PPAR-γ在三硝基苯磺酸诱导的肠纤维化模型小鼠结肠中的动态表达特点  

Dynamic expression characteristics of PPAR-γ in the colon of model mice with trinitrobenzenesulfonic acid-induced intestinal fibrosis

作　　者：成家飞[1] 徐艺[1] 顾培青[1] 朱磊[1] 曹婷婷[1] 张露[1] 李萍[1] 孙心 冯皖 沈洪[1] CHENG Jiafei;XU Yi;GU Peiqing;ZHU Lei;CAO Tingting;ZHANG Lu;LI Ping;SUN Xin;FENG Wan;SHEN Hong(The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210000, Jiangsu, China)

机构地区：[1]南京中医药大学附属医院,江苏南京210000

出　　处：《现代中西医结合杂志》2021年第34期3763-3768,3782,共7页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：国家自然科学基金青年项目(81704046,81704037)。

摘　　要：目的观察过氧化物酶体增殖物激活受体-γ(PPAR-γ)在小鼠肠纤维化模型中的动态表达及其与胶原的相关性。方法将90只BALB/c小鼠随机分为对照组和造模1周组、造模2周组、造模3周组、造模4周组、造模5周组、造模6周组、造模7周组、造模8周组,每组10只。对照组给予0.9%氯化钠溶液灌肠,造模各组采用多次三硝基苯磺酸(TNBS)灌肠诱导建立肠纤维化模型。对照组于灌肠8周结束、造模各组于相应时间点处死小鼠,测量小鼠结肠长度、结肠重量,HE染色和Masson染色观察小鼠结肠组织学形态,检测结肠组织中总胶原含量,Western blot和RT-PCR法分别测定小鼠结肠组织中PPAR-γ和Ⅰ型胶原α2(COL1A2)蛋白和mRNA表达水平。结果与对照组比较,造模6周组、造模7周组、造模8周组小鼠的结肠长度均明显缩短(P均<0.05),造模7周组、造模8周组小鼠的结肠重量均明显增加(P均<0.05),造模5周组、造模6周组、造模7周组、造模8周组结肠组织中总胶原含量均明显增高(P均<0.05)。从造模5周组开始,小鼠肠壁可见明显的炎症细胞浸润及胶原纤维增生;从造模1周组开始,PPAR-γ蛋白表达逐渐减少,COL1A2蛋白表达逐渐增加;从造模3周组开始,PPAR-γmRNA表达逐渐减少,COL1A2 mRNA表达逐渐增加。造模各组结肠组织中PPAR-γ和COL1A2蛋白及mRNA表达量均呈负相关(r=-0.949,P<0.05;r=-0.870,P<0.05)。结论TNBS灌肠诱导小鼠纤维化模型中,随造模时间延长,结肠组织中PPAR-γ表达逐渐减少,且PPAR-γ和COL1A2的表达呈负相关,PPAR-γ在肠纤维化进程中可能起重要作用。Objective It is to observe the dynamic expression of peroxisome proliferator-activated receptor-γ(PPAR-γ)in a mouse model of intestinal fibrosis and its correlation with collagen.Methods Ninety BALB/c mice were randomly divided into control group,1 week modeling group,2 week modeling group,3 week modeling group,4 week modeling group,5 week modeling group,6 week modeling group,7 week modeling group,8 week modeling group,10 animals in each group.The control group was given 0.9%sodium chloride solution by enema,and each modeling group was treated with trinitrobenzene sulfonic acid(TNBS)by enema for several times to induce intestinal fibrosis.The mice in the control group were sacrificed after 8 weeks of enema,the mice in each modeling group were sacrificed at the corresponding time point.The length and weight of the mouse colon were measured.The histological morphology of the mouse colon was observed by HE staining and Masson staining,and the total collagen content in the colon tissue was detected.The protein and mRNA expression levels of PPAR-γand type I collagenα2(COL1A2)in mouse colon tissues were respectively detected by Western blot and RT-PCR methods.Results Compared with the control group,the colon length of mice in the 6 week modeling group,7 week modeling group,and 8 week modeling group were significantly shortened(all P<0.05),the colon weight of mice in the 7 week modeling group and 8 week modeling group was significantly increased(all P<0.05),the total collagen content in the colon tissue of the 5 week modeling group,6 week modeling group,7 week modeling group,and 8 week modeling group were significantly increased(all P<0.05).Starting from the 5 week modeling group,obvious inflammatory cell infiltration and collagen fiber proliferation were found in the intestinal wall of the mice;starting from the 1 week modeling group,the expression of PPAR-γprotein gradually decreased,and the expression of COL1A2 protein gradually increased;starting from the 3 week modeling group,the expression of PPAR-γmRNA grad

关 键 词：肠纤维化 炎症性肠病 过氧化物酶体增殖物激活受体-Γ 三硝基苯磺酸 

分 类 号：R-332[医药卫生]