阿利吉仑抑制转化生长因子-β_1诱导肾小管上皮细胞转分化的作用研究  

Effects of Aliskiren on transdifferentiation induced by TGF-β_1 in human renal tubular epithelial cells

作　　者：黄健[1] 陈松[1] 杨静[1] 闵亚丽[1] HUANG Jian;CHEN Song;YANG Jing;MIN Ya-li(Department of Nephrology,Guiyang First People＇s Hospital,Guiyang 550002,China)

机构地区：[1]贵阳市第一人民医院肾内科,贵阳550002

出　　处：《临床肾脏病杂志》2018年第8期466-470,共5页Journal Of Clinical Nephrology

摘　　要：目的探讨阿利吉仑对转化生长因子-β_1(TGF-β_1)诱导人近端肾小管上皮细胞(HKC)转分化的作用及其对血小板源性生长因子-BB(PDGF-BB)、血管内皮生长因子(VEGF)表达的影响。方法体外培养HKC,然后分为4组。阴性对照组HKC未做任何处理,阿利吉仑组HKC以阿利吉仑(1.0×10^(-7)mmol/L)单独处理24 h,TGF-β_1组HKC以TGF-β_1(8 ng/ml)单独处理24 h,研究组HKC以同一浓度的TGF-β_1加阿利吉仑共同处理24h。应用免疫细胞组织化学、逆转录-聚合酶链反应(RT-PCR)观察阿利吉仑对TGF-β_1诱导的HKC转分化的作用及对α-平滑肌肌动蛋白(α-SMA)、PDGF-BB、VEGF表达的影响。结果阴性对照组HKC有少量的PDGF-BB和α-SMA表达,有微量的VEGF表达。在TGF-β_1干预24 h后HKC有大量α-SMA、PDGF-BB的表达,与阴性对照组有显著差异(P<0.05);有少量的VEGF的表达,与阴性对照组无差异(P>0.05)。阿利吉仑单独作用于HKC 24 h后α-SMA、VEGF及PDGF-BB的表达与阴性对照组无显著差异(P>0.05)。TGF-β_1加阿利吉仑组比TGF-β_1组诱导的HKCα-SMA、PDGF-BB的表达明显降低(P<0.05),VEGF的表达无显著差异(P>0.05)。结论 TGF-β_1诱导肾小管上皮细胞转分化24 h可使PDGF-BB的表达明显增加,但对VEGF无明显改变。阿利吉仑对TGF-β_1诱导的肾小管上皮细胞转分化可能通过下调PDGF-BB的表达起抑制作用,但对VEGF的影响尚不明确,为阿利吉仑在肾间质纤维化的临床应用提供理论依据。Objective To explore Aliskiren on transdifferentiation of renal tubular epithelial cells（ H KC） induced by TGF-β1and to evaluate its effect on platelet derived growth factor（ PDGF-BB） 、vascular endothelialgrowth factor（ VEGF） expressing change. M ethods H KC were divided into four groups and cultured for 2 4 hours in different conditions separately ： Serum free as control,Treated with Aliskiren（ 1. 0 × 10^-7 m m ol/L）; Treated with TGF-β1 8 ng/ml）; Treated with TGF-β1plus Aliskiren in the sam e concentration. The expression ofα-SMA was assessed with RT-PCR,the expression of PDGF-BB、VEGF was assessed with RTPCR and im m unohistochem istry after 2 4 hours. Results There are little expression of PDGFBB,VEGF and α-SM A m RNA in control group. Com pared with the control group,The expression of PDGF-BB and α-SM A m RNA was m arkedly increased in H CK cultured with TGF-β1group（ P〈0.05）,which were suppressed significantly in H KC cultured with TGF-β1plus Aliskiren group（ P〈0.05）. but there are no significant changes in the expression of VEGFbetween different groups（ P〉0.05）. Conclusions Aliskiren may inhibit transdifferentiation of tubular epithelial cells induced by TGF-β1and reduce the expression of PDGF-BB. The inhibition of Aliskiren on transdifferentiation of tubular epithelial cells may be related to the down-regulation of PDGFBB. It is not very clear on the effect of the expression of VEGF.

关 键 词：阿利吉仑 转分化 血小板源性生长因子-BB 血管内皮生长因子 

分 类 号：R692[医药卫生—泌尿科学]