西罗莫司和环孢素对常染色体隐性遗传性多囊肾病大鼠疾病进展过程的影响

摘要

目的 观察西罗莫司和环孢素(cyclosporin,CsA)对常染色体隐性遗传性多囊肾病(autosomal recessive polycystic kidney disease,ARPKD) 大鼠疾病进程的影响. 方法 20只4周龄ARPKD模型PCK大鼠,雌雄各半,采用成组设计随机分为西罗莫司组(n=6)、环孢素组(n=8)和对照组(n=6),分别每天以西罗莫司稀释液、环孢素稀释液和无药物的饮用水灌胃,每周测体重,分别于4、6、8、10周龄内眦静脉取血监测肾功能,分别在4、8、12周龄行双肾超声观察囊肿数量及大小,12周龄时全部处死,取双肾称重,并行切片HE染色观察囊肿体积密度(cyst volume density,CVD). 结果 3组大鼠实验过程中均无死亡,体重均增加,但3组间无显著差异(P>0.05).12周龄时西罗莫司组超声下肾脏体积、肾脏内囊肿数和最大囊肿最大截面面积均明显低于对照组[(1.65±0.25)cm3 vs.(2.00±0.36) m3,q=3.426,P<0.05;(31.75±6.57)个 vs.(43.08±10.28)个,q=3.638,P<0.05;(0.0828±0.0420)cm2 vs.(0.1373±0.0536)cm2,q=3.966,P<0.05];环孢素组超声下肾脏体积、肾脏内囊肿数和最大囊肿最大截面面积与对照组无显著差异(P>0.05).西罗莫司组、环孢素组和对照组在双肾质量、双肾质量/体重比(2-kidney/total body weight ratio,2K/TBW)、10周龄时血清BUN和Cr以及CVD均无显著差异(P>0.05).结论 西罗莫司和CsA对PKD大鼠疾病的进程未表现出明显的影响.%Objective To observe the effects of sirolimus and cyclosporine in the progression of autosomal recessive polycystic kidney disease (ARPKD) in an orthologous animal model of human ARPKD, the PCK rats.Methods Four-week-old PCK rats (n=20), sex in half, were randomly divided into control group (drug free drinking water, n=6), sirolimus group (n=6), and cyclosporine group (n=8), respectively.They were given daily gavage with drinking water, sirolimus dilution, or cyclosporine dilution.The body weight was measured every week.The renal function was monitored throughout the treatment periods at 4, 6, 8, and 10 weeks.The kidney volume, number of cysts and maximum area of the largest cyst under ultrasound were measured at 4, 8, and 12 weeks.The kidneys were harvested, weighed, and analyzed histologically (cyst volume density, CVD) at 12 weeks.ResultsNone of the PCK rats died during the study.The body weight was increased in all the rats, witnout significant difference among the 3 groups (P>0.05).At 12 weeks, the kidney volume (cm3), number of cysts and maximum area of the largest cyst (cm2) under ultrasound were reduced significantly in the sirolimus group than the control group [(1.65±0.25) cm3 vs.(2.00±0.36) cm3, q=3.426, P<0.05;31.75±6.57 vs.43.08±10.28, q=3.638, P<0.05;(0.0828±0.0420) cm2 vs.(0.1373±0.0536) cm2, q=3.966, P<0.05].There were no significant differences between cyclosporine group and control group on kidney volume, number of cysts and maximum area of the largest cyst under ultrasound (P>0.05).The sirolimus group, cyclosporine group and control group showed no significant difference in kidney weight, 2-kidney/total body weight ratio (2K/TBW), serum BUN and Cr, and CVD at 10 weeks (P>0.05).Conclusion Sirolimus and cyclosporine showed no significant effects on the disease process of PKD rats.