利拉鲁肽对非酒精性脂肪肝大鼠胰岛素抵抗的改善作用

Effects of liraglutide on insulin resistance in rats with nonalcoholic fatty liver disease

目的研究利拉鲁肽对非酒精性脂肪性肝病(NAFLD)大鼠胰岛素抵抗(IR)的改善作用。方法取SD大鼠50只,采用高脂饲料喂养法建立NAFLD大鼠模型,将造模成功的32只大鼠随机分为4组,即模型组(A组,n=8),其余3组为不同剂量利拉鲁肽处理组,包括B组【0.9 mg·kg^(-1)·d^(-1),n=8】、C组【(1.8 mg·kg^(-1)·d^(-1)),n=8】和D组【(3.6 mg·kg^(-1)·d^(-1),n=8】。在药物干预4 w后,取血和肝脏,制备肝组织匀浆,分别测定大鼠体质量、肝质量、肝指数、血糖、胰岛素(FINS)、血脂(TG、TC)、转氨酶(ALT、AST)、血清丙二醛(MDA)、谷胱甘肽氧化酶(GSH-Px)、肝组织超氧化歧化酶(SOD)、肿瘤坏死因子α(TNF-α)水平。结果与模型组比,药物干预后大鼠体质量、肝指数、血ALT、FINS、FPG、HOMA-IR、MDA和肝组织TG、TC、MDA水平均显著下降(P<0.05),大剂量组上述指标下降显著高于中小剂量组(P<0.05);与模型组比,药物干预后大鼠肝组织GSH-Px和SOD水平均显著升高(P<0.05),且大剂量组升高明显高于中小剂量组(P<0.05);各组间TNF-α变化无明显差异(P>0.05)。结论利拉鲁肽能显著降低NAFLD大鼠血脂和血糖水平,改善IR,治疗作用呈明显的剂量相关性。

Objective To study the effect of different doses of liraglutide on insulin resistance （IR）in modelrats with nonalcoholic fatty liver disease（NAFLD） . Methods High fat diet was given to 50 male Sprague-Dawleyrats to establish NAFLD and 32 rats with successful NAFLD were randomly divided into4 groups, e.g. groupA（model group, n=8）, and liraglutide were given in groupB [0.9 mg · kg-1· d-1, n=8], groupC [1.8 mg· kg-1·d-1, n=8] andgroupD [3.6 mg · kg-1· d-1, n=8]. Rats were sacrificed after 4 weeks of medicine intervention. Data of body weight andliver weight were recorded. Blood from the abdominal aorta and livers were collected. Liver index, blood glucose,insuli （FINS）, blood lipids（TG, TC）, transaminase（ALT, AST）, malondialdehyde （MDA）, and glutathione peroxidase（GSH-Px）, superoxide dismutase （SOD） and tumor necrosis factor alpha （TNF-alpha） in liver tissues weredetected. Results Compared with in the model group, the rat body weight, liver index, ALT, FINS, FPG, HOMA-IR,MDA in blood and TG, TC, MDA in liver tissues decreased significantly in intervention groups（P〈0.05）, and in groupD with highest dose of liraglutide gained the most decrease in the above index than in the other two interventiongroups （P〈0.05） ; Compared with in model group,the GSH-Px and SOD in intervention groups significantly increased（P〈0.05）, and GSH-Px and SOD in group D increased the most（P〈0.05） ; There was no significant difference ofTNF-α among all the groups. Conclusion Liraglutide can significantly reduce the liver index,serum lipid andblood glucose in rats with NAFLD, and improve IR, and the treatment effect is dose-dependent.