鞘内注射促肾上腺皮质激素释放因子对肠易激综合征模型大鼠内脏高敏感性的影响

Inhibition of visceral hypersensitivity in irritable bowel syndrome model rat by intrathecal administration of corticotrophin releasing factor

目的研究鞘内注射促肾上腺皮质激素释放因子（CRF）对肠易激综合征模型大鼠内脏高敏感性的影响。方法将30只大鼠随机分成3组，每组各10只，应用化学刺激方法建立肠易激综合征大鼠模型后，分别给予鞘内注射CRF或预先腹腔注射CRF-1受体拮抗剂CP-154526后再鞘内注射CRF，对照组则注射生理盐水；实验后所有大鼠给予直肠内球囊扩张，检测球囊扩张引起腹部收缩反射的最小容量阈值及球囊不同容量扩张时腹部收缩反射的次数，以评价鞘内注射CRF对肠道敏感性的影响。应用免疫组织化学染色及计算机图像分析系统半定量分析脊髓后角即刻早基因（c-fos）表达。结果直肠内球囊扩张时，鞘内注射CRF组引起腹部收缩的最小容量阈值为（0．62±0．10）ml，高于其他2组[分别为（0．52±0．09）ml、（0．56±0．08）ml；F=3．25；P〈0．05]。直肠球囊扩张体积1．0ml时鞘内注射CRF组腹部收缩反射次数为（9．10±1．97）次，明显低于其他2组[分别为（14．4±1．71）次、（15．6±2．32）次；F=29．4；P〈0．01]；体积1．5ml、2．0ml高容量扩张时3组间差异无显著性（P〉0．05）。鞘内注射CRF组腰骶段脊髓后角c-fos阳性神经元细胞相对切面面积及OD值均明显低于其他2组（P〈0．01）。结论鞘内注射CRF能够降低肠易激综合征模型大鼠内脏高敏感性，并减少其腰骶段脊髓后角c-fos的表达。

Objective To investigate whether intrathecal administration of corticotrophin releasing factor （CRF） has an efficacy on visceral hypersensitivity in irritable bowel syndrome model rat. Methods Thirty rats were randomly divided into three groups（ n = 10 ）. After establishment of irritable bowel syndrome rat model were intrathecal injected with CRF or preemptive peritoneal injected with CP-154526 ,which is inhibitor of CRF-1 receptor, and the control group to give saline. After experiment all rat with the method of rectal balloon distention, the perception thresholds and the number of abdominal withdrawal reflexes （AWR） of different balloon volume were observed. Results The perception threshold of intrathecal administration of CRF group was （0.62 ±0.10） ml and higher than other two groups [ （0.52 ± 0. 09） ml, （ 0.56 ± 0.08 ） ml ; F = 3.25, P 〈 0.05 ]. At the same time, the number of AWR to the lower balloon content （ 1.0 ml） was （9.10 ± 1.97） in intrathecal administration of CRF group slightly lower than other two groups [ （ 14.4 ± 1.71 ）, （ 15.6 ± 2.32 ） ; F = 29.4, P 〈 0.01 ], but no difference was found to the higher balloon content （ 1.5 ml and 2.0 ml）. Besides,the areas and OD value of c-fos positive neurons in cornu posterius medullae spinalis in group with intrathecal administration of CRF were significantly lower than other two groups （ P〈 0.05）. Conclusion Intrathecal administration of CRF can degrade the visceral hyperensitivity in irritable bowel syndrome model rat,and lower expression of c-fos in CNS is probably involved in the process.