鼠随机分成 3组 :正常对照组、糖尿病对照组、糖尿病补铬组。糖尿病补铬组每日以 2 0 0 μg kgbw的铬连续灌胃 6 0天。采用mRNA差异显示技术、基因片段的克隆、测序、同源性分析等观察各组大鼠之间骨骼肌中基因表达的变化。结果　分离到糖尿病补铬组与糖尿病对照组之间出现明显差异的 4 0 0bp以上的cDNA片段 11条 ,其中在糖尿病补铬组中高表达的cDNA片段 4条 ;在糖尿病对照组中高表达的cDNA片段 7条。同源性比较结果显示Cr 3与GLUT4 (葡萄糖转运体 4 )的同源性为 98% ;Cr 5与IRS 1(胰岛素受体底物 1)的同源性为 10 0 % ,RT PCR验证结果显示GLUT4表达量在糖尿病补铬组高于糖尿病对照组。结论　铬可诱导糖尿病大鼠骨骼肌中GLUT4mRMA的表达 ,这可能是铬改善糖尿病糖、脂代谢紊乱的分子机制之一。

Regulation of chromium on gene expression of skeletal muscles in diabetic rats

OBJECTIVE: To study the regulation of chromium on gene expression related to metabolism of skeletal muscles in diabetic rats. METHODS: Male Wistar rats were assigned to three groups: normal control group (NC), alloxan-induced diabetic control group (DM), and DM with chromium supplementation group (DM + Cr). 200 microg Cr/kg bw perday was supplemented orally for 60 days. At the end of the treatment, the changes in gene expression among three groups were studied by mRNA differential display technique combined with cDNA fragments cloning, sequencing and BLASTn analysis. RESULTS: 11 cDNA fragments larger than 400bp expressed differences in skeletal muscles between DM + Cr group and DM group were isolated, 4 of them expressed higher in DM + Cr group, while the rest expressed higher in DM group. Cr-3 and GLUT4 are homologous with sequence identities of 98% and Cr-5 and IRS-1 are homologous with sequence identities of 100%. The expression level of GLUT4 mRNA in DM + Cr group are higher than those of DM group. CONCLUSION: Chromium supplementation could induce the expression of GLUT4 mRNA on skeletal muscles in diabetic rats. It may be one of the molecular mechanisms that chromium could improve the disorders of glucose and lipids metabolism in diabetic rats.