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目的:研究肠激安胶囊对腹泻性肠易激综合征(IBS-D)模型大鼠腹痛的影响及降钙素基因相关肽(CGRP)与皮质酮(CORT)相关分子机制。方法:采用母乳分离联合醋酸刺激法复制IBS-D大鼠模型后,将大鼠随机分为模型(等容生理盐水)组,匹维溴铵(0.018 g/kg)组和肠激安胶囊高、中、低剂量(2.812、1.406、0.703 g/kg)组;另取SD大鼠作为正常对照(等容生理盐水)组。ig给药,每天1次,连续14 d。采用注入生理盐水法对大鼠进行腹痛敏感性测定,采用酶联免疫吸附(ELISA)法检测大鼠血清中CORT含量,采用实时荧光定量聚合酶链反应(RT-PCR)法检测大鼠下丘脑与结肠组织中CGRP m RNA的表达。结果:与正常对照组比较,模型组大鼠拱背阈值和抬腹阈值降低,血清中CORT含量增加,下丘脑与结肠组织中CGRP m RNA表达增强,差异有统计学意义(P<0.01)。与模型组比较,匹维溴铵组与肠激安胶囊高、中剂量组大鼠拱背阈值和抬腹阈值升高,血清中CORT含量减少,大鼠下丘脑及结肠组织中CGRP m RNA表达均减弱;肠激安胶囊低剂量组大鼠拱背阈值升高,差异有统计学意义(P<0.01或P<0.05)。结论:肠激安胶囊对IBS-D模型大鼠腹痛有改善作用,其作用机制可能与下调下丘脑和结肠组织中CGRP m RNA表达和降低血清中CORT含量有关。
Objective: To investigate the effect of Chang-gui-an Capsule on abdominal pain in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and the related molecular mechanisms of calcitonin gene-related peptide (CGRP) and corticosterone (CORT). Methods: The IBS-D rat model was duplicated by breast milk separation combined with acetic acid stimulation. The rats were randomly divided into model (isocitrate saline) group, piroxicam (0.018 g / kg) Medium and low dose (2.812,1.406,0.703 g / kg) group; another SD rats were used as normal control (isovolumic saline) group. ig administration, 1 day, for 14 days. The abdominal pain sensitivity of rats was measured by injecting saline, the content of CORT in serum was detected by enzyme-linked immunosorbent assay (ELISA), the content of CORT in rat hypothalamus was detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR) And CGRP m RNA expression in colon tissue. Results: Compared with the normal control group, the arch dorsal threshold and the threshold of the laparotomy in the model group decreased. The content of CORT increased in the model group. The expression of CGRP m RNA in the hypothalamus and colon tissue increased significantly. The difference was statistically significant (P <0.01). Compared with the model group, the vault back threshold and the threshold of raising the weight of the rats in the high dose and middle dose groups of Pinaverium bromide and Chang Kao An Capsule increased, and the content of CORT in the serum decreased. The expression of CGRP m RNA in the hypothalamus and the colon tissues (P <0.01 or P <0.05). The threshold of arch dorsum of rats in low dosage group of Changjian Capsule increased significantly (P <0.01 or P <0.05). CONCLUSION: Chang-gui-an capsule can improve abdominal pain in IBS-D model rats, and its mechanism may be related to the down-regulation of CGRP-mRNA expression in hypothalamus and colon and the decrease of serum CORT content.