利拉鲁肽对非酒精性脂肪性胰腺病小鼠的内质网应激相关蛋白的调控作用研究

Regulation of liraglutide on endoplasmic reticulum stress related proteins in mice with non-alcoholic fatty pancreatic disease

目的研究利拉鲁肽对非酒精性脂肪胰腺病(NAFPD)小鼠作用及可能机制。方法按照体重将小鼠随机分为3组:正常组、模型组和实验组,每组10只。模型组和实验组的小鼠以高脂饲料喂养16周建立NAFPD模型。实验组小鼠腹腔注射利拉鲁肽0.6 mg·kg^-1·d^-1,正常组与模型组小鼠腹腔注射等体积0.9%NaCl。用免疫印迹法测定胰腺组织中R样内质网激酶(PERK)、真核翻译起始因子2α(EIF2α)和转录活化因子4(ATF4)等内质网应激(ERS)相关蛋白表达水平。结果正常组、模型组和实验组的平均体重分别为(29.10±2.37),(36.10±2.73)和(28.50±1.58)g;这3组的PERK蛋白相对表达量分别为0.14±0.42,0.61±0.26和0.21±0.13;这3组的EIF2α蛋白的相对表达量分别为0.20±0.12,1.62±1.41和0.40±0.19;这3组的ATF4蛋白的相对表达量分别为0.39±0.23,1.82±1.42和0.52±0.19。上述指标:模型组与正常组相比、或者实验组与模型组相比,差异均有统计学意义(P<0.05,P<0.01)。结论ERS可能是NAFPD的发病机制之一。利拉鲁肽可能通过调控PERK-EIF2α-ATF4通路来抑制ERS,从而可能具有改善NAFPD的作用。

Objective To observe the effect and possible mechanism of liraglutide on non-alcoholic fatty pancreatic disease(NAFPD)in mice.Methods The mice were divided into three groups:normal group,model group and experimental group,with 10 mice in each group.Mice in model group and experimental group were fed with high-fat diet for 16 weeks for establishment of NAFPD model.Mice in experimental group were given intraperitoneal injection liraglutide 0.6 mg·kg-1·d-1 for 4 weeks.Normal group and model group were treated with equal volume of normal saline.The protein expression levels of kinase R-like endoplasmic reti-culum kinase(PERK),eukaryotic translation initiation factor 2α(EIF2α),activating transcription factor4(ATF4)of the endoplasmic reticulum stress(ERS)related protein were detected by Western blot.Results The weights in normal group,model group and experimental group were(29.10±2.37),(36.10±2.73),(28.50±1.58)g,respectively;the relative expression of PERK protein in the three groups were 0.14±0.42,0.61±0.26,0.21±0.13,respectively;the relative expression of EIF2αprotein in the three groups were 0.20±0.12,1.62±1.41,0.40±0.19,respectively;the relative expression of ATF4 protein in the three groups were 0.39±0.23,1.82±1.42,0.52±0.19.Significant differences of the factors were found between normal group and model group(P<0.05,P<0.01);also between experimental group and model group(P<0.05,P<0.01).Conclusion The ERS may be one of the pathogenesis of NAFPD.And liraglutide can restrain ERS by regulating PERK-EIF2α-ATF4 pathway in mice with NAFPD.