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目的探讨生长抑素(SST)类似物奥曲肽对高脂饲料诱导的肥胖大鼠肝脏糖异生的影响。方法雄性SD大鼠随机分为正常对照组(n=16)和高脂饲料组(n=40),分别喂以普通饲料与高脂饲料。饲养24周后,从高脂饲料组中选出肥胖大鼠,分成肥胖组(n=16)和奥曲肽干预组(n=16)。奥曲肽干预组大鼠连续8 d皮下注射奥曲肽,剂量为每12 h 40 mg/kg BW。实验结束后测定大鼠的身长、体重、空腹血糖、血脂、血胰岛素及血浆生长抑素水平,计算Lee’s指数和HOMA指数。RTPCR测定葡萄糖-6-磷酸酶(G6pase)、磷酸烯醇式丙酮酸羧激酶(Pepck)和叉头框家族转录因子1(Foxo1)mRNA表达水平。蛋白质免疫印迹法测定Foxo1在核蛋白和胞浆蛋白中的表达。结果肥胖组大鼠体重、空腹血糖、血脂、血胰岛素水平及HOMA指数较正常对照组大鼠显著升高;与肥胖组大鼠比较,奥曲肽干预组大鼠上述指标均下降。肥胖组大鼠血浆SST水平较正常对照组大鼠有降低的趋势(P>0.05),奥曲肽干预组大鼠血浆SST水平较肥胖组大鼠显著升高(P<0.05)。肥胖组大鼠肝脏G6pase、Pepck及Foxo1 mRNA表达水平及肝细胞核内与胞浆中Foxo1蛋白表达水平的比值较正常对照组均显著增加(P<0.01),而奥曲肽干预组大鼠则较肥胖组大鼠显著下降(P<0.01)。结论奥曲肽可改善高脂饲料诱导的肥胖大鼠异常增强的肝脏糖异生作用,其作用机制可能与降低Foxo1的活性和表达,抑制肝脏G6pase及Pepck的转录有关。
Objective To investigate the effect of octreotide, an analog of somatostatin (SST), on gluconeogenesis in the liver of obese rats induced by high fat diet. Methods Male Sprague-Dawley rats were randomly divided into normal control group (n = 16) and high-fat diet group (n = 40), fed with normal diet and high-fat diet respectively. After feeding for 24 weeks, the obese rats were divided into the obesity group (n = 16) and octreotide intervention group (n = 16) from the high fat diet group. Octreotide intervention group octreotide subcutaneous injection of 8 consecutive days, the dose of 40 mg / kg BW every 12 h. After the experiment, the body length, body weight, fasting blood glucose, blood lipids, blood insulin and plasma somatostatin levels were measured to calculate Lee’s index and HOMA index. RTPCR was used to determine the mRNA expression levels of glucose-6-phosphatase (G6pase), phosphoenolpyruvate carboxykinase (Pepck) and forkhead box family transcription factor 1 (Foxo1). Western blotting was used to detect the expression of Foxo1 in nucleoprotein and cytoplasmic protein. Results The body weight, fasting blood glucose, blood lipid, insulin level and HOMA index in obese group were significantly higher than those in normal control group. Compared with obese group, the above indexes of octreotide intervention group decreased. Plasma SST levels in obese rats were lower than those in normal rats (P> 0.05). Plasma SST levels in obese rats were significantly higher than those in obese rats (P <0.05). The ratio of liver G6pase, Pepck and Foxo1 mRNA in the obesity group and the ratio of Foxo1 protein in the nucleus and cytoplasm were significantly increased (P <0.01), while those in the octreotide intervention group were higher than those in the obese group Rats decreased significantly (P <0.01). Conclusion Octreotide can improve the abnormally enhanced hepatic gluconeogenesis in obese rats induced by high-fat diet. The mechanism may be related to the decrease of Foxo1 activity and expression, and the inhibition of liver G6pase and Pepck transcription.