PPAR-γ激动剂抑制血管紧张素Ⅱ在增生性瘢痕成纤维细胞中的作用  

Effects of agonists of PPAR-γon angiotensin Ⅱ-induced proliferation and extracellular matrix synthesis in hypertrophic scar fibroblasts

作　　者：林康[1] 吕雷[1] 高伟阳[1] 何智灵[1] 张国佑[1] 

机构地区：[1]温州医学院附属第二医院手外科整形外科,温州325000

出　　处：《中华整形外科杂志》2013年第2期121-125,共5页Chinese Journal of Plastic Surgery

基　　金：国家自然科学基金资助项目（81171695）

摘　　要：目的研究过氧化物酶体增殖物激活受体γ（PPAR-γ）激动剂罗格列酮（rosiglitazone，Ros）抑制血管紧张素Ⅱ（angiotensinⅡ，AngⅡ）诱导的人增生性瘢痕成纤维细胞增殖、细胞外基质合成，并探讨其抗瘢痕的潜在作用。方法体外培养人增生性瘢痕成纤维细胞，在一定浓度的AngⅡ、Ros、GW9662作用下，采用CCK-8法、实时荧光定量RT-PCR和Western blot印迹法分别检测各组成纤维细胞增殖和细胞外基质（ECM）表达的情况。结果CCK-8法吸光度A值、Ⅰ型胶原蛋白（collagenⅠ，Col-Ⅰ）、纤维粘连蛋白（fibronectin，FN）mRNA以及蛋白表达，AngⅡ组分别为1．0825±0．007、6．45±0．97、4．92±0．86、2．92±0．41、2．78±1．04；Ros＋AngⅡ组为：0．7224±0．012、1．82±0．34、1．78±0．27、1．57±0．46、1．68±0．39。Ros组为：0．5547±0．012、0．97±0．12、1．07±1．08、1．05±0．43、1．14±0．36；GW9662＋Ros＋AngII组为：1．0560±0．005、5．83±0．24、4．47±0．32、2．69±0．35、2．62±0．27。CCK-8法吸光度，Col-Ⅰ和FNmRNA以及蛋白表达量，AngⅡ组与对照组比较，差异有统计学意义（P〈0．05），而Ros＋AngⅡ组则使这种效应明显降低（P〈0．05）。Ros组和对照组比较，差异无统计学意义（P〉0．05），GW9662＋Ros＋AngII组与Ros＋AngⅡ组比较，差异有统计学意义（P〈0．05）。结论PPAR-γ激动剂可有效抑制AngⅡ诱导的人增生性瘢痕成纤维细胞增殖及Col-Ⅰ和FN合成增多的效应，可能具有体外抗瘢痕纤维化的作用。Objective To study the effects of peroxisome prolilerator-activated receptor γ agonists on angiotensin Ⅱ -induced cellular response in cultured fibroblasts derived from patients with hypertrophic scars, so as to investigate its effects on preventing the formation of hypertrophic scars. Methods Fibroblasts were freshly isolated from hypertrophic scars and cultured with angioten Ⅱ , rosiglitazone and GW9662 at a certain concentration. Fibroblasts proliferation were assessed via Cell Counting Kit-8; the mRNA and protein expressions of Collagen Ⅰ and Fibronectin （FN） were determined by quantitative real- time RT-PCR and Western blotting. Results The absorbance of CCK-8 and relative expression of Collagen Ⅰ , FN mRNA and protein were 1. 082 5 ±0. 007,6.45 ± 0. 97,4.92 ± 0.86,2.92 ± 0.41,2.78 ± 1.04 in Ang Ⅱ group; 0.7224±0.012,1.82±0.34,1.78±0.27,1.57 ±0.46,1.68 ±0.39 in Ros ＋ Ang 11 group; 0. 554 7 ±0.012,0.97 ±0.12,1.07 ± 1.08,1.05 ±0.43,1. 14 ± 0.36 in Ros group; 1. 056 0 ± 0.005,5.83±0.24,4.47 ±0.32,2.69 ±0.35,2.62 ±0.27 in GW9662 ＋ ros ＋ Ang Ⅱ group. The results showed a significant difference between the Ang Ⅱ group and the control group（P 〈 0.05）. The effect of Ang Ⅱ could be markedly inhibited by Ros（P 〈 0.05）. In addition, Ros did not influence cell proliferation and production of extracellular matrix（P 〉 0.05）. There was a significant difference between the GW9662 ＋ Ros ＋ Ang Ⅱ group and the Ros ＋ Ang Ⅱ （P 〈 0.05）. Conclusions PPAR-γ agonists inhibit Ang Ⅱ -induced proliferation and extracellular matrix synthesis effectively in the hypertrophic scar fibroblasts. Thus PPAR-~ agonists may have potential therapeutic effect for hypertrophic scar.

关 键 词：增生性瘢痕 过氧化物酶体增殖物激活受体Γ 血管紧张素Ⅱ 成纤维细胞 

分 类 号：R622[医药卫生—整形外科]