摘要
目的探究利拉鲁肽在糖尿病致肾脏纤维化过程中的影响及作用机制。方法随机选取大鼠20只,为正常组(NC组);40只经高脂高糖结合链脲佐菌素注射复制糖尿病大鼠模型,再随机分为糖尿病组(DM组)、利拉鲁肽组(LR组);利拉鲁肽皮下注射,0.15 mg·(kg·d)-1,正常组、糖尿病组给予等体积的溶媒。给药8周后检测24 h尿蛋白排泄(24 h UP)、尿素氮(BUN)、血清肌酐(SCr)水平。光镜下观察大鼠肾脏病理。Toll样受体4由免疫组化法检测。酶联免疫吸附测定(ELISA)检测转化生长因子-β1、结缔组织生长因子含量。结果与正常组比较,利拉鲁肽组24 h尿蛋白排泄、尿素氮、血清肌酐水平升高(P<0.05),Toll样受体4表达增加(P<0.05),肾脏纤维化程度加深;与糖尿病组比较,利拉鲁肽组24 h尿蛋白排泄、尿素氮、血清肌酐水平下降(P<0.05),Toll样受体4表达减少(P<0.05),纤维化程度好转。结论利拉鲁肽能够改善肾脏纤维化,其机制可能与抑制Toll样受体4通路有关。
Objective To explore the effect and mechanism of liraglutide in diabetes-induced renal fibrosis process.Methods 20 rats were randomly selected as the normal group（NC group）; 40 rats were randomly selected to build DM rat model by the way which injected with high-fat and high-sugar combined with streptozotocin to replicate,then the 40 rats were randomly divided into diabetic group（DM）,liraglutide group（LR group）; LR subcutaneous liraglutide group,0. 15mg·（kg·d）^-1,NC group,DM group was given the same amount of solvent.Observeing the change of rat kidney tissue morphology.Immunohistochemical detection TLR4 protein molecule expression. ELISA method detected the levels of TGF-β1,CTGF.Results Compared with NC group,the 24 h UP,BUN,SCr levels of LR group was increased（P 0. 05）,the TLR4 expression of LR group was increased（P0.05）,renal fibrosis deepened; Compared with DM group,LR group,the 24 h UP,BUN,SCr levels of LR group decreased（P0.05）,the TLR4 expression of LR group was increased（P0.05）,fibrosis improved.Conclusion Liraglutide can improve renal fibrosis,which may be related to inhibiting TLR4 pathway.
出处
《药学研究》
CAS
2017年第1期6-8,共3页
Journal of Pharmaceutical Research
基金
国家级大学生创新创业训练计划项目(No.201606)
