缬沙坦抑制人类肾小管上皮细胞转分化的初步研究  

Inhibition of transdifferentiation of human renal tubular epithelial cells by valsartan

作　　者：文晓彦[1,2,3] 郑法雷[1,2,3] 孙阳中 李艳中 张晓明 

机构地区：[1]中国医学科学院,北京100730 [2]中国协和医科大学,北京100730 [3]北京协和医院肾内科,北京100730

出　　处：《中华肾脏病杂志》2000年第4期244-247,共4页Chinese Journal of Nephrology

基　　金：卫生部研究基金资助项目!(98-1-027)

摘　　要：目的　探讨血管紧张素ⅡⅠ型受体拮抗剂缬沙坦（ｖａｌｓａｒｔａｎ，Ｖａｌ）在人类肾小管上皮细胞系（ＨＫＣ）转分化中的作用。方法将培养的ＨＫＣ细胞分为（１）无血清培养对照组；（２）阳性对照组（ＭＣＰ－１＋ ＡＡＩ组）：培养液中加入马兜铃酸－Ｉ（ＡＡＩ）和单核细胞趋化蛋白－１（ＭＣＰ－１）；（３）Ｖａｌ组：培养液中加入Ｖａｌ；（４） ＭＣＰ－１＋ ＡＡＩ＋ Ｖａｌ组。应用间接酶标免疫组织化学方法（ＩＥＩ）检测 ＨＫＣ细胞α－平滑肌肌动蛋白（α－ＳＭＡ）、波形蛋白、角蛋白表达的变化，流式细胞技术检测α－ＳＭＡ阳性的ＨＫＣ细胞百分数。结果不同浓度缬沙坦（０．１、１０、１０ ０、１００． ０ ｐｇ／ｍｌ）分别作用于 ＨＫＣ细胞４８ｈ后，ＩＥＩ测定细胞角蛋白、波形蛋白及。ＳＭＡ抗原表达，与无血清对照组比无明显变化；流式细胞术测得Ｖａｌ组表达α－ＳＭＡ阳性的 ＨＫＣ细胞百分数分别为１０． ２％、５．６％、５．２％、０．９％，与无血清对照组（平均为３．１％）比较，差异无显著性意义（ Ｐ＞ ０．０５）。 ＭＣＰ－１＋ ＡＡＩ＋ Ｖａｌ（０．１、 １． ０、１０．０ ｐｇ／ｍｌ）组 ＨＫＣ细胞培养４８ｈ后，表达α－ＳＭＡ阳性的ＨＫＣ细胞分别为１７．?Objective To investigate the possible role of valsartan(Val) in transdifferentiation of human renal tubular epithelial cell line(HKC ). Methods HKC cells were divided into four groups: (1) serum-free (negative control); (2) MCP-1 + AAI-treated (positive control); (3) Val-treated alone; (4) Val-inhibition(treated with MCP-1 + AAI + Val). Then the expression of vimentin, α-smooth muscle actin (α-SMA ) of HKC cells were assessed by indirect enzyme immunohistochemistry (IEI), and the percentage of α-SMA(+ ) HKC cells was assessed by flow cytometry. Results No difference in expressions of vimentin and α-SMA by IEI and the percentage of α-SMA(+ ) HKC cells by cytometry were found between serum-free control HKC cells and Val treated ones. The expressions of vimentin and α-SMA in positive controls were markedly stronger than negative controls; while these expressions in Val + MCP-1 + AAI-treated HKC cells were less strong than those in positive controls. The percentage of α-SMA(+ ) HKC cells in the positive controls was significantly higher than that in negative controls(91. 8% vs 3. 1%, P < 0. 05), while the percentages of α-SMA(+ ) HKC cells in MCP-1 + AAI + Val group at Val doses of 0. 1, 1. 0, 10. 0 pg/ml (17. 3%, 32. 4%, 10. 0% )were dramatically lower than that in positive controls(P < 0. 005 ). Conclusions (1 ) No influence of valsartan on transdifferentiation of normal HKC cells in vitro was found in this study. (2) Valsartan may inhibit the transdifferentiation of HKC cells induced by synergistic effect of MCP-1 and AAI in vitro.

关 键 词：肾小管上皮细胞转分化 缬沙坦 肾间质纤维化 

分 类 号：R965[医药卫生—药理学]