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大黄糖络丸对2型糖尿病大鼠肝损伤的影响及机制

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目的 探讨大黄糖络丸对2型糖尿病大鼠肝损伤的影响及机制.方法 将ZDF(fa/fa)大鼠给予高脂饲料诱导2型糖尿病模型,造模成功后随机分为模型组、阳性药对照组(0.18 g·kg-1二甲双胍)和低、中、高剂量实验组(0.54、1.08和2.16 g·kg-1大黄糖络丸),每组8只.选取8只ZDF(fa/+)大鼠作为对照组.对照组及模型组灌服等体积纯净水,每日1次,持续12周.给药结束后进行口服葡萄糖耐量试验(OGTT);检测大鼠空腹血糖水平、体质量及肝质量并计算肝指数;检测血清谷丙转氨酶(GPT)、谷草转氨酶(GOT)、三酰甘油(TG)、总胆固醇(TC)含量;用苏木精-伊红(HE)染色法和马松(Masson)染色法观察肝组织形态学变化.用蛋白质印迹检测肝组织磷酸化胰岛素受体底物1(p-IRS1)、磷酸化蛋白激酶B(p-Akt)及葡萄糖转运蛋白4(GLUT4)的蛋白表达.结果 对照组、模型组、阳性药对照组和高剂量实验组大鼠的空腹血糖分别为(4.71±0.45)、(29.90±2.97)、(15.28±4.52)和(13.84±1.55)mmol·L-1,肝指数分别为 2.31±0.46、4.03±0.18、3.37±0.23 和 3.38±0.24,p-IRS1 蛋白相对表达水平分别为 1.00±0.36、4.00±0.11、1.62±0.27 和 1.90±0.17,p-Akt蛋白相对表达水平分别为1.00±0.25、0.21±0.04、0.73±0.15和0.54±0.04,GLUT4 蛋白相对表达水平分别为 1.00±0.11、0.40±0.08、0.86±0.04和0.70±0.06.高剂量实验组上述指标与模型组比较,在统计学上差异均有统计学意义(P<0.01,P<0.05).结论 大黄糖络丸可有效改善2型糖尿病糖脂代谢和肝损伤,其作用机制可能与IRS1/Akt信号通路的激活有关.
Effects and mechanism of rhubarb Tangluo pill on liver injury in type 2 diabetic rats
Objective To investigate the effect and mechanism of rhubarb Tangluo pill on liver injury in type 2 diabetic rats.Methods ZDF(fa/fa)rats were given high-fat diet to induce type 2 diabetes model,and were randomly divided into model group,positive control group(0.18 g·kg-1 metformin)and experimental-L,-M,-H groups(0.54,1.08 and 2.16 g·kg-1 rhubarb Tangluo pill),with 8 rats in each group.Eight ZDF(fa/+)rats were selected as control group.The control group and model group were given equal volume of pure water once a day for 12 weeks.An oral glucose tolerance test(OGTT)was performed after administration.Fasting blood glucose level,body mass and liver mass of rats were measured and liver index was calculated.The contents of glutamic-pyruvic transaminase(GPT),glutamic oxalacetic transaminase(GOT),triglyceride(TG)and total cholesterol(TC)in serum were detected.The histomorphologic changes of liver were observed by hematoxylin-eosin(HE)staining and Masson staining.The protein expression of phosphorylated insulin receptor substrate 1(p-IRS1),phosphorylated protein kinase B(p-Akt)and glucose transporter 4(GLUT4)were detected by Western blotting.Results After administration,the fasting blood glucose levels of control group,model group,positive control group and experimental-H group were(4.71±0.45),(29.9±2.97),(15.28±4.52)and(13.84±1.55)mmol·L-1,respectively;the liver index were 2.31±0.46,4.03±0.18,3.37±0.23 and 3.38±0.24;the relative expression level of p-IRS1 protein were 1.00±0.36,4.00±0.11,1.62±0.27 and 1.90±0.17,respectively;the relative expression levels of p-Akt protein were 1.00±0.25,0.21±0.04,0.73±0.15 and 0.54±0.04,respectively;GLUT4 protein relative expression levels were 1.00±0.11,0.40±0.08,0.86±0.04 and 0.70±0.06,respectively.Compared with the model group,the above indexes in the experimental-H group were statistically significant(P<0.01,P<0.05).Conclusion Rhubarb Tanglu pill can effectively improve glycolipid metabolism and liver injury in type 2 diabetes mellitus,and its mechanism may be related to the activation of IRS1/Akt signaling pathway.

rhubarb Tangluo pillstype 2 diabetesliver injuryinsulin resistanceinsulin receptor substrate 1/protein kinase B signaling pathway

安冬、梁永林、高艳奎、闫丰喆、白敏、赵思晨、刘中唐、聂宵

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甘肃中医药大学基础医学院,甘肃兰州 730000

大黄糖络丸 2型糖尿病 肝损伤 胰岛素抵抗 胰岛素受体底物1/蛋白激酶B信号通路

甘肃省优秀博士生基金甘肃省高等学校产业支撑计划甘肃中医药大学研究生创新基金

23JRRA12182021CYZC-032022CX05

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(9)
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