慢性吸入鹅脱氧胆酸致肺纤维化大鼠模型的时相研究  

Profibrotic effects of chronic aspiration of chenodeoxycholic acid in rats at different stages

作　　者：刘亚南 张毛为 朱洁晨 赵玲 季磊 朱述阳 陈碧 陈昊 LIU Yanan;ZHANG Maowei;ZHU Jiechen;ZHAO Ling;JI Lei;ZHU Shuyang;CHEN Bi;CHEN Hao(Department of Respiratory Medicine,the Affiliated Hospital of Xuzhou Medical College,Xuzhou,Jiangsu 221002,China)

机构地区：[1]徐州医科大学附属医院呼吸与危重症医学科,江苏徐州221002

出　　处：《徐州医科大学学报》2021年第7期509-514,共6页Journal of Xuzhou Medical University

基　　金：国家自然科学基金青年科学基金(81600044);江苏省“六大人才高峰”高层次人才(WSN-081);徐州市科技计划(KC16SH079)。

摘　　要：目的探讨慢性吸入鹅脱氧胆酸(CDCA)大鼠模型中的致纤维化效应在不同时相的变化及其机制。方法气管内多次微量给予CDCA建立肺纤维化大鼠模型,以0.5‰二甲基亚砜(DMSO)作为对照。在造模第2、4、6、8周检测CDCA在不同时期的致肺纤维化作用。结果与对照组相比,CDCA造模组大鼠第2周可见错乱分布的肺泡结构,炎性细胞在肺泡腔内浸润;第6周炎性渗出较第4周明显减少,大量成纤维细胞增殖、肺纤维化瘢痕形成。Masson染色示,肺间质的胶原纤维在造模第2、4、6、8周时蓝染的面积逐渐增大。在第6周后,CDCA组的炎症评分及纤维化评分都明显增加(P<0.05)。肺组织α-平滑肌肌动蛋白(α-SMA)、羟脯氨酸(HYP)含量显著增加,转化生长因子β1(TGF-β1)、基质金属蛋白酶-9(MMP-9)表达上调,丙二醛(MDA)含量呈递增趋势,超氧化物歧化酶(SOD)活性呈递减趋势(P<0.05)。结论慢性吸入CDCA大鼠模型构建成功;第6周以后肺纤维化最明显,其机制可能与TGF-β1/氧化应激有关。Objective To explore the profibrotic effects of chronic aspiration of chenodeoxycholic acid(CDCA)in rats and underlying mechanisms.Methods A rat model of pulmonary fibrosis was established by multiple intratracheal injection of CDCA.Rats treated with 0.5‰DMSO were set as a control group.On Weeks 2,4,6 and 8,the profibrotic effects of CDCA were assessed at different stages.Results Compared with the control group,rats in the CDCA modeling group showed disordered alveolar structure and inflammatory cell infiltration in the alveolar space on Week 2.Compared with those on Week 4,inflammatory infiltration significantly relieved on Week 6,with proliferation of plenty of fibroblasts and the formation of pulmonary fibrosis scars.According to Masson staining,the blue area of collagen fibers in the interstitium remarkably increased on Weeks 2,4,6,and 8.After Week 6,the scores of inflammation and fibrosis obviously increased in the CDCA group than those in the control groups(P<0.05).The levels ofα-smooth muscle actin(α-SMA),hydroxyproline(HYP),transforming growth factor-β1(TGF-β1),and matrix metallopeptidase-9(MMP-9)were remarkably up-regulated after Week 6 in rat lungs in the CDCA group,while the content of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)were gradually down-regulated compared with those in the control group(P<0.05).Conclusions The rat model of chronic aspiration of CDCA is successfully established,with pulmonary fibrosis is most obviously after Week 6,which may be associated with the TGF-β1-ROS pathway.

关 键 词：特发性肺纤维化 鹅脱氧胆酸 转化生长因子-Β1 氧化应激 

分 类 号：RR364.33[医药卫生—呼吸系统] R563.9[医药卫生—内科学]