脱氧胆酸溶液灌肠对大鼠内脏敏感性及脊髓c-fosmRNA表达的影响  

Rectal instillation of deoxycholic acid solution enhances visceral hypersensitivity and up-regulates c-fos mRNA expression in the spinal dorsal horn in rats

作　　者：王劲松[1] 余保平[1] 胡柳丹[1] 张丽静[1] 田亭亭[1] 

机构地区：[1]武汉大学人民医院消化内科,湖北省武汉市430060

出　　处：《世界华人消化杂志》2011年第25期2629-2636,共8页World Chinese Journal of Digestology

基　　金：中央高校基本科研业务费专项基金资助项目;No.20103020101000200~~

摘　　要：目的:研究脱氧胆酸溶液灌肠对大鼠结肠敏感性和脊髓背根神经节上c-fosmRNA表达的影响.方法:以脱氧胆酸溶液连续灌肠3d建立大鼠炎症后慢性内脏痛觉过敏模型,在灌肠前及灌肠后第1,2,3,4周采用结直肠扩张法(CRD)测定腹壁回撤反射(AWR)评分和内脏感觉压力阈值,然后处死大鼠,取出远端结肠组织,行髓过氧化物酶(MPO)测定、HE染色和肥大细胞计数,取脊髓背根神经节L5-S2用RT-PCR法测定c-fosmRNA的表达量.结果:灌肠后第1,2,3,4周,在20,40mmHg压力下,AWR评分实验组与对照组相比差异无统计学意义,而在60mmHg以上,实验组AWR评分均明显高于对照组(60mmHg:3.54±0.17vs3.31±0.23,3.58±0.17vs2.96±0.44,3.53±0.14vs3.07±0.30,3.60±0.13vs3.03±0.33,均P<0.05),且腹部抬起和骨盆抬起压力阈值实验组均低于对照组(P<0.05);灌肠后第2,3周,MPO值实验组高于对照组(0.39±0.12vs0.12±0.05,0.40±0.08vs0.12±0.05,均P<0.05),而第1,4周,两组间差异无统计学意义.灌肠后1w,实验组肥大细胞计数明显高于对照组(4.20±1.87vs1.10±0.74,P<0.05).在第1周,c-fosmRNA的表达量实验组明显高于对照组(0.74±0.04vs0.68±0.02,P<0.05).结论:DCA溶液反复灌肠诱导了大鼠短暂轻微的结肠炎症和持续稳定的内脏痛觉过敏,并且增加了脊髓背根神经节上c-fosmRNA的表达.DCA可能在某些肠易激综合征的痛觉过敏中发生作用.AIM： To investigate the effect of rectal instillation of deoxycholic acid solution （DAS） on colorectal visceral sensitivity and the expression of c-fos mRNA in the spinal dorsal horn in rats.METHODS： Rat models were established by giving a rectal perfusion of DSA for 3 days. Rectal distention test was performed to examine rectal sensitivity using AWR score and pressure threshold before and after treatment （1, 2, 3 and 4 wk）. The distal colon was used for myeloperoxidase （MPO） assay, and histological examination and mast cell counting were performed after treatment. L5-S2 dorsal root ganglia （DRG） were taken to examine the expression of c-fos mRNA by RT-PCR.RESULTS： The AWR score of the experiment group was increased in response to noxious intensities of CRD （60 mmHg） compared to the control group （1 wk： 3.54 ± 0.17 vs 3.31 ± 0.23, 2 wk： 3.58 ± 0.17 vs 2.96 ± 0.44, 3 wk： 3.53 ± 0.14 vs 3.07 ± 0.30, 4 wk： 3.60 ± 0.13 vs 3.03 ± 0.33, all P 〈 0.05）, but not to innocuous intensities. DCA treatment significantly decreased pressure threshold of visceral perception at each time point after rectal perfusion in both groups （all P 〈 0.05）. MPO activity was increased at weeks 2 and 3 （0.39 ± 0.12 vs 0.12 ± 0.05, 0.40 ± 0.08 vs 0.12 ± 0.05, both P 〈 0.05）, but not at week I and week 4. The levels of c-fos mRNA and mast cell number were significantly increased at week 1 in the experimental group compared to the control group （c-fos mRNA： 0.74 ± 0.04 vs 0.68 ± 0.02; mast cell number： 4.20 ± 1.87 vs 1.10 ± 0.74, both P 〈 0.05）.CONCLUSION： Repetitive colorectal instillation of DCA induces mild, transient colonic inflammation, results in persistent visceral hyperalgesia and referred pain, and increases spinal c-fos mRNA expression in rats.

关 键 词：脱氧胆酸 炎症后肠易激综合征 内脏高敏感 C-FOS 结直肠扩张 SD大鼠 

分 类 号：R574[医药卫生—消化系统]