利拉鲁肽对糖尿病大鼠肾组织高迁移率族蛋白B1表达影响的研究

Effects of Liraglutide on expression of high mobility group box-1 in renal tissues of diabetic rats

目的观察利拉鲁肽对糖尿病大鼠肾组织高迁移率族蛋白B1(HMGB1)表达水平的影响,探讨利拉鲁肽对DKD的保护作用及机制。方法 40只健康雄性SD大鼠随机分为正常对照(NC)组、利拉鲁肽治疗(Lira)组、糖尿病(DM)组、糖尿病+利拉鲁肽治疗(DM+Lira)组,每组各10只。采用一次性腹腔注射STZ 60 mg/kg制备T1DM大鼠模型。Lira、DM+Lira组每24 h予腹腔注射利拉鲁肽200μg/kg,NC、DM组予腹腔注射等量生理盐水。治疗8周后检测大鼠体重、FPG;ELISA法检测24 h UAlb;HE、PAS染色观察各组病理形态学改变;免疫组织化学法检测肾组织CD14表达水平;Western blot法检测肾组织HMGB1及Toll样受体4(TLR-4)蛋白表达水平。结果与DM组比较,DM+Lira组24 h UAlb、肾小球及肾小管CD14水平降低(P<0. 01),病理损伤减轻,HMGB1[(0. 98±0. 04)vs(0. 78±0. 01)]及TLR-4[(0. 93±0. 01)vs(0. 76±0. 02)]蛋白表达降低(P<0. 01),体重及FPG水平差异无统计学意义(P>0. 05)。结论利拉鲁肽能改善糖尿病大鼠肾损伤,其机制可能与抑制HMGB1表达从而减轻炎症反应有关。

Objective To investigate the effects of Liraglutide on expression of high mobility group box-1(HMGB1)in the renal tissues of diabetic rats and to explore the protective effects of Liraglutide on diabetic kidney disease and the possible mechanisms.ed into four groups:normal control group(NC group),normal control + Liraglutide treatment(Lira group),diabetes group(DM group),and diabetes + Liraglutide treatment(DM+Lira group). Type 1 diabetes mellitus(T1DM)model was induced by intraperitoneal injection of streptozotocin(STZ,60 mg/kg).Lira and DM + Lira group recieved intraperitoneal injection with Liraglutide[200 μg/(kg·d)],while NC and DM group recieved intraperitoneal injection with the same amount of phosphate buffer. Body weight and fasting blood glucose(FPG)were tested after 8 weeks of treatment. Microalbuminuria(UAlb)was detected by ELISA. The pathological changes of the kidney were evaluated by HE staining and PAS staining.CD14 expression in the kidney was analyzed by immunohistochemistry. The expressions of HMGB1 and tolllike receptor 4(TLR-4)were evaluated by Western blot.Results CD14 in glomeruli and tubular were all significantly decreased in DM + Lira group than in DM group(P<0. 01). Morphological abnormality was also significantly ameliorated in DM + Lira group than in DM group(P<0. 01). Furthermore,the protein expressions of HMGB1[(0. 98±0. 04)vs(0. 78±0. 01)]and TLR-4[(0. 93±0. 01)vs(0. 76±0. 02)]were significantly down-regulated in DM + Lira group than in DM group(P<0. 01). But there was no significant difference in FPG and body weight(P>0. 05).Conclusion Liraglutide could attenuate the kidney tissue damage in STZ-induced diabetic rats,which may be related to the inhibition of HMGB1 and inflammatory responses.