奥曲肽对高脂饲料诱导的肥胖大鼠肝脏糖异生的影响  

Effects of octreotide on liver gluconeogenesis in obesity rats fed a high fat diet

作　　者：李茂[1] 刘瑞[1] 王小霞[1] 李献[1] 强鸥[1] 余涛[1] 唐承薇[1] 

机构地区：[1]四川大学华西医院生物治疗国家重点实验室人类疾病相关多肽研究室华西医院消化内科,成都610041

出　　处：《卫生研究》2015年第2期270-275,共6页Journal of Hygiene Research

基　　金：国家自然科学基金(No.30870919);四川省科技厅科技支撑计划(No.2010SZ0176)

摘　　要：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 verify the effects of octreotide on liver gluconeogenesis in high fat diet-induced obesity rat. Methods Male SD rats were randomly assigned to control（ n = 16） and high-fat diet group（ n = 40）. After 24 weeks,obese rats selected from high-fat diet group were placed into obese group（ n = 16） and octretide-treated group（ n = 16）. Rats in the octreotide-treated group were subcutaneously injected with octreotide per 12 h（ 40 mg / kg body weight） for 8 days. Body lengths,body weight,fastingplasma glucose（ FPG）,triglyceride（ TG）,total cholesterol（ TC）,fasting serum insulin and plasma somatostatin（ SST） levels were measured. The Lee＇s index and HOMA index were calculated. Expression of glucose-6-phosphatase（ G6pase）,phosphoenolpyruvate carboxykinase（ Pepck） and forkhead box-containing protein O subfamily-1（ Foxo1）mRNA were measured by RT-PCR. Foxo1 protein in nuclear and cytoplasm were quantified by western blotting. Results Compared with control group,body weight,FPG,TG,TC,insulin and HOMA index in obese group were significantly increased. Octreotide treatment showed obviously reduced levels of the parameters. The plasma SST levels in the obese group tended to decrease compared with that in the control group（ P 〉0. 05）,while plasma SST levels was increased in the octreotide-treated group compared with that in the obese group（ P〈 0. 05）. Obese rats display more G6 pase,Pepck and Foxo1 mRNA and higher ratio of nuclear Foxo1 protein to cytoplasm Foxo1 protein than control rats（ P 〈0. 01）,whereas octreotide intervention reversed those changes（ P 〈0. 01）. Conclusion The administration of octreotide can ameliorate abnormal enhancement of hepatic gluconeogenesis,which might be attributed to the reduced activity and expression of Foxo1 and then decreased expression levels of G6 pase and Pepck mRNA.

关 键 词：糖异生 奥曲肽 葡萄糖-6-磷酸酶 磷酸烯醇式丙酮酸羧激酶 叉头框家族转录因子1 

分 类 号：R587[医药卫生—内分泌] Q591.4[医药卫生—内科学]