肠激安胶囊对腹泻性肠易激综合征模型大鼠腹痛的影响及分子机制研究Δ

摘要

OBJECTIVE:To investigate the effect of Changji’an capsules on abdominal pain and the molecular mechanism re-lated to calcitoningene-related peptide(CGRP)and corticosterone(CORT)in diarrhea-predominant irratable bowel syndrome(IBS-D)model rats. METHODS:After the rat models of IBS-D were established by the method of separation of breast mick combined with stimulation with acetic acid,the rats were randomly divided into model group(isometric normal saline),pinaverium bromide group(0.018 g/kg),and Changji’an capsules high,medium and low dose groups(2.812 g/kg,1.406 g/kg and 0.703 g/kg),and another SD rats were included in the normal control group(isometric normal saline). The drugs were given to the rats once a day for consecutive 14 d,ig. Injection of normal saline method was adopted to determine the rat’s sensibility to abdominal pain. The en-zyme-linked immunosorbent assay(ELISA)was adopted to determine the content of CORT in the serum of the rats. Subjected to re-verse transcription polymerse chain reaction(RT-PCR)was adopted to determine the expression of CGRP mRNA in the hypothala-mus and colon tissues of the rats. RESULTS:Compared with normal control group,threshold values of arching the back and stick-ing out the abdomen were decreased,the content of CORT in serum and expression of CGRP mRNA in the hypothalamus and co-lon tissues in model group were increased,with significant difference(P<0.01). Compared with model group,threshold values of arching the back and sticking out the abdomen were increased,the content of CORT in serum and expression of CGRP mRNA in the hypothalamus and colon tissues in pinaverium bromide group and Changji’an capsules high and medium dose groups were de-creased;the threshold value of arching the back in Changji’an capsules low dose group were increased,with significant difference (P<0.01 or P<0.05). CONCLUSIONS:Changji’an capsules can improve the abdominal pain in rats with IBS-D by a mechanism that may be related to the decrease in the expression of CGRP mRNA in the hypothalamus and colon tissues and the reduc-tion of the content of CORT in serum.%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 mRNA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 mRNA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 mRNA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 mRNA表达和降低血清中CORT含量有关。