奥沙利铂对大鼠下丘脑及外周血中Ghrelin表达的影响

Effects of oxaliplatin on the expression of ghrelin in rat hypothalamus and serum

目的:研究化疗药物奥沙利铂对大鼠下丘脑中神经肽Ghrelin表达水平的影响。方法:SD大鼠分为对照组和奥沙利铂处理组,观察各组大鼠摄食量变化。real-timeRT-PCR检测各组大鼠下丘脑中GhrelinmRNA表达变化,免疫组化和WesternBlot方法检测大鼠下丘脑中Ghrelin蛋白的表达水平。结果:奥沙利铂化疗后,大鼠第2~4d摄食量减少。奥沙利铂化疗后大鼠血浆酰化Ghrelin浓度显著下降。化疗后第3d大鼠血浆酰化ghrelin为52.5±2.1pmol/l,显著低于NS对照组86.5±4.7pmol/l(P<0.05)。奥沙利铂化疗后大鼠下丘脑内GhrelinmRNA及蛋白表达水平在第1、3d和5d均下降,其中第3d下降最显著。结论:奥沙利铂化疗可降低大鼠食欲,降低Ghrelin在下丘脑中的表达。

Objectives: To explore the effects of oxaliplatin on the expression of ghrelin in the rat hypothalamu.Methods: SD rats were divided into two groups: oxaliplatin treated group and Control group.The food intake of the rats was evaluated.The serum ghrelin level in the rats was measured using ELISA.Ghrelin mRNA expression in rats hypothalamus was detected with real-time RT-PCR.Ghrelin protein expression was investigated by Western Blot and immunohistochemistry.Results: The food intake was decreased in rats on day 2 to day 4 after oxaliplatin injection.The acylated ghrelin level in rats serum was prominantly decreased in the oxaliplatin treatment group compared with that in the control group on the third day ( 52.5 ± 2.1 pmol /l vs 86.5 ± 4.7 pmol /l,P<0.05) .Both ghrelin mRNA and protein level in the rats hypothalamus were reduced after oxaliplatin treatment and reached the bottom level on the third day.Conclusions: Oxaliplatin induced reduction of rat appetite,and decreased the expression of ghrelin in hypothalamus.