Analgesic effects of JCM-16021 on neonatal maternal separation-induced visceral pain in rats
Analgesic effects of JCM-16021 on neonatal maternal separation-induced visceral pain in rats
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DOI：
10.3748/wjg.v16.i7.837
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发表时间：
2010-02-21
影响因子：
4.3
通讯作者：
Sung, Joseph J. Y.
中科院分区：
文献类型：
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作者：
Bian, Zhao-Xiang;Zhang, Man;Sung, Joseph J. Y.
目的：探讨中药复方JCM-16021的药理作用及其作用机制。方法：JCM-16021由7种中药植物原料组成。配方中所有原料均按中国药典（2005年版）所列质量控制标准进行检验。在新生儿母体分离 (NMS) 模型中，雄性 Sprague-Dawley 大鼠从出生后第 2 天到第 14 天每天接受母体分离，或不进行特殊处理 (NH)。从出生后第60天开始，大鼠口服JCM-16021（每天2、4、8g/kg），每天两次，持续28天。用 Power Lab 系统（AD Instruments International）记录的痛阈压力和外斜肌响应结直肠扩张的肌电活动作为疼痛指数进行测试。分析大鼠结肠中血清素（5-HT）和5-羟基吲哚乙酸（5-HIAA）浓度的变化；还用免疫组织化学方法评估了大鼠结肠中的肠嗜铬细胞数量和血清素转运蛋白。 结果：与 NH 大鼠相比，NMS 治疗显着降低了痛阈压（37.4 +/- 1.4 mmHg）（57.7 +/- 1.9 mmHg，P < 0.05）。 JCM-16021治疗后，痛阈压力较治疗前显着升高（高剂量组为34.2 +/- 0.9 mmHg vs 52.8 +/- 2.3 mmHg，中剂量组为40.2 +/- 1.6 mmHg vs 46.5 +/- 1.3 mmHg，39.3 +/- 0.7 mmHg vs 46.5 +/- 1.6 低剂量组为mmHg，P < 0.05）。 ICM-16021 还显着且剂量依赖性地降低分级结直肠扩张 (CRD) 的肌电图活性（高剂量组的平均 Delta AUC 值为：0.17 +/- 0.03、0.53 +/- 0.15、1.06 +/- 0.18、1.22 +/- 0.24；0.23 +/- 0.04， 0.68+/-0.17、1.27 中剂量组+/-0.26、1.8+/-0.3；与 NMS 媒介物组相比，低剂量组在压力 20、40、60、80 mmHg 时为 0.29 +/- 0.06、0.8 +/- 0.16、1.53 +/- 0.24、2.1 +/- 0.21。压力为 20、40、60、80 mmHg 时，平均 AAUC 值为：0.57 +/- 0.12、1.33 +/- 0.18、2.57 +/- 0.37、3.08 +/- 0.37（P < 0.05）。与 NMS 载体组（93.11 +/- 9.85）相比，ICM-16021 治疗显着降低了 5-HT 浓度（高、中、低剂量组：60.25 +/- 5.98 ng/100 mg、60.32 +/- 4.22 ng/100 mg、73.31 +/- 7.65 ng/100 mg）纳克/100 毫克，P < 0.05)；与 NMS 赋形剂组 (51.75 +/- 1.98 ng/100 mg，P < 0.05);但并没有改变大鼠结肠中肠嗜铬细胞的数量。此外，NMS 大鼠的 SERT 表达（n = 10）高于 NH 大鼠（n = 8，P < 0.05）。与NMS组相比，JCM-16021治疗显着降低SERT表达（P < 0.01-0.001）。结论：JCM-16021可以减轻内脏高敏感性，这种镇痛作用可能是通过大鼠结肠中的5-羟色胺信号通路介导的。 (C)2010年百事登。版权所有。
AIM: To investigate the pharmacological effect of JCM-16021, a Chinese herbal formula, and its underlying mechanisms.METHODS: JCM-16021 is composed of seven herbal plant materials. All raw materials of the formula were examined according to the quality control criteria listed in the Chinese Pharmacopeia (2005). In a neonatal maternal separation (NMS) model, male Sprague-Dawley rats were submitted to daily maternal separation from postnatal day 2 to day 14, or no specific handling (NH). Starting from postnatal day 60, rats were administered JCM-16021 (2, 4, 8 g/kg per day) orally twice a day for 28 d. Pain threshold pressure and electromyographic activities of external oblique muscles in response to colorectal distention recorded with a Power Lab System (AD Instruments International), were tested as pain indices. Changes in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the colon of rats were analyzed; the enterochromaffin cell numbers and serotonin transporter in the colon of rats were also evaluated with an immunohistochemistry method.RESULTS: NMS treatment significantly reduced pain threshold pressure (37.4 +/- 1.4 mmHg), as compared to that of NH rats (57.7 +/- 1.9 mmHg, P < 0.05). After JCM-16021 treatment, the pain threshold pressure significantly increased when compared to that before treatment (34.2 +/- 0.9 mmHg vs 52.8 +/- 2.3 mmHg in the high dose group, 40.2 +/- 1.6 mmHg vs 46.5 +/- 1.3 mmHg in the middle dose group, and 39.3 +/- 0.7 mmHg vs 46.5 +/- 1.6 mmHg in the low dose group, P < 0.05). Also ICM-16021 significantly and dose-dependently decreased electromyographic activity to the graded colorectal distension (CRD), (the mean Delta AUC values were: 0.17 +/- 0.03, 0.53 +/- 0.15, 1.06 +/- 0.18, 1.22 +/- 0.24 in the high dose group; 0.23 +/- 0.04, 0.68 +/- 0.17, 1.27 +/- 0.26, 1.8 +/- 0.3 in the middle dose group; and 0.29 +/- 0.06, 0.8 +/- 0.16, 1.53 +/- 0.24, 2.1 +/- 0.21 in the low dose group for the pressures 20, 40, 60, 80 mmHg), as compared to the NMS vehicle group. The mean AAUC values were: 0.57 +/- 0.12, 1.33 +/- 0.18, 2.57 +/- 0.37, 3.08 +/- 0.37 for the pressures 20, 40, 60, 80 mmHg (P < 0.05). ICM-16021 treatment significantly reduced the 5-HT concentrations (from high, middle and low dosage groups: 60.25 +/- 5.98 ng/100 mg, 60.32 +/- 4.22 ng/100 mg, 73.31 +/- 7.65 ng/100 mg), as compared to the NMS vehicle groups (93.11 +/- 9.85 ng/100 mg, P < 0.05); and increased the 5-HIAA concentrations (after treatment, from high, middle and low dosage groups: 54.24 +/- 3.27 ng/100 mg, 50.34 +/- 1.26 ng/100 mg, 51.37 +/- 2.13 ng/100 mg) when compared to that in the NMS vehicle group (51.75 +/- 1.98 ng/100 mg, P < 0.05); but did not change the enterochromaffin cell numbers in the colon of rats. In addition, NMS rats had higher SERT expression (n = 10) than NH rats (n = 8, P < 0.05). JCM-16021 treatment significantly decreased SERT expression when compared to the NMS group (P < 0.01-0.001).CONCLUSION: JCM-16021 can attenuate visceral hypersensitivity, and this analgesic effect may be mediated through the serotonin signaling pathway in the colon of rats. (C) 2010 Baishideng. All rights reserved.