西罗莫司延缓肾功能不全常染色体显性遗传性多囊肾病大鼠的疾病进程

Sirolimus slows down disease progression in rats with autosomal dominant polycystic kidney disease and renal dysfunction

目的:观察西罗莫司对已经出现肾功能不全的常染色体显性遗传性多囊肾病(ADPKD)大鼠疾病进程的影响。方法:20只6月龄ADPKD模型Han:SPRD杂合子(Cy/+)雄性大鼠,均已出现肾功能不全,随机分成实验组和对照组,每组10只。实验组按0.2 mg.kg-1.d-1的剂量每天灌胃西罗莫司口服液1次,对照组常规饲养,观察生存情况,定期测量大鼠体质量和血尿素氮(BUN)等指标,实验45 d后处死大鼠取双肾,测定双肾质量、双肾质量/体质量比(2K/TBW),免疫组化染色,统计增殖细胞核抗原(PCNA)阳性细胞数。结果:两组大鼠实验过程中均无死亡,体质量均增加,但两组间无显著差异;实验组与对照组BUN均进行性升高,但45 d实验组升高较对照组低12.5%(P<0.05);与对照组相比,实验组大鼠双肾质量、2K/TBW分别减少11.8%(P<0.05)和7.1%(P<0.01);实验组大鼠囊化程度较对照组轻,每个囊肿中PCNA阳性细胞数较对照组少(0.23±0.11vs0.47±0.24,P<0.05)。结论:西罗莫司口服液可以延缓已经发生肾功能不全的Han:SPRD大鼠肾功能减退的进程。

Objective：To investigate the influence of sirolimus on the disease progression of a rat model of autosomal dominant polycystic kidney disease （ADPKD）- Han ： SPRD with chronic renal insufficiency. Methods： Twenty 6-month-old male ADPKD heterozygous （Cy/±） rats with chronic renal insufficiency were divided into 2 groups at random （n= 10）. Rats in experimental group received intragastric administration of sirolimus （0.2 mg . kg^-1.d^-1 ） for 45 days and those in control group were bred routinely. The general state and renal function of rats were monitored throughout the treatment. The rats were sacrificed 45 days later and both kidneys were harvested, weighed; and the 2-kidney/total body weight （2K/TBW） ratio was determined. Then the kidneys were subjected to immunohistochemistry examination and the numbers of cells positive of proliferating cell nuclear antigen （PCNA） were counted. Results： There was no death in the 2 groups and all rats gained weights, with no significant difference between the 2 groups. Blood urea nitrogen （BUN） increased progressively in both groups, with the increase in experimental group lower than that in the control group by 12.5% on 45 days after administration （P〈0.05）. The 2- kidney-weight and 2K/TBW ratio in experimental group was lower by 11.8% （P〈0.05） and 7.1% （P〈0.01） than those in the control group, respectively. Renal enlargement and cystogenesis were inhibited by sirolimus, with the number of PCNA-positive cells per cyst being 0.23±0.11 in experimental group and 0.47±0.24 in the control group （P〈0.05）. Conclusion： Sirolimus can slow down the disease progression in Han ： SPRD rats with ADPKD, even though they had been in a condition of renal insufficiency.