白细胞介素-10对上皮-间质转化及内质网应激在肠纤维化中的影响  

Effects of interleukin-10 in epithelial-mesenchymal transition and endoplasmic reticulum stress on intestinal fibrosis

作　　者：欧洋肖[1] 陆允敏[1] 秦环龙[2] 陈红旗[2] 朱梅影[1] 陈维雄[1] 

机构地区：[1]上海交通大学附属上海市第六人民医院消化科,200233 [2]上海交通大学附属上海市第六人民医院普外科,200233

出　　处：《中华消化杂志》2012年第2期118-123,共6页Chinese Journal of Digestion

摘　　要：目的探讨白细胞介素（IL）-10对小鼠肠道纤维化及上皮一间质转化（EMT）的作用，以及该作用与内质网应激（ERS）的关系。方法42只IL-10。小鼠分为纤维化模型组（，2—18）、IL-10治疗组（n=12）和溶剂对照组（n=12），另取18只野生型小鼠作为阴性对照组。IL-10治疗组和溶剂对照组分别于第12周开始腹腔内注射IL-10和0．9％NaCl溶液，纤维化模型组和阴性对照组不予处理。采用HE染色及Masson胶原三色染色观察小鼠结肠组织损伤和纤维化变化，采用荧光定量PCR法检测小鼠结肠组织中胶原I、葡萄糖调节蛋白78（GRP78）、C／EBP同源蛋白（CHOP）、平滑肌肌动蛋白（α-SMA）、E-细胞钙黏蛋白（E—cad）mRNA的表达。采用定量免疫组织化学染色检测小鼠结肠组织中α—SMA和E-cad的表达。结果16周纤维化模型组、溶剂对照组结肠黏膜组织损伤评分（7．00±0．90和7．17±1．17）及胶原面积比[（17．78±4．15）％和（18．564-3．81）％]较阴性对照组[1．50±1．38和（9．11±2．99）％]和IL-10治疗组[4．33±0．82和（12．56±1．39）％]均明显升高（F=36．150，F=11．280；P=0．000）。12、14、16周纤维化模型组、溶剂对照组GRP78、α-SMA、胶原I表达量较同期阴性对照组均明显升高（均P〈0．05），E-cad表达量较阴性对照组明显降低（P〈0．05）。12周纤维化模型组CHOPmRNA表达量[（0．95±0．12）％]较阴性对照组[（0．21±0．12）％]明显升高（t=5．188，P=0．000），但在14、16周各组之间差异无统计学意义（P〉0．05）。14、16周IL-10治疗组GRP78、a-SMA、胶原I表达量[14周：（0．73±0．31）％，（1．18±0．11）％，（1．10±0．49）％；16周：（O．57土0．16）％，（O．81±0．50）％，（O．76±0．25）％]较纤维化模型组均明显降低（P〈O．05），E—cad表达量[14周：（O．73±0．29）％；16周：（0．97士0．25）％]较纤�Objective To investigate the effects of interleukin-10 on mice intestinal fibrosis and epithelial-mesenchymal transition （EMT）, and the relation between these effects and endoplasmic reticulum stress （ERS）. Methods Forty-two IL-10 knockout （IL-10-/-） mice were divided into fibrosis model group （n=18）, IL-10 treatment group （n= 12） and solvent control group （n= 12）,another 18 wild-type mice were taken as negative control group. IL-10 and 0. 9% NaC1 were intraperitonealy injected in IL-10 treatment group and solvent control group respectively since 12th week, and mice were sacrificed at week 14th and 16th, and no treatment to fibrosis model group and negative control group, The injury and fibrosis in mice colon tissue were detected with HE staining and Masson collagen staining. The expressions of collagen I , glucose-regulated protein78 （GRP78）, C/EBP homologous protein （CHOP） and a-smooth muscle actin （a-SMA） and E-cadherin （E-cad） at mRNA level were determined by realtime PCR. The expression of α-SMA and E-cad in mice colon tissue was examined by immunohistochemical staining. Results At 16th week, the colonic tissue injury scores （7. 004±0.90, 7. 17±1.17） and collagen area ratio （17.78%±4.15M,18.56%±3.81%） of fibrosis model group and solvent control group significantly increased compared with negative control group （1.50±1.38 and 9. 11%±2.99%） and IL-10 treatment qroup （4.33±0.82 and 12.56%± 1.39%） （F= 36. 150, F= 11. 280; P=0. 000）. At week 12th, 14th and 16th, the expressions of GRP78, α-SMA, collagen I in fibrosis model group and solvent control group significantly increased compared with negative control group （all P〈0.05）, however the expression of E-cad significantly decreased （P〈0.05）. The expression of CHOP mRNA in fibrosis model group （0.95% ±0. 12%） significantly increased compared with negative control group （0. 21% ±0. 12%） at week 12th （t = 5. 188,P=0. 000）, however there was no statistical significant dif

关 键 词：白细胞介素-10 纤维化 结肠 生物转化 上皮细胞 内质网 

分 类 号：R285.5[医药卫生—中药学]