二甲双胍与西格列汀对非酒精性脂肪肝病大鼠肝脏FGF21及SREBP-1cmRNA表达的影响

摘要

目的：比较二甲双胍及西格列汀对高脂饮食诱导大鼠肝脏 FGF21 mRNA及SREBP-1c mRNA的作用。方法将60只SD大鼠随机分为正常组20只（普通饲料，NC组）及高脂组40只（高脂饮食，HF组），喂养8周后，每组随机抽取10只，比较后证实HF组NAFLD模型成功建立。继将HF组分3组：二甲双胍干预组（ HF﹢M，10只）[加二甲双胍500 mg／（ kg·d）]、西格列汀干预组（ HF﹢XI，10只）[加西格列汀10 mg／（ kg·d）]及高脂组（ HF1，10只）（等体积生理盐水）。灌胃8周末处死，检测血清丙氨酸氨基转移酶（ ALT）、天冬氨酸氨基转移酶（ AST）、总胆固醇（ TC）、三酰甘油（ TG）、游离脂肪酸（ FFA）含量，空腹血糖（ FBG）及胰岛素（ FINS）水平，计算胰岛素抵抗指数（ HOMA-IR）；HE染色观察肝脏病理形态学的变化；Real-time PCR检测肝组织FGF21 mR-NA及SREBP-1c mRNA表达的变化。结果两种药物均可降低血清ALT、AST活性（P﹤0.05），减少TC、TG、FFA含量，FBG、肝脏TG含量及HOMA-IR（ P﹤0.05）；西格列汀可明显改善大鼠肝脏脂肪变，效果优于二甲双胍；二甲双胍可下调肝组织SREBP-1c mRNA表达量，上调FGF21 mRNA表达量（ P﹤0.01），而西格列汀可同时降低肝脏FGF21 mRNA及SREBP-1c mRNA表达量（P﹤0.01）。结论西格列汀与二甲双胍均可有效减少肝脏TG含量，但西格列汀改善肝组织病理变化较二甲双胍明显，而二甲双胍减轻 HOMA-IR强于西格列汀；同时，二者均可不同程度影响肝组织SREBP-1c与FGF21 mRNA表达量。%Objective To compare the effect of metformin and sitagliptin on the expression of liver SREBP-1c mRNA and FGF21 mRNA in rats induced by high fat-diet. Methods Sixty SD rats were randomly divided into two groups:normal control group( NC group,n =20,fed with normal diet),high fat group( HF group,n =40,fed with high fat diet),after 8-week feeding,10 rats were randomly selected from two groups respectively,and NAFLD model of HF group was confirmed to be built successfully compared with NC group. Rats in HF group was divided into 3 groups:metformin treatment group(HF﹢M,n=10)[plus metformin 500 mg/(kg·d)],sitagliptin treatment group (HF﹢XI,n=10)[only sitagliptin 10 mg/(kg·d)]and HF1 group(n=10)(only an equal volume of saline). The serum contents of alanine transferase( ALT),aspartate aminotransferase( AST),total cholesterol( TC),total glyceride ( TG)and free fatty acid( FFA)were detected after 8-week lavage;the fasting serum glucose and insulin( FINS)level were measured and the insulin resistance index( HOMA-IR)was calculated;HE staining was carried out to observe the liver pathological changes and the expression levels of FGF21 and SREBP-1c mRNA were measured using Real-time PCR. Results In all treatment groups,the serum content of ALT,AST,TC,TG,FFA and TG and HOMA-IR were re-duced significantly( P﹤0. 05),the pathological changes of the rat liver were reduced significantly by sitagliptin,which was significantly better than metformin,the expression of SREBP-1c mRNA in the liver was reduced by the metformin and FGF21 mRNA was increased,but the expression of SREBP-1c mRNA and FGF21 mRNA in the liver was also re-duced significantly by sitagliptin(P﹤0. 01). Conclusion Sitagliptin and metformin can effectively reduce the content of TG in the liver,but the liver pathological changes improved by sitagliptin are better than by metformin,while met-formin can reduce HOMA-IR more significantly than sitagliptin;and both of them can change SREBP-1c and FGF21 mRNA expression in the liver tissue in different degree.