“补骨脂-肉豆蔻”对IBS内脏高敏感大鼠CRF及其受体的调控

The effect of extracts from Psoralea corylifolia L and Nutmeg on the corticotropin releasing factor and its receptor expression in model of IBS visceral hypersensitivity rats

目的:观察"补骨脂-肉豆蔻"醇提物对母子分离结合乙酸灌肠诱导IBS内脏高敏感大鼠促肾上腺皮质激素释放因子(CRF)及其受体的影响。方法:将新生SD大鼠随机分6组,每组8只,除正常组外,其余各组大鼠采用母子分离结合乙酸灌肠法复制IBS内脏高敏感大鼠模型,于造模后第6周起,分别给予"补骨脂-肉豆蔻"醇提物(15g/kg、10g/kg、5g/kg),匹维溴铵(50mg/kg)灌胃,1次/d,连续2w。治疗后评价其腹部收缩反射(AWR)阈值,采用酶联免疫吸附法(ELISA)检测大鼠血浆中P物质(SP)和降钙素基因相关肽(CGRP)的含量;RT-qP CR和Western Blot检测大鼠结肠组织促肾上腺皮质激素释放因子(CRF),CRF1型受体(CRFR1)和CRF2型受体(CRFR2)的含量。结果:"补骨脂-肉豆蔻"醇提物(15g/kg、10g/kg)不仅能升高内脏高敏感性大鼠腹部回缩反射(AWR)阈值,还能降低血浆中SP、CGRP的含量,同时,"补骨脂-肉豆蔻"醇提物(15g/kg、10g/kg、5g/kg)能不同程度地降低结肠CRF、CRFR1表达及CRFR1/CRFR2的比值。结论 :"补骨脂-肉豆蔻"对内脏高敏感性大鼠有一定的治疗作用,其作用机制可能与调控CRF及其受体,从而提高内脏痛阈,改善肠道过敏状态有关。

Objective： To study the effect of alcohol extracts from Psoralea corylifolia L ﹠ Nutmeg on the corticotropin-releasing factor（ CRF） and its receptor expression in model of visceral hypersensitivity rats. Methods： Newborn SD rats were randomly divided into six groups,eight rats in each group. Except for nomal group,the rest groups were given separation and acetic acid-induced visceral hypersensitivity rats. The treatment groups were oral given alcohol extracts from Psoralea corylifolia L ﹠ Nutmeg（ 15 g / kg,10 g / kg,5g / kg）,and pinaverium bromide（ 50 mg /kg） once a day for two weeks. Then the threshold of abdominal withdrawal reflex was measured at 6th week with rectal distension. The levels of P substance（ SP）,calcitonin gene-related peptide（ CGRP） in rat plasma were determined by enzyme-linked immuno sorbent assay（ ELISA）. Moreover,real-time fluorescent quantitative PCR was performed to detect the expressions of CRF,CFRR1,and CFRR2 mRNA,and Western blotting to determine the expressions of CRF,CFRR1,and CFRR2 protein. Results： Compared with model group,the alcohol extracts from Psoralea corylifolia L ﹠ Nutmeg（ 15 g / kg,10 g / kg） not only significantly increased the pressure threshold of abdomen lifting and body arching,but also effectively decreased the levels of SP,CGRP in rat plasma,inhibited expressions of CRF,CRFR1 in the colon,and declined the ratio of CRFR1 / CRFR2. Conclusion： The alcohol extracts from Psoralea corylifolia L ﹠ Nutmeg has certain treatment function on model of visceral hypersensitivity rats,which might be related to the affect that expressions of CRF and its receptor,modulate visceral hypersensitivity by increasing pain threshold.