吗替麦考酚酯对阿霉素诱导的肾病幼鼠早期炎症反应的影响

Effect of mycophenolate mofetil on early inflammatory response in young rats with adriamycin-induced nephropathy

目的研究吗替麦考酚酯对阿霉素诱导的肾病幼鼠早期炎症反应的影响及机制。方法将SD幼鼠随机分为对照组、模型组及实验组,各18只。模型组和实验组通过尾静脉注射6.5 mg·kg^-1阿霉素构建肾病综合征模型,对照组给予等体积生理盐水,每天1次,连续给药14 d。建模成功后实验组灌胃10 mg·kg^-1吗替麦考酚酯,对照组及模型组灌胃等量生理盐水,每天1次,连续干预4周。用酶联免疫吸附法测定幼鼠血清中超敏C反应蛋白(hs-CRP)含量;以全自动生化分析仪检测血清肾功能指标水平。结果干预后4周,对照组、模型组和实验组幼鼠血清中hs-CRP分别为(0.33±0.10),(2.68±0.26),(1.32±0.06)mg·L^-1,幼鼠体重分别为(326.45±6.16),(205.16±3.48),(278.45±6.19)g,血清中肌酸酐(Cr)分别为(60.12±2.63),(145.16±2.39),(90.12±3.25)μmol·L^-1,尿素氮(BUN)分别为(8.69±2.31),(48.56±5.26),(22.15±3.45)mmol·L^-1,24 h尿蛋白分别为(1.26±0.15),(7.96±2.14),(5.02±1.03)μmol·L^-1;对照组和实验组分别与模型组比较,差异均有统计学意义(均P<0.05)。结论吗替麦考酚酯可降低肾病幼鼠机体炎性反应,通过下调肾组织中ICAM-1和VCAM-1蛋白表达进而发挥对幼鼠的肾保护作用。

Objective To investigate the effect and mechanism of mycophenolate mofetil on early inflammatory response in adriamycin-induced nephrotic rats.Methods SD young rats were randomly divided into control group,model group and test group,with 18 rats in each group.Nephrotic syndrome model was established by injecting 6.5 mg·kg^-1 adriamycin into tail vein in model group and test group.Control group was given equal volume of normal saline for 14 d.After successful modeling,test group was given mycophenolate mofetil 10 mg·kg^-1,while control group and model group were given the same amount of normal saline,once a day for 4 weeks.The serum levels of high-sensitivity C-reactive protein(hs-CRP)were measured by enzyme linked immunosorbent assay,the renal function was measured by automatic biochemical analyzer.Results Four weeks after the intervention,the serum hs-CRP levels in control group,model group and test group were(0.33±0.10),(2.68±0.26)and(1.32±0.06)mg·L^-1,the body mass of young rats were(326.45±6.16),(205.16±3.48)and(278.45±6.19)g,serum creatinine(Cr)were(60.12±2.63),(145.16±2.39)and(90.12±3.25)μmol·L^-1,urea nitrogen(BUN)were(8.69±2.31),(48.56±5.26)and(22.15±3.45)mmol·L^-1,24 h urine protein were(1.26±0.15),(7.96±2.14)and(5.02±1.03)μmol·L^-1.There were significant differences in control group and test group compared with model group(P<0.05).Conclusion Mycophenolate mofetil can reduce the inflammatory response of the kidney in young rats with nephropathy,and play a protective role in the kidney by down-regulating the expression of ICAM-1 and VCAM-1 in the kidney tissue.