Ghrelin对糖尿病大鼠摄食的影响

目的探讨Ghrelin在糖尿病大鼠摄食过量调控中的作用。方法21只大鼠随机分为：①正常对照组（N＋NS组）7只，腹腔注射枸橼酸缓冲液1mL，皮下注射生理盐水（NS）0．1mL；②实验组14只，采用链脲佐菌素（sTz）腹腔注射制作糖尿病大鼠模型，48h后随机分为糖尿病组（STZ＋NS组）7只，皮下注射NS0．1mL，糖尿病＋胰岛素组（sTz＋INS组）7只，皮下注射人胰岛素0．1mL（7U）。各组均每天注射2次，共注射14d。每天检测各组大鼠血糖水平、摄食量及体质量的改变；实验结束检测血清瘦素、生长激素水平，以及下丘脑神经肽Y（NPY）mRNA和胃GhrelinmRNA表达。结果注射STZ后5d，STZ＋NS组血糖水平持续高于27．8mmol／L；STZ＋INS组血糖水平逐渐下降，最终在8d后与N＋NS组无显著差异（P〉0．05）；STZ＋NS组摄食量较N＋NS组显著增多，体质量显著减少（F一9．56～29．25，q一6．46～9．56，P〈O．05）；STZ＋INS组与STZ＋NS组比较，大鼠摄食量显著减少，体质量显著增加（q=3．70～9．15，P％0．05）。与N＋NS组相比，STZ＋NS组血浆胰岛素、瘦素及生长激素水平显著降低，而STZ＋INS组血浆瘦素及生长激素水平显著升高（F=26．31～214．28，q=3．21～11．28，P〈0．05）。STZ＋NS组血浆Ghrelin水平显著高于N＋Ns组（F=52．31，q=12．41，P〈0．05），STZ＋INS组血浆Ghrelin水平趋于正常（P〉0．05）。STZ＋NS组下丘脑NPYmRNA表达较N＋NS组显著增高（F=97．96，q—17．78，P〈O．05）。结论糖尿病大鼠血浆Ghrelin、瘦素水平以及下丘脑NPY表达的改变，可能与糖尿病摄食过盛形成有关。

EFFECTS OF GHRELIN ON FOOD INTAKE IN DIABETIC RATS

Objective To explore the effects of Ghrelin on regulating hyperphagia in diabetic rats. Methods Twenty- one rats were divided into two groups as normal control group （N＋NS, 7 rats）--intraperitoneal injection of citric acid buffer solu- tion 1 mL, and subcutaneous injection of normal saline 0.1 mL; experimental group （14 rats） a diabetic model was created by using intraperitoneal injection of streptozotocin （STZ）, the rats were then, 48 h later, equally randomized to diabetic group （STZ＋NS）, they were subcutaneously injected NS 0.1 mL, twice a day for 14 days, and diabetes＋insulin group （STZ＋INS）, subcutaneous in- jection of insulin 0.1 mL （7 U）, twice a day for 14 days. Blood glucose levels, food intake, body weight were measured, and the levels of serum leptin and growth hormone, the expressions of NPY mRNA in hypothalamus and gastric Ghrelin mRNA were de- tected in each groups. Results Five days after injection of STZ, the blood glucose level in STZ＋NS group was lasting above 27.8 mmol/L, that in STZ＋INS group declined gradually, eight days later, the difference was not significant as compared with the N＋NS group （P〉0.05）. Five days after injection of STZ, the food intake of rats in STZ＋ NS group was increased more than those in the N＋NS group, and the body weigh decreased （F=9.56-29.25,q=6.46-9.56,P〈0.05）, the food intake in rats in the STZ＋INS group was reduced, and the body weight increased as compared with those in the STZ＋NS group （q=3.70--9.15, P〈0.05）. Compared with the N＋NS group, the levels of plasma insulin, leptin and the growth hormone in the STZ＋NS group were lower, and the levels of leptin and growth hormone in the STZ＋ INS group elevated （F = 26.31- 214.28, q = 3.21-11.28, P〈0.05）. The plasma Ghrelin level in the STZ--NS group was higher than that in the N＋ NS group（F=52.31 ,q ： 12.41, P 0.05）, and that in the STZ＋INS group tended to be normal （P〉0.05）. The hypothalamic NPY mRNA expression in rats of the STZ＋NS group was much higher than those in the N＋NS group （F=97.96,q=17.78,P〈0.05）. Conclusion The changes of the levels of plasma Ghrelin and leptin levels and the expression of gastric Ghrelin are likely to be associated with hyperphagia in the diabetic rats.