降糖及调脂治疗对OLETF大鼠血浆和胃组织中ghrelin水平的影响

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200 mg/(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 blotting检测胃组织中ghrelin的Mrna水平.结果: (1) 30周龄时,OLETF大鼠每100 Μl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.

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

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 didn't 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 tissue of OLETF/F group were markedly higher than those of stomach tissue ghrelin in the untreated OLETF group. CONCLUSION:Our data demonstrate that ghrelin may play a role in protective, compensative and negative-feedback regulation in the disorder of glucose and lipid metabolism.