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-h everolimus group. Everolimus were given 2mg /kg ? d, eight weeks for corresponding 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 After experiment, blood samples were withdrawn from vena orbitalis posterior for biochemical analysis and kidneys of mice were used for histological analysis.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.%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搪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.
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