结肠黏膜低度炎症对小鼠结肠PAR-2活化和内脏感觉过敏的诱发作用  

Low-grade mucosal inflammation induces colonic PAR-2 activation and visceral hypersensitivity in mice

作　　者：刘玮[1] 王承党[2] 

机构地区：[1]福建医科大学附属协和医院重症医学科,福建省福州市350001 [2]建医科大学附属第一医院消化内科,福建省福州市350005

出　　处：《世界华人消化杂志》2010年第32期3413-3419,共7页World Chinese Journal of Digestology

基　　金：福建省自然科学基金资助项目;No.2009J01138~~

摘　　要：目的:探讨结肠蛋白酶激活受体(PAR-2)活化与结肠黏膜低度炎症时小鼠内脏感觉过敏的关系.方法:36只C57B/6小鼠随机分为2组.A组(对照组),18只,给予无菌蒸馏水自由饮用;慢性低度炎症(LGI)组(S组),18只,1.5%葡聚糖硫酸钠(DSS)溶液自由饮用5d,续以无菌蒸馏水10d.第15天时观察病理学改变、测定腹壁肌电、免疫组织化学染色腰膨大部(L6-S1)脊髓背角SP、CGRP表达和结肠组织PAR-2表达.结果:第15天时,S组(LGI组)结肠黏膜炎症评分为1.500±0.926.结肠内压力为15mmHg时,S组的腹壁肌电幅值与A组比较无统计学意义(27.958μV±1.660μVvs26.947μV±0.854μV,P>0.05).当结肠内压力为30、45、60mmHg时,S组的腹壁肌电幅值均高于A组(33.455μV±3.786μVvs31.253μV±3.842μV;46.848μV±4.038μVvs37.267μV±2.542μV;47.207μV±18.151μVvs33.798μV±8.415μV,均P<0.05).S组结肠PAR-2和脊髓背角之SP、CGRPIA值均高于A组(40.769±8.422vs21.718±4.131;30.288±13.530vs10.788±4.490;46.829±26.261vs13.997±3.340,均P<0.05);PAR-2的IA值与SP、CGRPIA值之间都有正相关关系(r=0.622,P<0.05;r=0.588,P<0.05);SP、CGRP、PAR-2IA值与腹壁肌电幅值也都呈正相关(r=0.439-0.835,P<0.05).结论:结肠黏膜低度炎症可增加小鼠结肠的内脏敏感性,与结肠PAR-2的活化有关.AIM：To detect the expression of protease-activated receptor-2（PAR-2）in the colon and substance P（SP）and calcitonin gene-related peptide（CGRP）in the cornu dorsale medullae spinalis and to explore the relationship between the activation of PAR-2 and visceral hypersensitivity in mice with dextran sulfate sodium（DSS）-induced low-glade colonic mucosal inflammation（LGI）.METHODS：Thirty-six C57BL/6 mice were randomly divided into two groups：LGI group and control group.The LGI group was given 1.5% DSS solution for 5 d and distilled water for another 10 d,while the control group was given distilled water only.After treatment,the myoelectric activity of the abdominal wall at different levels of colorectal distension（CRD）was recorded.The expression of SP and CGRP in the cornu dorsale medullae spinalis and PAR-2 in the colonic mucosa was detected by immunohistochemistry.RESULTS：After treatment,colonic histological index（HI）in the LGI group was 1.500 ± 0.926.When the colon was distended to a pressure of 15 mmHg,the myoelectric activity of the abdominal wall in the LGI group was comparable to that in the control group（27.958 μV ± 1.660 μV vs 26.947 μV ± 0.854 μV,P 0.05）.However,the myoelectric activity of the abdominal wall was significantly higher in the LGI group than in the control group when the colon was distended to a pressure of 30,45 or 60 mmHg（33.455 μV ± 3.786 μV vs 31.253 μV ± 3.842 μV;46.848 μV ± 4.038 μV vs 37.267 μV ± 2.542 μV;47.207 μV ± 18.151 μV vs 33.798 μV ± 8.415 μV,all P 0.05）.The integrated optical density（IA）of PAR-2 staining in the distal colon was significantly higher in the LGI group than in the control group.The IA of SP and CGRP staining in the spine cord was also significantly higher in the LGI group than in the control group（40.769 ± 8.422 vs 21.718 ± 4.131;30.288 ± 13.530 vs 10.788 ± 4.490;46.829 ± 26.261 vs 13.997 ± 3.340,all P 0.05）.There is a positive correlation between the expression of PAR-2 and SP and between

关 键 词：肠易激综合征 结肠黏膜低度炎症 内脏感觉 蛋白酶活化受体-2 结肠扩张 P物质 降钙素基因相关肽 

分 类 号：R574.62[医药卫生—消化系统]