吲哚-3-原醇对博莱霉素所致小鼠肺纤维化的干预作用及其机制

Effect of indole-3-carbinol on bleomycin-induced pulmonary fibrosis in mice and its mechanisms

目的观察吲哚-3-原醇(indole-3-carbinol,I3C)对博莱霉素致小鼠肺纤维化的干预作用并初步探讨其机制。方法Imprinting Control Region(ICR)小鼠随机分为6组:正常组、模型组、醋酸泼尼松组(6.67 mg.kg-1)、吲哚-3-原醇小、中、大剂量组(25、50、100 mg.kg-1)。小鼠气管内注射博莱霉素制备肺纤维化模型后,第2天给予相应药物,每天1次。连续给药28 d后处死小鼠检测其肺系数、血清和肺组织羟脯氨酸(Hydroxyproline,HYP)、血清总抗氧化能力(To-tal antioxidative capacity,T-AOC);取固定部位肺组织切片HE染色,进行病理学观察;RT-PCR法检测肺组织中α-SMA、CollagenⅠ、TGF-β、Smad2 mRNA的表达;Western blot法检测肺组织中α-SMA、TGF-β、Smad2蛋白的表达。结果吲哚-3-原醇能够提高小鼠血清的总抗氧化能力(P<0.05或P<0.01),同时可以降低肺系数和肺组织中的HYP含量(P<0.05或P<0.01);光镜观察表明吲哚-3-原醇能明显减轻肺纤维化小鼠肺泡炎和肺纤维化程度(P<0.05或P<0.01);RT-PCR检测发现吲哚-3-原醇能明显降低肺组织α-SMA、CollagenⅠ、TGF-β、Smad2基因表达水平(P<0.05或P<0.01);Western blot分析结果说明吲哚-3-原醇能明显降低肺组织α-SMA、TGF-β、Smad2蛋白表达(P<0.05或P<0.01)。结论吲哚-3-原醇可能通过抑制TGF-β/Smad信号通路来减轻博莱霉素致小鼠肺纤维化。

Aim To investigate the effects of indole-3- carbinol （13 C） on bleomycin-indueed pulmonary fibro- sis in mice. Methods The mice were divided into six groups randomly ： nomal group, model group, predniso- lone group and 13C low-dose, middle-dose, high-dose group. Pulmonary fibrosis model was replicated by in- tratraeheal injection of bleomycin. In the next day, the mice were treated by intragastric administration once a day. After 28 days, the mice were sacrificed. The lungindex and the levels of T-AOC and HYP were meas- ured, and the pathologic changes of the lung tissue were obtained by HE staining. The levels of TGF-β Smad2, α-SMA, Collagen I mRNA were assayed by RT-PCR. The levels of TGF-β,Smad2, α-SMA protein were analyzed by Western blot. Results 13C im- proved the activity of T-AOC in serum and reduced pulmonary index and the content of HYP as well （P 〈 0. 0 5 or P 〈 0. 0 1 ） ; the alveolitis and fibrosis extentwere attenuated significantly（ P 〈 0. 05 or P 〈 0.01 ） ; the levels of TGF-β, Smad2, α-SMA, Collagen Ⅰ mR- NA and protein were all decreased significantly （P 〈 0.05 or P 〈 0. 01 ） Conclusion 13C can alleviateBLM-induced pulmonary fibrosis in mice through inhib- iting TGF-β/Smad signaling pathway.