结肠粘膜低度炎症诱发小鼠结肠PAR-2活化和内脏感觉过敏
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摘要
目的:
测定结肠粘膜低度炎症时小鼠内脏感觉和结肠蛋白酶激活受体(PAR-2)、脊髓背角神经递质(P物质、降钙素基因相关肽)的变化,探讨PAR-2活化与内脏感觉过敏的关系。
方法:
36只C57B/6小鼠随机分为2组,即:(1)A组,对照组,18只,给予无菌蒸馏水自由饮用;(2)S组,慢性低度炎症组(LGI组),18只,1.5%葡聚糖硫酸钠(DSS)溶液自由饮用5天,续以无菌蒸馏水10天。第15天时观察病理学改变、测定腹壁肌电、免疫组化染色腰膨大部(L6-S1)脊髓背角SP、CGRP表达,及结肠组织PAR-2表达。
结果:
第15天时,S组(LGI组)结肠粘膜炎症评分为1.500±0.926。结肠内压力为15mmHg时S组的腹壁肌电幅值(27.958±1.660μV)与A组(26.947±0.854μV, P>0.05)比较无统计学意义。当结肠内压力为30mmHg、45 mmHg、60mmHg时S组的腹壁肌电幅值(33.455±3.786,46.848±4.038 , 47.207±18.151μV )均高于A组(31.253±3.842 ,37.267±2.542,33.798±8.415,P均﹤0.05)。S组结肠的PAR-2(40.769±8.422)和脊髓背角SP(30.288±13.530)、CGRP(46.829±26.261)IOD值均高于A组(PAR-2 21.718±4.131,SP 10.788±4.490,CGRP 13.997±3.340, P均<0.05);PAR-2的IOD值与SP、CGRP IOD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-2 IOD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,与结肠蛋白酶活化受体-2的活化有关。
Objective:
To investigate the expressions of protease-activated receptor-2(PAR-2) in colonic tissue, substance P(SP) and calcitonin gene-related peptide(CGRP) in cornu dorsale medullae spinalis, and then to explore the relationship between the activation of PAR-2 and visceral hypersensitivity in mice with DSS-induced low glade colonic mucosal imflammation.
Methods:
Thirty-six C57BL/6 mice were randomly divided into two groups: low grade inflammation group(group S, LGI) and control group (group A). The mice in group S were given 1.5%DSS solution for 7 days, and then distilled water for another 10 days, while the mice in group A were treated with distilled water only. The abdominal myoelectric activities(AMAs) at different levels of colorectal distension(CRD) were recorded in the 15th day.The expression of substance P(SP), calcitonin gene-related peptide(CGRP) in spine cord and the changes of PAR-2 in the colonic mucosa were detected by immunohistochemistry after CRD.
Results:
In the 15th, the HI in group S was 1.500±0.926. When colon distention by 15mmHg,the AMAs (27.958±1.660μV) in group S were similar to that in group A (26.947±0.854μV, P>0.05). The AMAs in group S with colonic distention by 30mmHg、45 mmHg、60mmHg were 33.455±3.786, 46.848±4.038,and 47.207±18.151 (μv) respectively, and which were significantly higher than those in group A (31.253±3.842,37.267±2.542,and 33.798±8.415(μv) (P<0.05, respectively). The integrated optical density(IOD) of PAR-2 in the distal colon(40.769±8.422) was highter than that in group A(21.718±4.131). And the IODs of SP (30.288±13.530) and CGRP (46.829±26.261) in spine cord in group were significantly higher than those in group A (SP 10.788±4.490,CGRP 13.997±3.340)(P﹤0.05 respectively). There was a positive relationship between the expression of PAR-2 and SP, or between the expression of PAR-2 and CGRP in group S (r=0.622、P<0.05, r=0.588、P<0.05). The expression of PAR-2、SP,or CGRP was a close correlation with AMAs in group S (r = 0.439-0.835, P <0.05).
Conclusion:
Low grade mucosal inflammation activated visceral hypersensitivity in mice, PAR-2 maybe involved its mechanisms.
测定结肠粘膜低度炎症时小鼠内脏感觉和结肠蛋白酶激活受体(PAR-2)、脊髓背角神经递质(P物质、降钙素基因相关肽)的变化,探讨PAR-2活化与内脏感觉过敏的关系。
方法:
36只C57B/6小鼠随机分为2组,即:(1)A组,对照组,18只,给予无菌蒸馏水自由饮用;(2)S组,慢性低度炎症组(LGI组),18只,1.5%葡聚糖硫酸钠(DSS)溶液自由饮用5天,续以无菌蒸馏水10天。第15天时观察病理学改变、测定腹壁肌电、免疫组化染色腰膨大部(L6-S1)脊髓背角SP、CGRP表达,及结肠组织PAR-2表达。
结果:
第15天时,S组(LGI组)结肠粘膜炎症评分为1.500±0.926。结肠内压力为15mmHg时S组的腹壁肌电幅值(27.958±1.660μV)与A组(26.947±0.854μV, P>0.05)比较无统计学意义。当结肠内压力为30mmHg、45 mmHg、60mmHg时S组的腹壁肌电幅值(33.455±3.786,46.848±4.038 , 47.207±18.151μV )均高于A组(31.253±3.842 ,37.267±2.542,33.798±8.415,P均﹤0.05)。S组结肠的PAR-2(40.769±8.422)和脊髓背角SP(30.288±13.530)、CGRP(46.829±26.261)IOD值均高于A组(PAR-2 21.718±4.131,SP 10.788±4.490,CGRP 13.997±3.340, P均<0.05);PAR-2的IOD值与SP、CGRP IOD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-2 IOD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,与结肠蛋白酶活化受体-2的活化有关。
Objective:
To investigate the expressions of protease-activated receptor-2(PAR-2) in colonic tissue, substance P(SP) and calcitonin gene-related peptide(CGRP) in cornu dorsale medullae spinalis, and then to explore the relationship between the activation of PAR-2 and visceral hypersensitivity in mice with DSS-induced low glade colonic mucosal imflammation.
Methods:
Thirty-six C57BL/6 mice were randomly divided into two groups: low grade inflammation group(group S, LGI) and control group (group A). The mice in group S were given 1.5%DSS solution for 7 days, and then distilled water for another 10 days, while the mice in group A were treated with distilled water only. The abdominal myoelectric activities(AMAs) at different levels of colorectal distension(CRD) were recorded in the 15th day.The expression of substance P(SP), calcitonin gene-related peptide(CGRP) in spine cord and the changes of PAR-2 in the colonic mucosa were detected by immunohistochemistry after CRD.
Results:
In the 15th, the HI in group S was 1.500±0.926. When colon distention by 15mmHg,the AMAs (27.958±1.660μV) in group S were similar to that in group A (26.947±0.854μV, P>0.05). The AMAs in group S with colonic distention by 30mmHg、45 mmHg、60mmHg were 33.455±3.786, 46.848±4.038,and 47.207±18.151 (μv) respectively, and which were significantly higher than those in group A (31.253±3.842,37.267±2.542,and 33.798±8.415(μv) (P<0.05, respectively). The integrated optical density(IOD) of PAR-2 in the distal colon(40.769±8.422) was highter than that in group A(21.718±4.131). And the IODs of SP (30.288±13.530) and CGRP (46.829±26.261) in spine cord in group were significantly higher than those in group A (SP 10.788±4.490,CGRP 13.997±3.340)(P﹤0.05 respectively). There was a positive relationship between the expression of PAR-2 and SP, or between the expression of PAR-2 and CGRP in group S (r=0.622、P<0.05, r=0.588、P<0.05). The expression of PAR-2、SP,or CGRP was a close correlation with AMAs in group S (r = 0.439-0.835, P <0.05).
Conclusion:
Low grade mucosal inflammation activated visceral hypersensitivity in mice, PAR-2 maybe involved its mechanisms.
引文
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