摘要
目的观察血管紧张素转换酶抑制剂福辛普利(fosinopril,FOS)对脂多糖(lipopolysacchatide,LPS)诱导的大鼠肾小球系膜细胞(GMC)转化生长因子β1(TGF—β1)及β1整合素(Itg-β1)表达的影响。方法建立体外培养的大鼠GMC,鉴定后3~10代用于实验。实验分组:对照组、LPS刺激组(LPS组)、FOS干预组,根据LPS刺激基础上加FOS浓度不同又分为FOS高、中、低剂量组,分别为FOS1组、FOS2组、FOS3组。酶联免疫吸附试验测定6h、12h和24h细胞培养七清液中TGF-β1蛋白含量;荧光定量RT—PCR检测TGF—β1及Itg-β1 mRNA表达的变化。结果(1)大鼠GMC在6h、12h、24h三个时间点TGF—β蛋白分泌量(ng/L):对照组分别为958.55±34.67,1052.05±48.59,1166.06±35.39,LPS组分别为1342.12±39.87,1432.31±39.33,1537.77±43.79,各时间点均高于对照组(P均〈0.01),而FOS1组分别为779.58±48.64,878.33±29.50,962.57±31.94;FOS2组分别为989.311±73.56,1073.29±66.89,1210.75±61.68;FOS3组分别为1253.78±45.32,1348.18±45.81,1450.06±46.24,FOS各组TGF—β1蛋白分泌均低于LPS组(P均〈0.01);(2)大鼠GMC在6h、12h、24h三个时间点TGFβ1.mRNA表达量:LPS组均高于对照组;FOS1组、FOS2组、FOS3组均低于LPS组。(3)大鼠GMC在6h、12h、24h三个时间点Itg—β1 mRNA表达量:LPS组均高于照组;FOS1组、FOS2组、FOS3组均低于LPS组。结论LPS可诱导大鼠GMC TGF-β1蛋白分泌和mRNA表达增加,同时上调Itg—β1 mRNA表达,FOS可抑制LPS诱导的TGF—β1蛋白分泌和mRNA表达,同时下凋LPS诱导的Itg-β1 mRNA表达,提示FOS可以通过抑制细胞因子等非血流动力学机制对肾脏起保护作用。
Objective To observe the effects of one kind of angiotensin converting enzyme inhibitor (ACEI) drugs fosinopril (FOS) on transforming growth factor β1 (TGF-β1)and β1 - integrin( Itg-β1 )expression in rat glomerular mesangial cells ( GMC ) induced by lipopolysaechatide ( LPS ) . Methods We established the cultured glomerular mesangial cells of rat in vitro and passages 3 - 10 of cells were used in the experiment after identification. The experiment included the following groups: Control group, LPS induced group ( LPS group ) and FOS intervened group. According to the different concentrations of FOS, FOS intervened group was divided into high, middle and low dose FOS groups, which were FOS1 group, FOS2 group and FOS3 group respectively. The changes of TGF-β1 protein secretion was detected by the enzyme-linked immunosorbent-assay; The changes of TGF-β1 and Itg-β1 mRNA expression was detected by quantitative real-time RT-PCR. Results (1)TGF-β1 protein secretion in rat GMC at 6h, 12h, 24h three time points: They were 958.55 ±34. 67(ng/L) ,1 052. 05 ± 48.59(ng/L), 1 166. 06 ± 35.39 (ng/L) respectively in Control group. They were 1 342. 12 ± 39.87 (ng/L) , 1432. 31 ± 39.33 (ng/L) and 1537.77 ± 43.79 (ng/L) respectively in LPS group, which were higher significantly than those in Control group ( all P 〈 0. 01 ). They were 779. 58 ± 48.64 ( ng/L), 878.33 ± 29. 50 (ng/L) and 962.57±31.94(ng/L) in FOS1 group, 989.311±73.56(ng/L), 1073. 29 ± 66. 89 ( ng/L ) and 1210.75± 61.68 (ng/L) in FOS2 group, 1 253.78 ± 45.32 ( ng/L), 1 348. 18 ± 45.81 (ng/L) and 1 450. 06 ± 46. 24 ( ng/ L) in FOS3 group respectively,which were lower significantly in all FOS intervened groups than that in LPS group (all P 〈0. 01 ). (2)TGF-β1 mRNA expressions in rat GMC at 6h, 12h, 24h three time points were higher significantly than that in Control group. TGF-β1 mRNA expressions were lower significantly in all FOS int
出处
《国际儿科学杂志》
2011年第6期628-631,共4页
International Journal of Pediatrics
基金
基金项目:广东省医学科学技术研究基金项目(A2010450)
广州市医药卫生科技项目(2009-YB-028)
关键词
转化生长因子Β1
系膜细胞
福辛普利
Β1整合素
Transforming growth factor β1
Glomerular mesangial cell
Fosinopril
β1-integrin