摘要
目的观察利拉鲁肽对糖尿病肾病大鼠肾组织Toll样受体(TLR) 4/髓样细胞分化因子(MyD) 88信号转导通路中炎症因子的影响。方法健康SD雄性大鼠68只,随机分为正常对照组、模型组、利拉鲁肽组、二甲双胍组,每组17只。采用高脂高糖饮食饲养联合腹腔注射少量链脲佐菌素(STZ)法制备大鼠糖尿病肾病模型。利拉鲁肽组按0. 12 mg·kg~(-1)·d~(-1)的剂量皮下注射给药,二甲双胍组按140 mg·kg~(-1)·d~(-1)的剂量灌胃给药,正常对照组及模型组均给予等量溶媒,实验期间各组大鼠均无降糖干预,饲养8 w。检测尿蛋白、尿糖及血生化,苏木素-伊红(HE)染色观察大鼠肾组织形态学改变,免疫组化检测TLR4/MyD88蛋白表达,酶联免疫吸附试验(ELISA)检测大鼠肾组织核因子(NB)-κB、肿瘤坏死因子(TNF)-α及白细胞介素(IL)-6含量。结果与正常对照组相比,模型组、利拉鲁肽组、二甲双胍组24 h尿蛋白含量、24 h尿糖、血肌酐、尿素氮及血糖水平明显升高,TLR4/MyD88蛋白表达明显增多,NB-κB、TNF-α、IL-6含量明显上升(均P<0. 05)。与模型组相比,利拉鲁肽组、二甲双胍组24 h尿蛋白含量、24 h尿糖、血肌酐、尿素氮及血糖明显下降,TLR4/MyD88蛋白表达明显降低(P<0. 05),NB-κB、TNF-α、IL-6表达明显下降(P<0. 05)。结论利拉鲁肽能对糖尿病大鼠肾脏产生保护,其机制可能与其通过调控TLR4/MyD88信号通路抑制炎症因子NB-κB、TNF-α、IL-6的表达有关。
Objective To observe the effect of liraglutide on TLR4/MyD88 path renal tissue of diabetic rats and provide a way to treat diabetic nephropathy.Methods 68 SD Wistar rats were randomly divided into normal control,model and liraglutide,metformin groups,17 in each group. Model of diabetic nephropathy was made by combined high fat and sugar diet feeding with intraperitoneal injection of a small dose of STZ. Rats were given 0.12 mg·kg-1·d-1 liraglutide subcutaneously in liraglutide group,140 mg·kg-1·d-1 metformin lavage metformin group,the same amount of solvent in normal control,model groups. All rats in the experimental period should be fed for 8 weeks without insulin. 24 hours urine protein,24 hours urine sugar,serum creatinine,blood urea nitrogen and blood sugar levels were measured and under optical microscope after HE staining in the rat kidney tissue morphology change was observed,TLR4/MyD88 protein expression was detected by immunohistochemistry,NF-κB,TNF-α and IL-6 content in rat kidney were measured by ELISA. Results Compared with normal control group,24 hours urinary protein,24 hours urine sugar,serum creatinine,blood urea nitrogen were elevated,TLR4/MyD88 protein expression were increased,NB-κB,TNF-α,IL-6 expression were decreased( all P < 0. 05) in model,liraglutide and metformin groups. Compared with model group,24 hours urinary protein,24 hours urine sugar,serum creatinine,blood urea nitrogen and blood sugar drops,TLR4/MyD88 protein were decreased,NB-κB,TNF-α,IL-6 expression were increased( all P< 0.05) in liraglutide and metformin groups.Conclusions Liraglutide could protect the kidneys of diabetic rats,the mechanism may be related with regulation of TLR4/MyD88 signaling pathway,inhibiting inflammatory cytokines NB-κB,TNF-α and IL-6.
引文
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