Department of Gastroenterology, The Second Affiliated Hospital of School of Medicine, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
Department of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an 710068, Shaanxi Province, China.
World J Gastroenterol. 2017 Sep 14;23(34):6339-6349. doi: 10.3748/wjg.v23.i34.6339.
To evaluate the role of P2Y1R in visceral hypersensitivity in rats with experimental irritable bowel syndrome.
A rat model of irritable bowel syndrome was generated by intra-colonic administration of acetic acid (AA) and assessed by histology and myeloperoxidase (MPO) activity assay. Then P2Y1R expression in the colonic tissue was detected by Western blot. In order to explore the regulatory role of P2Y1R in visceral hypersensitivity, an agonist (MRS2365) and an antagonist (MRS2179) of P2Y1R were intra-colonically administered and effects were tested through a colorectal distension test. The abdominal withdrawal reflex and abdominal electromyography were tested during the course.
Model assessment tests showed an obvious inflammatory reaction that appeared on the 2 d after the AA injection, and the inflammatory reaction gradually recovered and almost disappeared on the 7 d. The model finished on day 8 and showed a clear feature of IBS that had no organic lesion. The average expression of P2Y1R was significantly higher in the AA group than in the naïve group (0.319 ± 0.02 0.094 ± 0.016, < 0.001). MRS2365 could effectively raise the colonic hypersensitivity status at intervention doses of 10 (AUC value from 0.30 ± 0.089 to 1.973 ± 0.127 mv·s, < 0.01) and 100 μmol/L (AUC value from 0.290 ± 0.079 to 1.983 ± 0.195 mv·s, < 0.01); MRS2179 could effectively reduce the hypersensitivity status at intervention dose of 100 μmol/L (from a mean baseline AUC value of 1.587 ± 0.099 mv·s to 0.140 ± 0.089 mv·s, < 0.0001). Differences between the MRS2179 group (1.88 ± 1.45) and either the MRS2365 group (3.96 ± 0.19) or the combined treatment (MRS2179 and MRS2365) group (3.28 ± 0.11) were significant ( < 0.01).
P2Y1R plays a regulatory role in visceral hypersensitivity in rats with experimental IBS. Specific antagonists of P2Y1R may have potential therapeutic value in treating abdominal pain in IBS.
评估 P2Y1R 在实验性肠易激综合征大鼠内脏敏感性中的作用。
通过向大鼠结肠内给予乙酸（AA）建立肠易激综合征模型，并通过组织学和髓过氧化物酶（MPO）活性测定进行评估。然后通过 Western blot 检测结肠组织中 P2Y1R 的表达。为了探讨 P2Y1R 在内脏敏感性中的调节作用，给予 P2Y1R 的激动剂（MRS2365）和拮抗剂（MRS2179），并通过结肠扩张试验进行测试。在此过程中测试腹壁退缩反射和腹壁肌电图。
模型评估测试显示，AA 注射后第 2 天出现明显的炎症反应，炎症反应逐渐恢复，第 7 天几乎消失。模型于第 8 天完成，表现出 IBS 的明显特征，无器质性病变。AA 组 P2Y1R 的平均表达明显高于空白组（0.319 ± 0.02 vs. 0.094 ± 0.016，<0.001）。干预剂量为 10 （AUC 值从 0.30 ± 0.089 增加到 1.973 ± 0.127 mv·s，<0.01）和 100 μmol/L （AUC 值从 0.290 ± 0.079 增加到 1.983 ± 0.195 mv·s，<0.01）时，MRS2365 能有效提高结肠高敏状态；干预剂量为 100 μmol/L 时，MRS2179 能有效降低高敏状态（从平均基线 AUC 值 1.587 ± 0.099 mv·s 降低至 0.140 ± 0.089 mv·s，<0.0001）。MRS2179 组（1.88 ± 1.45）与 MRS2365 组（3.96 ± 0.19）或联合治疗（MRS2179 和 MRS2365）组（3.28 ± 0.11）之间的差异均有统计学意义（<0.01）。
P2Y1R 在实验性 IBS 大鼠内脏敏感性中起调节作用。P2Y1R 的特异性拮抗剂可能在治疗 IBS 腹痛方面具有潜在的治疗价值。
