蛋白酶激活受体2在肠易激综合征患者内脏敏感性中的作用
The role of protease activated receptor 2 in visceral sensitivity of irritable bowel syndrome patients

摘要：目的 通过观察肠易激综合征(IBS)患者直肠蛋白酶激活受体2(PAR2)的表达情况，同时观察外源性的PAR2对内脏敏感性的影响，了解PAR2在IBS患者内脏敏感性中的作用。方法 按照罗马Ⅲ标准选取本院住院及门诊便秘型IBS(IBS-C)患者16例、腹泻型IBS(IBS-D)患者18例，对照组18例，经结肠镜钳取直肠黏膜组织，采用免疫组化和实时荧光定量PCR法观察PAR2的表达情况。在正常大鼠直肠内注入PAR2激动剂，观察内脏敏感性的改变。结果 PAR2主要表达于直肠黏膜上皮细胞，绒毛中可见大量的表达，此外在黏膜下层也可见阳性表达。通过图像分析，各组的积分吸光度(IA)没有明显的差异，PAR2在IBS直肠黏膜组织中mRNA表达水平也没有统计学差异。在大鼠直肠内注入PAR2激动剂(SLIGRL-NH2，50μg/只)4h后，测定腹壁肌电活动,发现PAR2激动剂组在直肠球囊扩张时，随着扩张球囊容量增加，腹壁肌肉收缩的肌电图明显增加，球囊无扩张时腹壁外肌通常无肌电活动。球囊容量增加到0.8mL、1.0mL和1.2mL时PAR2激动剂组的腹壁肌电活动，与对照组相比，差异有统计学意义(P<0.01)。结论 PAR2在直肠黏膜中高度表达，肠道PAR2活化后大鼠内脏敏感性明显增加。
ABSTRACT: Objective To investigate the role of PAR2 in the visceral sensitivity of IBS patients by observing the expression of rectal PAR2 in patients with irritable bowel syndrome and the effect of exogenous PAR2 on visceral sensitivity. Methods Based on Rome III criteria, 16 patients with constipation predominant IBS (IBS-C), 18 patients with diarrhea predominant IBS (IBS-D), and 18 controls were selected from our hospital inpatient and outpatient departments. All the patients received colonoscopic examination and rectal mucosa biopsies. The expression of rectal mucosa PAR2 was observed by immunohistochemistry and Real-time fluorescence quantitative PCR. We studied the abdominal reactions by administering the PAR2 agonist in the rectal mucosa of rats to explore whether PAR2 is involved in visceral sensitivity. Results The results of PAR2 immunohistochemistry showed that PAR2 was mainly expressed in intestinal epithelial cells, especially in the villi; in addition, endothelial cells were also found positive. While the integral optical density (IA) of PAR2 expression did not significantly differ between IBS-D or IBS-C patients and controls according to the IPP image analysis. The PAR2 mRNA level in IBS-D or IBS-C patients was not significantly different from that of the control group by Real-time PCR analysis. There was no significant difference between the IBS-D and IBS-C groups. The EMG activity significantly increased in a volume-dependent manner during the rectal balloon expansion in the PAR2 agonist group. However, there was little EMG activity when the balloon was not dilated. The area under the curve in the PAR2 agonist group with 0mL, 0.4mL and 0.6mL of distension volume did not differ compared with that of the vehicle group. When the balloon volume increased to 0.8mL, 1.0mL and 1.2mL, the EMG activity was statistically significant (P<0.01) in the PAR？？2 agonist group compared with the control group. Conclusion PAR2 is highly expressed in the rectal mucosa of IBS patients. Administration of