降糖及调脂治疗对OLETF大鼠血浆和胃组织中ghrelin水平的影响

Change in ghrelin level with the amelioration of glucose and lipid metabolic disorder in OLETF rats

目的:探讨ghrelin与糖脂代谢的关系。方法:8周龄OLETF大鼠分别为未治组(n=10)、二甲双胍[200mg/(kg.d)]治疗组(n=10)、微粒化非诺贝特[20 mg/(kg.d)]治疗组(n=10),同周龄LETO大鼠(n=10)为正常对照。用放射免疫法测定胃组织及血浆ghrelin水平,以Northern b lotting检测胃组织中ghrelin的mRNA水平。结果:(1)30周龄时,OLETF大鼠每100μL空腹血浆ghrelin的质量(pg)显著低于LETO大鼠(37.49±6.42比58.52±5.85,P<0.01),二甲双胍有增加OLETF大鼠ghrelin空腹血浆浓度的趋势,但与未治组间差异无统计学意义(49.65±6.76比37.49±6.42,P>0.05),非诺贝特治疗组在30周龄时显著高于未治组(62.02±7.35比37.49±6.42,P<0.05)。(2)胃组织中每微克蛋白ghrelin的多肽(pg)和mRNA水平,17周龄时各组间均差异无统计学意义;30周龄时,OLETF大鼠均显著低于LETO组[mRNA(1.18±0.06比1.27±0.05,P<0.05),多肽(114.77±31.65比152.87±18.24,P<0.05)];二甲双胍治疗组与未治组间差异无统计学意义;非诺贝特治疗组显著高于未治组[mRNA(1.36±0.09比1.18±0.06,P<0.05),多肽(161.75±23.61比114.77±31.65,P<0.05)]。结论:ghrelin可能对糖脂代谢的紊乱起一种保护性的、代偿性的负调节作用。

Objective： To explore the exact role of ghrelin in glyco- and lipo-metabolism. Methods： We compared the levels of ghrelin mRNA in gastric tissue, ghrelin in gastric tissue and plasma among LETO rats（ non diabetes, n = 10）, OLETF rats（ type 2 diabetes, n = 10）, OLETF/M rats（ OLETF rats managed with Metformin at the dose of 100 mg/kg weight, n = 10） and OLETF/F rats（ OLETF rats managed with Fenofibrate at the dose of 20 mg/kg weight, n = 10）. The levels of ghrelin mRNA were tested by Northern blotting, and the ghrelin content in gastric tissue and plasma detected by RIA. Results： At the age of 30 weeks, the ghrelin fasting plasma levels of OLETF rats were lower than those of LETO rats （37.49± 6.42 vs 58.52±5.85, P 〈 0.05 ）. The fasting blood plasma ghrelin levels of OLETF/M groups showed an increased tendency, but the difference of the fasting blood plasma ghrelin levels to those of the untreated OLETF rats were not noticeable （49.65±6.76 vs 37.49±6.42, P 〉 0.05 ）. However, the fasting blood plasma ghrelin levels of OLETF/F group were more than those that of the untreated OLETF rats （62.02 ±7.35 vs 37.49 ±6.42 ,P 〈0.05 ）. The mRNA and polypeptide levels of ghrelin in stomach tissue had no marked difference in the 4 groups at the age of 17 weeks. At the age of 30 weeks, the difference of mRNA（ 1.18 ± 0.06 vs 1.27± 0. 05, P 〈 0.05 ） and polypeptide （ 114.77 ±31.65 vs 152.87 ± 18. 24, P 〈0.05） between OLETF group and LETO group had been observed. Metformin didnt influence the mRNA and polypeptide levels of ghrelin in stomach tissue markedly. Howere, the polypeptide （161.75±23.61 vs 114.77±31.65, P 〈0.05） and mRNA（1.36±0.09 vs 1.18 ± 0.06 ,P 〈 0.05 ） levels of ghrelin in stomach tiss.ue of OLETF/F group were markedly higher than those of stomach tissue ghrelin in the untreated OLETF group. Concluslon：Our data demonstrate that ghrelin may play a role in protective, compensative and negative-feedback regulation in the disorder of glucose and lipid metabolism.