糖尿病肾病模型中NF-κB与甘露聚糖结合凝集素途径补体激活的关系

Relationship Between Activation of Mannan-binding Lectin Complement and NF-κB in Diabetic Nephropathy

目的通过链脲佐菌素(STZ)制备糖尿病肾病大鼠模型,了解糖尿病肾病时甘露聚糖结合凝集素(MBL)途径补体激活情况及其与核转录因子κB(NF-κB)的关系。方法将SD大鼠分为正常对照组(N组)和糖尿病肾病组(DN组)。DN组按55 mg/kg体质量一次性腹腔注射1% STZ,N组一次性腹腔注射等量柠檬酸缓冲液。于实验1、2、4、8周分别处死两组各5只大鼠,测量大鼠的血糖、24 h尿量、24 h尿白蛋白量、24 h尿肌酐、血清肌酐、体质量和肾脏质量,计算肌酐清除率和肾脏肥大指数,采用免疫组化SP法观察各组大鼠1、2、4、8周肾组织MBL,膜攻击复合物(MAC)及NF-κB的表达。结果与正常组相比,DN组大鼠肾小球MBL沉积增多,MAC,NF-κB表达明显增多(P<0.05),并随时间推移继续增高,各时间点差异有统计学意义(P<0.05)。STZ腹腔注射所致DN组大鼠的肾小球MBL,NF-κB的表达水平成显著正相关(r=0.973,P<0.01)。结论甘露聚糖结合凝集素途径的补体激活参与了糖尿病肾病的发生发展,可能为下一步的诊断治疗提供新的方向。

Objective To study the activation of mannose-binding lectin（MBL） complement in STZ-induced diabetic nephropathy（DN） rats and its relationship with NF-κB.Methods Sprague-Dawley（SD） rats were randomLy divided into two groups： normal control and diabetic nephropathy.Diabetes was induced by intraperitoneal injection of STZ.Five rats were sacrificed at the end of week 1,2,4,8 respectively.Blood glucose,24 h urine,24 h urinary albumin,serum creatinine（Scr）,body mass and kidney mass were examined at the same time points respectively.Creatinine clearance and renal hypertrophy index were calculated.The renal expression of MBL,membrane attack complex（MAC） and NF-κB were determined by immunohistochemistry.Result MBL,MAC and NF-κB expression were significantly increased in glomerulus of diabetic nephropathy rats compared to the controls.The expression of MBL was positively correlated with NF-κB expression.Conclusion The activation of mannose-binding lectin complement participates in the onset and development of DN.