二甲双胍对肥胖大鼠血清及下丘脑中胃促生长素表达的影响

目的观察肥胖大鼠血清及下丘脑中胃促生长素水平在二甲双胍干预前后的变化,探讨其在肥胖及代谢紊乱中的作用。方法 SD大鼠50只随机分为普通饮食(NC,n=10)组和高脂(n=40)组,16周高脂组成功建立肥胖模型后(n=20)随机分为:肥胖对照(OB)组,二甲双胍(MET)组,各10只。MET组灌胃MET 200 mg/(kg.d),OB组及NC组灌胃等剂量蒸馏水。分别测定干预前及干预6周后各组体重(BW)、空腹血糖(FPG)、甘油三酯(TG)、总胆固醇(TCH)、空腹胰岛素(FINS)、胰岛素抵抗指(HOMA-IR)及胃促生长素。免疫组化法检测各组大鼠下丘脑中胃促生长素表达水平。结果①干预前,OB组、MET组较NC组BW、FPG、TG、TCH、FINS、HOMA-IR升高,胃促生长素降低(P<0.05,P<0.01),OB组、MET组间各指标比较差异无统计学意义。MET干预后,MET组较OB组BW、TG、TCH、FPG、FINS、HOMA-IR降低,胃促生长素水平升高(P<0.05,P<0.01)。②免疫组化显示:OB组下丘脑中胃促生长素表达较NC组降低,MET组较OB组升高,差异有统计学意义(P<0.05,P<0.01)。③研究总体中FINS与胃促生长素呈负相关(r=-0.817,P<0.05)。结论肥胖大鼠血清及下丘脑胃促生长素水平降低,MET可改善胰岛素敏感性、降低BW,可能与血清及下丘脑胃促生长素水平增高有关。

Effects of metformin on ghrelin levels in serum and hypothalamus of high-diet fed obesity rats

Objective To observe the change of ghrelin levels in serum and hypothalamus in high-diet fed obesity rats before and after the treatment of metformin,and to investigate the relationship of ghrelin between obesity and metabolic syndrome.Methods 50 SD rats were randomly divided into normal diet group NC(n=10) and high fat diet group(HD n=40).Obesity model was established by HD group(n=20),assigned obesity group(OB,n=10),and metformin group(MET,n=10).MET group was treated with metformin 200 mg/(kg·d) and the other two groups were treated with distilled water.Body weight(BW),fasting plasma glucose(FPG),triglyceride(TG),total cholesterol(TCH),fasting insulin(FINS),HOMA index and fasting ghrelin were measured before and after 6 weeks treated.Ghrelin expression in hypothalamus was detected by immunohistochemistry.Results ① BW,FPG,TG,TCH,FINS levels and HOMA-IR in OB group and MET group increased and ghrelin levels decreased in contrast to those in NC group(P<0.05,P<0.01) before treatment.After treat with metformin,BW,FPG,TG,TCH,FINS levels and HOMA-IR of MET group decreased and ghrelin levels increased in contrast to those in OB group(P<0.05,P<0.01).② Ghrelin expression levels in hypothalamus of OB group increased and that of MET group was down-regulated with statistical difference(P<0.05,P<0.01).③ The level of FINS was negatively correlated with that of ghrelin(r=-0.817,P<0.05).Conclusion Ghrelin levels in serum and hypothalamus of obesity rats decrease.Metformin can improve insulin resistence and reduce body weight,which may plays roles in increasing ghrelin levels in serum and hypothalamus.