复方石斛合剂单次给药对db/db小鼠胰岛素信号的影响

Effect of Compound Shihu Mixture Single-Dose Administration on Insulin Signaling in db / db Mice

目的:探讨复方石斛合剂单次给药对db/db小鼠胰岛素信号的影响,并探讨相关的作用机制。方法:选取30只14~16周龄雄性db/db小鼠,按空腹血糖及体重随机分成模型组、中药1方组、中药2方组;另10只db/m小鼠为正常组。以复方石斛合剂1方与2方单次给药后,从整体水平观察葡萄糖耐量(OGTT)的变化;单次给药30 min与60 min后,从细胞水平观察肝细胞6-磷酸果糖激酶-1(PFK)与丙酮酸脱氢酶(PDH)活性,胰岛素受体(InsR)与Akt蛋白磷酸化水平的变化。结果:与正常组比较,模型组db/db小鼠OGTT 0,30,60,120 min的血糖水平显著升高,肝细胞PFK与PDH活性显著降低,30 min与60 min InsR与Akt蛋白表达显著降低(P<0.01);与模型组比较,石斛合剂1方和2方单次给药均能明显降低db/db小鼠OGTT 60,120 min的血糖水平(P<0.05,P<0.01),改善葡萄糖耐量;石斛合剂1方和2方单次给药均增加肝细胞PFK与PDH活性,促进InsR Tyr1150/1151与Akt Thr308和Ser473磷酸化水平,呈现药物时间依赖效应(P<0.05,P<0.01)。结论:复方石斛合剂1方,2方分别单次给药都能提高db/db小鼠的葡萄糖耐量,增加肝细胞PFK和PDH酶活性,其机制可能与增加InsR Tyr150/1151与Akt Thr308和Ser473磷酸化,改善胰岛素信号的快速转导有关。

Objective： To study the effect of compound Shihu mixture （CSM） single-dose administration on insulin signaling in db/db mice. Method： According of the fasting blood glucose and body weight, 30 male db/db mice of 14-16 weeks were randomly divided into model group, Chinese medicine group 1 and Chinese medicine group 2; another 10 db/m mice were selected as normal group. After single-dose administration of CSM1 and CSM2, glucose tolerance （OGTT） levels were determined from the overall aspect. The changes in levels of 6-phosphofructokinase-1 （PFK） , pyruvate dehydrogenase （PDH） , and expression levels of insulin receptor （InsR） and Akt phosphorylation were determined at 30 min and 60 min of administration. Result ： As compared with the normal group, the blood glucose OGTT levels were significantly increased in model group at 0, 30, 60, 120 min; activities of PFK and PDH in hepatic cells were significantly decreased; the protein expression levels of InsR and Akt were significantly reduced at 30 min and 60 min （P 〈 0.01 ）. As compared with the model group, the single-dose administration of both CSM1 and CSM2 could significantly reduce blood glucose OGTT levels at 60, 120 min （P 〈 0.05, P 〈 0.01 ） ; increase the activities of PFK and PDH in hepatic cells, and promote the phosphorylation levels of InsR Tyrll50/ll51, Akt Ser473 and Thr308 in a time-dependent manner （P 〈0.05, P 〈 0.01 ）. Conclusion： Single-dose administration of both CSM1 and CSM2 could improve the glucose tolerance in db/db mice and increase the activities of PFK and PDH in hepatic cells. The mechanism may be associated with improving insulin signal transduction and promoting the phosphorylation of InsR Tyr150/1151, Akt Serg73 and Thr308.