新一代免疫抑制剂依维莫司对db/db小鼠的肾脏保护作用

Protective effect of everolimus on kidney in db/db diabetic mice

目的:观察哺乳类动物雷帕霉素靶蛋白(mTOR)抑制剂依维莫司对糖尿病肾病的保护作用。方法:12只db/m非糖尿病小鼠和12只db/db糖尿病小鼠被随机分为四组,每组6只,分别为db/m非糖尿病小鼠组,db/m非糖尿病小鼠加依维莫司组,db/db糖尿病小鼠组,db/db糖尿病小鼠加依维莫司组。依维莫司治疗剂量为2mg/kg.d,给药时间8周。实验结束后,从眶后静脉丛取血用于生化检查。取小鼠肾脏用于组织学检查。结果:与db/m非糖尿病小鼠比较,db/db糖尿病小鼠血肌酐[(45.4±2.1)μmol/L比(94.3±4.7)μmol/L]、尿素氮水平[(5.96±0.28)mmol/L比(10.58±0.88)mmol/L]明显升高,肾脏重量[(156.67±4.97)g比(182.50±5.47)g]、肾小球面积[(3934±329)μm2比(6586±347)μm2]都明显增大,且肾小球系膜区细胞外基质也明显增多[(21.0±1.5)%比(36.7±2.2)%]。接受依维莫司治疗的糖尿病小鼠,血肌酐(63.2±4.2)μmol/L,尿素氮(7.55±0.62)mmol/L,肾脏重量(163.50±4.64)g,肾小球面积(4663±252)μm2显著下降(P<0.05)。结论:依维莫司能够延缓糖尿病肾病的进展。

Objective：To observe the protective effect of mammalian target of rapamycin（mTOR） inhibitor everolimus on diabetic nephropathy.Methods：A total of 12 db/m no-diabetes mellitus（DM） mice and 12 db/db DM mice were randomly and equally divided into four groups：db/m no-DM mice group,db/m no-DM mice＋everolimus group,db/db DM mice group,db/db DM mice＋everolimus group.Everolimus were given 2mg /kg·d,eight weeks for correspohding group of mice.After experiment,blood samples were withdrawn from vena orbitalis posterior for biochemical analysis and kidneys of mice were used for histological analysis.Results：Compared with db/m no-DM mice,levels of serum creatinine [（45.4±2.1）μmol/L vs.（94.3±4.7）μmol/L] and blood urea nitrogen [（5.96±0.28）mmol/L vs.（10.58±0.88）mmol/L] significantly increased,kidney weight [（156.67±4.97）g vs.（182.50±5.47）g] and area of kidney glomerulus [（3934±329） μm2 vs.（6586±347） μm2] significantly increased and extracellular matrix in glomerulus mesangial region [（21.0 ±1.5）% vs.（36.7±2.2）%] significantly increased in db/db DM mice.The serum creatinine（63.2±4.2）μmol/L,blood urea nitrogen（7.55±0.62）mmol/L,kidney weight（163.50±4.64）g,area of kidney glomerulus（4663±252）μm2 significantly（P〈0.05 all） improved in DM mice treated with everolimus.Conclusion：Everolimus can delay the progression of diabetic nephropathy.