规律有氧运动促进梗阻性黄疸小鼠肠黏膜紧密连接蛋白Claudin-1的表达及激活C型鸟苷酸环化酶通路有利于损伤的修复

张宇 毛海峰 彭瑞

解剖学报 ›› 2020, Vol. 51 ›› Issue (4) : 588-594.

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解剖学报 ›› 2020, Vol. 51 ›› Issue (4) : 588-594. DOI: 10.16098/j.issn.0529-1356.2020.04.020
组织学胚胎学发育生物学

规律有氧运动促进梗阻性黄疸小鼠肠黏膜紧密连接蛋白Claudin-1的表达及激活C型鸟苷酸环化酶通路有利于损伤的修复

  • 张宇 毛海峰 彭瑞*
作者信息 +

Regular aerobic exercise increasing the expression intestinal mucosal tight junction protein claudin-1 and activating GC-C pathway in facilitating the recovery of obstructive jaundice in mice

  • ZHANG Yu MAO Hai-feng PENG Rui*
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文章历史 +

摘要

目的 探讨规律有氧运动对梗阻性黄疸小鼠肠黏膜紧密连接蛋白Claudin-1的影响,及C型鸟苷酸环化酶(GC-C)通路在肠黏膜屏障功能与炎症反应中的作用机制。  方法 取30只雄性昆明小鼠构建梗阻性黄疸模型,随机分成规律有氧运动组(EX)和模型组(M),另设空白组(SO),每组15只。采用一般情况观察,ELISA技术,HE染色,肠组织相关因子免疫组织化学染色,蛋白检测及Real-time PCR技术,研究规律有氧运动的改善作用机制。  结果 M组腹部、尾部黄染严重,出现黄尿及粪便呈浅灰色,开腹可见胆管悬挂处呈囊性扩张。血清中总胆红素(TBIL)、总胆汁酸(TBA)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)及炎性因子白细胞介素-8(IL-8)、肿瘤坏死因子(TNF)-α蛋白含量显著升高。相比M组,EX组上述蛋白含量显著下降(P<0.01),光学显微镜下显示,M组肝索排列紊乱,且出现空泡、核裂症及大量水泡;肠组织绒毛稀疏且高度不均,肠腺、肌层消失或萎缩,间质层水肿且炎性细胞浸润。与M组相比,EX组肠黏膜增厚,绒毛数量相比M组明显增多,间质出现轻度水肿。与M组相比,EX组肠组织Claudin-1、GC-C、鸟苷蛋白(Gn)、尿鸟苷素(Ugn)及环磷酸鸟苷(cGMP)蛋白表达及蛋白含量和基因表达明显上升(P<0.01)。  结论 规律有氧运动能有效促进肠黏膜紧密连接蛋白Claudin-1的表达,激活GC-C通路,减轻肠黏膜屏障功能受损及炎症反应。

Abstract

Objective To investigate the effect of regular aerobic exercise on intestinal mucosal tight junction protein claudin-1 in obstructive jaundice mice and the mechanism of guanylate cyclase C (GC-C) pathway in intestinal mucosal barrier function and inflammatory response.   Methods Thirty male Kunming mice were used to establish the obstructive jaundice model and then were randomly divided into 2 groups: regular aerobic exercise group (EX) and model group (M). In addition, the blank group was set up, 15 mice in each group. ELISA, HE staining, intestinal tissue-associated factor immunohistochemical staining, protein detection, Real-time PCR were used in present study in order to explore the effect of the regular aerobic exercise on the obstructive jaundice of the intestinal mucosal.   Results Yellow discoloration of skin in both abdomen and tail was found in mice in M group. The urine color changed into deep yellow and feces appeared light gray.The bile showed cystic dilatation. Serum total bilirubin (TBIL), total bile acid (TBA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and inflammatory factors interleukin (IL)-8, tumor necrosis factor (TNF)-α protein content significantly elevated. Compared with the M group, the protein content of each indicator in the EX group decreased significantly (P<0.01).Microscopically, the hepatic cord arrangement was disordered in group M, and vacuoles, mitosis, and degeneration appeared in large numbers. The intestinal tissue was sparse and uneven, the intestinal gland and muscle layer disappeared or atrophied, and the interstitial layer was edema and inflammatory cells infiltrated. In the EX group, the intestinal mucosa was thickened, and the number of villi significantly increased compared with the M group and the interstitial showed mild edema. Compared with group M, the positive expression, protein content and gene expression of claudin-1, GC-C, guanylin (Gn), uroguanylin (Ugn) and cyclic guanosine monophosphate (cGMP) in EN group increased significantly (P<0.01).   Conclusion Regular aerobic exercise can effectively promote the expression of tight junction protein Claudin-1 in intestinal mucosa, and activate GC-C pathway to reduce the damages of intestinal mucosal barrier function and inflammatory response. 

关键词

规律有氧运动 / 肠黏膜屏障 / 紧密连接蛋白 / C型鸟苷酸环化酶通路 / 胆管悬挂法 / 免疫组织化学 / 实时定量聚合酶链反应 / 小鼠

Key words

Regular aerobic exercise / Intestinal mucosal barrier / Tight junction protein / Guanylate cyclase C pathway / Bile duct suspension / Immunohistochemistry / Real-time PCR / Mouse

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张宇 毛海峰 彭瑞. 规律有氧运动促进梗阻性黄疸小鼠肠黏膜紧密连接蛋白Claudin-1的表达及激活C型鸟苷酸环化酶通路有利于损伤的修复[J]. 解剖学报. 2020, 51(4): 588-594 https://doi.org/10.16098/j.issn.0529-1356.2020.04.020
ZHANG Yu MAO Hai-feng PENG Rui. Regular aerobic exercise increasing the expression intestinal mucosal tight junction protein claudin-1 and activating GC-C pathway in facilitating the recovery of obstructive jaundice in mice[J]. Acta Anatomica Sinica. 2020, 51(4): 588-594 https://doi.org/10.16098/j.issn.0529-1356.2020.04.020
中图分类号: G806    Q95-33    

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基金

江西省教育厅科学技术研究项目;江西省卫计委科技计划项目

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