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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 investigate the effect of single administration of Dendrobium Compound on insulin signaling in db / db mice and to explore the related mechanism. Methods: Thirty male db / db mice aged 14-16 weeks were randomly divided into model group, Chinese medicine group 1 and Chinese herb group 2 according to fasting blood glucose and body weight. The other 10 db / m mice were normal group. After a single dose of Dendrobium Compound 1 and 2, the changes of glucose tolerance (OGTT) were observed from the overall level. After a single administration of 30 and 60 min, the level of 6-phosphofructokinase- 1 (PFK) and pyruvate dehydrogenase (PDH) activity, insulin receptor (InsR) and Akt protein phosphorylation levels. Results: Compared with the normal group, the blood glucose levels of OGTT at 0, 30, 60 and 120 min in model group were significantly increased, and the activities of PFK and PDH in hepatocytes were significantly decreased. The expressions of InsR and Akt at 30 min and 60 min were significantly decreased P <0.01). Compared with the model group, single dose of Dendrobium Mixture 1 and 2 could obviously reduce the blood glucose level of OGTT 60 and 120 min in db / db mice (P <0.05, P <0.01), and improve the glucose tolerance; Dendrobium Prescriptions 1 and 2 both increased the activities of PFK and PDH in hepatocytes and promoted the phosphorylation of Insr Tyr1150 / 1151, Akt Thr308 and Ser473, which showed the time-dependent effect on drugs (P <0.05, P <0.01). Conclusion: The single dose of Dendrobium Compound 1 and 2 can increase the glucose tolerance and increase the activity of PFK and PDH in db / db mice, which may be related to the increase of InsR Tyr150 / 1151, Akt Thr308 and Ser473 Phosphorylation, improve the rapid transduction of insulin signaling.