摘要
目的:研究β-乳球蛋白(β-Lg)过敏小鼠肠道组织miR-155对肠道屏障功能、Th17细胞的影响。方法:选取清洁级健康BALB/c雌鼠建立β-Lg过敏小鼠模型并随机分为模型组、增强miR-155组、抑制miR-155组,每组各15只,选取健康BALB/c雌鼠作为空白组。空白组、模型组腹腔注射生理盐水;增强miR-155组腹腔注射miR-155增强剂;抑制miR-155组腹腔注射miR-155抑制剂。观察所有组别肠道组织(HE染色),检测血清D-乳酸、内毒素、二胺氧化酶(DAO)、白细胞介素-6(IL-6)、转化生长因子-β1(TGF-β1)、IL-21、超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)、Jarid2 mRNA、notch1 mRNA水平。结果:空白组小鼠结肠组织中未出现充血与炎性细胞浸润,模型组小鼠结肠组织中出现细胞损伤、炎性细胞浸润与充血,增强miR-155组小鼠结肠组织与模型组相比,细胞损伤、炎性细胞浸润与充血更严重,抑制miR-155组充血现象减少,炎性细胞浸润范围明显减少。与空白组相比,模型组、增强miR-155组、抑制miR-155组D-乳酸、内毒素、DAO、IL-6、IL-21水平升高,TGF-β1水平降低(P<0.05);与模型组、增强miR-155组相比,抑制miR-155组D-乳酸、内毒素、DAO、IL-6、IL-21水平降低,TGF-β1水平升高(P<0.05)。与空白组相比,模型组、增强miR-155组、抑制miR-155组的SOD水平、Jarid2 mRNA表达量降低,MPO水平、notch1mRNA表达量增高(P<0.05);与模型组、增强miR-155组相比,抑制miR-155组SOD水平、Jarid2 mRNA表达量升高,MPO水平、notch1 mRNA表达量降低(P<0.05)。结论:抑制miR-155对β-Lg过敏小鼠可改善肠道屏障功能,降低IL-6、IL-21水平,提高TGF-β1水平,通过调控Jarid2/notch1通路影响Th17细胞分化与功能。
Objective: To study the effect of intestinal tissue miR-155 of β-lactoglobulin(β-Lg) allergy mouse on intestinal barrier function and Th17 cells.Methods: The female BALB/c mice were selected to establish β-Lg allergy mice models, and randomly divided into model group, miR-155-enhanced group, and miR-155-inhibited group, with 15 mice in each group. The healthy mice were collected as the blank group. The blank group and model group were intraperitoneally injected normal saline, the miR-155-enhanced group and miR-155-inhibited group were intraperitoneally injected the miR-155 enhancer and the miR-155 inhibitor, respectively. Intestine HE staining, D-lactic acid, endotoxin, diamine oxidase(DAO), interleukin-6(IL-6), transforming growth factor-β1(TGF-β1), IL-21, superoxide dismutase(SOD), myeloperoxidase(MPO), Jarid2 mRNA, and notch1 mRNA levels in serum in all groups were determined and compared.Results: There were no hyperemia and inflammatory cell infiltration in the intestine tissue of mice in blank group. The cell damage, inflammatory cell infiltration and hyperemia occurred in the intestine tissue in model group. Compared with that respectively in model group, the epithelial injury, inflammatory cell infiltration, and congestion were more serious in miR-155-enhanced group. The congestion phenomenon was inhibited, and the range of inflammatory cell infiltration was significantly reduced in the miR-155-inhibited group. Compared with the blank group, D-lactic acid, endotoxin, DAO, IL-6, and IL-21 in model group, miR-155-enhanced group and miR-155-inhibited group increased, and the TGF-β1 decreased(all P<0. 05). Compared with that respectively in model group and miR-155-enhanced group, D-lactic acid, endotoxin, DAO, IL-6, IL-21 decreased, and TGF-β1 increased in miR-155-inhibited group(all P<0. 05). Compared with that respectively in blank group, the SOD and Jarid2 mRNA decreased, and MPO and notch1 mRNA increased in model group, miR-155-enhanced group, and miR-155 inhibited group(all P<0. 05). Compared with that respectively in model group and miR-155-enhanced group, the SOD and Jarid2 mRNA increased, MPO and notch1 decreased in the miR-155-inhibited group(P<0. 05).Conclusion: Inhibiting miR-155 in β-Lg-induced allergy can improve intestinal barrier function, reduce IL-6 and IL-21, increase TGF-β1, and affect Th17 cell differentiation and function by regulating Jarid2/notch1 pathway in mice.
作者
方拴锋
魏秀丽
王少雯
胡博
张煜
FANG Shuanfeng;WEI Xiuli;WANG Shaowen;HU Bo;ZHANG Yu(Dept.of Child Healthcare,Affiliated Children's Hospital of Zhengzhou University,Zhengzhou 450018,Henan,China;Dept.of Biochemistry and Molecular Biology,Xinxiang Medical University,Xinxiang 453003,Henan,China)
出处
《武汉大学学报（医学版）》
CAS
2021年第3期392-397,共6页
Medical Journal of Wuhan University
基金
河南省医学科技攻关计划项目(编号:2018020666)。
