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

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
毛新妍;顾振纶;蒋小岗;侯燕;李梦姣;董丽霞
【期刊名称】《中国药理学通报》
【年(卷),期】2013(29)6
【摘要】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(Total 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-induced
pulmonary fibrosis 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-tratracheal 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 lung index and the levels of T-AOC and HYP were measured , 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 improved 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. 01 ); the alveolitis and fibrosis extent were attenuated significantly( P < 0. 05 or P < 0. 01 ); the levels of TGF-β, Smad2 , α-SMA , Collagen Ⅰ mRNA and protein were all decreased significantly ( P < 0. 05 or P < 0. 01 ) Conclusion DC can alleviate BLM-induced pulmonary fibrosis in mice through inhibiting TGF-β/Smad signaling pathway.
【总页数】6页(P818-823)
【作者】毛新妍;顾振纶;蒋小岗;侯燕;李梦姣;董丽霞
【作者单位】苏州中药研究所,江苏,苏州,215007;苏州大学药学院药理学系,江苏,苏州,215123;苏州中药研究所,江苏,苏州,215007;苏州大学药学院药理学系,江苏,苏州,215123;苏州中药研究所,江苏,苏州,215007;苏州大学药学院药理学系,江苏,苏州,215123;苏州中药研究所,江苏,苏州,215007;苏州中药研究所,江苏,苏州,215007;
苏州大学药学院药理学系,江苏,苏州,215123;苏州中药研究所,江苏,苏州,215007;苏州大学药学院药理学系,江苏,苏州,215123
【正文语种】中文
【中图分类】R-332;R284.1;R322.35;R563.130.22
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