红景天苷通过micro RNA-370改善2型糖尿病小鼠糖代谢的作用机制

摘要

目的 观察红景天苷改善2型糖尿病小鼠血糖作用,探讨红景天苷改善2型糖尿病小鼠糖代谢紊乱的分子机制.方法 采用高脂饮食联合腹腔注射链脲佐菌素(STZ)建立2型糖尿病小鼠模型,检测血糖相关指标、血清和肝脏micro RNA-370表达,以及肝组织糖异生关键酶(PEPCK/G6Pase)蛋白表达水平,观察红景天苷对2型糖尿病小鼠糖代谢紊乱的改善作用.分离培养小鼠原代肝细胞,采用瞬时转染技术将micro RNA-370沉默或过表达,观察micro RNA-370对糖代谢的影响及红景天苷调节糖代谢的分子机制.结果 与模型对照组比较,红景天苷各剂量组小鼠血糖相关指标均明显改善(P<0.05);血清和肝组织micro RNA-370表达水平以及肝组织PEPCK/G6Pase蛋白相对表达水平均不同程度降低,且呈剂量依赖性,中、大剂量组降低较明显(P<0.05),小剂量组有降低趋势,但差异无统计学意义.细胞实验中,与空白对照组比较,红景天苷组和micro RNA抑制剂组PEPCK/G6Pase表达均被抑制(P<0.05),micro RNA-370激动剂组PEPCK/G6Pase表达明显促进(P<0.05),红景天苷与micro RNA-370激动剂联用能逆转micro RNA-370激动剂所致PEPCK/G6Pase蛋白表达增高(P<0.05).结论 红景天苷能明显改善2型糖尿病小鼠糖代谢紊乱,且该作用至少部分通过抑制micro RNA-370实现.%Objective To observe the effects of salidroside regulating glucose metabolism in type 2 diabetic mice,then to explore the molecular mechanism. Methods Type 2 diabetes model was induced by feeding high-fat diet and intraperitoneal injecting STZ to male C56BL/6J mice,then the glucose related indexes,micro RNA-370 levels in the serum and liver tissue and the expression of gluconeogenesis key protein(G6Pase and PEPCK) in the liver tissue to observe the treatment effects of salidro-side on type 2 diabetic-caused gluose metabolic disorder.In cell test,we isolated primary hepatocytes,then silenced or over-ex-pressed micro RNA-370 in mouse primary hepatocytes to observe the molecular mechanism of glucose metabolic regulation of the micro RNA-370 and salidroside. Results Treated with salidroside 40,80 and 160 mg·kg-1,the results showed that compared with the model control group,the glucose related indexes were all improved significantly.The relative expression levels of micro RNA-370 in serum and liver,and that of PEPCK and G6Pase all reduced in different degrees,dose-dependently.The changes of middle and high dose group decreased significantly(P<0.05),that of low dose group had a decreasing trend but no statistically significant.In the cell test,compared with the normal control group,salidroside alone group and micro RNA-370 inhibitor group were able to reduce the protein expression level of PEPCK and G6Pase(P<0.05),micro RNA-370mimic alone group can signifi-cantly increase the protein expression level of PEPCK and G6Pase(P<0.05),compared with the micro RNA-370mimic alone group,combining micro RNA-370 mimic and salidroside can significantly reverse the increasing caused by micro RNA-370 mimic alone(P<0.05). Conclusion Our research found that salidroside can improve glucose metabolism disorder in type 2 diabetic mice,and at least in part,through the suppression of micro RNA-370 expression for the first time.