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 C56 BL/6 J mice,then the glucose related indexes,micro RNA-370 levels in the serum and liver tissue and the expression of gluconeogenesis key protein( G6 Pase and PEPCK) in the liver tissue to observe the treatment effects of salidroside on type 2 diabetic-caused gluose metabolic disorder. In cell test,we isolated primary hepatocytes,then silenced or over-expressed 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 G6 Pase 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 G6 Pase( P<0.05),micro RNA-370 mimic alone group can significantly increase the protein expression level of PEPCK and G6 Pase( P < 0.05),compared with the micro RNA-370 mimic 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.
出处
《医药导报》
CAS
北大核心
2018年第3期279-284,共6页
Herald of Medicine
基金
吉林省食品药品安全监测中心项目[(2014)科技字(3309)号]
