洋参御糖丸调控糖尿病大鼠肝脏胰岛素PI3K信号通路的机制研究

Yangshen Yutang Pellet's Adjustment Mechanism for the P13K Signal Pathwayof Insulin in Rats with Diabetes

目的:观察洋参御糖丸对DM大鼠肝脏胰岛素PI3K信号通路的调节作用。方法:4周龄Wistar大鼠50只,选取10只作为空白组,给予普通饲料,其余40只给予高脂高糖饲料,喂养8周,腹腔注射STZ,做成糖尿病大鼠模型,分为模型组、二甲双胍组、洋参御糖方高剂量组、洋参御糖方低剂量组,每组10只。各组给予相应药物灌胃,每日一次,给药剂量:洋参御糖丸低剂量组1.35 g·(kg·d)-1,高剂量组2.7 g·(kg·d)-1,二甲双胍组70 mg·(kg·d)-1。模型组和空白组给予等体积蒸馏水灌胃。各组继续给予高糖高脂饲料,药物干预4周末,进行肝脏取材。血糖仪测定各组大鼠尾静脉空腹血糖;放免法测定空腹血清胰岛素;氧化酶法测定肝糖原含量;结果:①模型组大鼠血糖、血清胰岛素与空白组比较明显增高(P<0.05);洋参御糖丸高、低剂量组及二甲双胍组血糖及血清胰岛素较模型组不同程度降低,(P<0.05);二甲双胍组上述指标降低程度优于洋参御糖丸高、低剂量组(P<0.05);②模型组大鼠肝糖原含量较空白组明显降低(P<0.05);洋参御糖丸高剂量组和二甲双胍组肝糖原含量较模型组显著升高,(P<0.05);洋参御糖丸低剂量组肝糖原含量与模型组比较差异无统计学意义(P>0.05);③模型组大鼠肝脏IRS-1、GLUT-4和PI3K-p85蛋白表达与空白组相比显著降低(P<0.05);洋参御糖丸高剂量组及双胍组IRS-1、GLUT-4和PI3K-p85蛋白表达与模型组比较显著提高(P<0.05);而洋参御糖丸低剂量组与模型组相比上述指标无明显差异(P>0.05)。结论:洋参御糖丸可能通过增加DM大鼠肝脏IRS-2、GLUT-4和PI3K-p85蛋白表达,增强胰岛素PI3K信号转导,抑制肝糖输出,发挥降糖和改善IR作用。

Objective ：To observe the adjustment of Yangshen Yutang Pellet for the P13 K signal pathway of insulin in DM Rats with diabetes. Methods： 10 of the 50 Wistar rats of 4 -month -old were chosen randomly as the blank group（ 10 rats） which were giv- en common feed and the other 40 rats were given high - fat and high - suger feed. The feed lasted for 8 weeks and then intraper- itoneal injection of STZ was performed to establish the diabetes rats models. The models were divided into the model group, mel- bine group, Yangshen Yutang Fang group of high dosage and Yangshen Yutang Fang group of low dosage, 10 rats in each group. Each group was intragastrieally administrated with corresponding drugs per time one day. The dosages ： 1.35 g/kg d for the Yan- gshen Yutang Fang group of low dosage ,2.7 g/kg d for the Yangshen Yutang Fang group of high dosage,70 mg/kg d for the melbine group. The model group and the blank group were intragastrically administrated with distilled water of same volume. Each group was continually being fed with high - suger and high - fat food. After 4 weeks for drugs intervention, the study objects were taken out of the livers. The fasting blood - glucose of caudal vein was detected by glueometer. The fasting serum insulin was detec- ted by radioimmunoassay. The content of hepatic glycogen was detected by gucose oxidase method. Results ： 1 ） The levels of blood sugar and serum insulin in the model group were obviously improved as compared with the blank group（ P 〈 0.05 ） ;the levels of blood sugar and serum insulin in the melbine group, Yangshen Yutang Fang group of high dosage and Yangshen Yutang Fang group of low dosage declined to different degree when compared those in the model group（ P 〈 0.05 ） ;the decline of the above in- dicators in the rnelbine group was superior to that of the Yangshen Yutang Fang group of low and high dosage（ P 〈 0.05 ） ;2） The content of hepatic; glycogen in the model group greatly declined when compared with the blank group（ P 〈 0.05 ） ;the content of hepatic glycogen in the Yangshen Yutang Fang group of high dosage and the melbine group greatly increased when compared with that in the model group（ P 〈 0.05 ） ;the difference of the contents of hepatic glycogen in the Yangshen Yutang Fang group of low dosage and the model group didn＇t have statistical significance（ P 〉 0.05 ） ;3 ） The protein expression of I RS - 1, GLUT-4 and PI3K -p85 in model group remarkably declined when compared with the blank group（ P 〈 O. 05 ） ;the protein expression of IRS - 1 ,GLUT-4 and PI3K - p85 in the Yangshen Yutang Fang group of high dosage and the melbine group remarkably increased when compared with the model group（P 〈0.05 ） while the difference of the above indicators between the Yangshen Yutang Fang group of low dosage and the control group had no statistical difference（ P 〉 0.05 ）. Conclusion：By increasing the protein expres- sion of IRS - 1, GLUT -4 and PI3 K - p85 of the DM rats＇ livers, Yangshen Yutang Pellet can improve the signal transduction in- sulin PI3K and inhibit the hepatic glucose output to lower sugar and improve IR.