Study On The Pharmacodynamics And Mechanism Of Visceral Hypersensitivity Of Irritable Bowel Syndrome Using The Extracts Of Psoralea Corylifolia L And Nutmeg

1 Objective(1)To compare the therapeutic effect of different extracts from Psoralea corylifolia L and Nutmeg on model of visceral hypersensitivity rats.(2)To compare the therapeutic effect of alcohol extracts from Psoralea corylifolia L and Nutmeg on model of visceral hypersensitivity rats, and its mechanism.2 Methods(1) 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.Then the threshold of abdominal withdrawal reflex was measured at 6 week with rectal distension. The treatment groups were oral given different extracts from Psoralea corylifolia L and Nutmeg and pinaverium bromide once a day for two weeks. The pathological changes and visceral hypersensitivity-related indicators were observed in IBS rats.(2) Newborn SD rats were randomly divided into six groups, including normal group, model group, alcohol extracts from Psoralea corylifolia L ﹠ Nutmeg(15g/kg,10g/kg, 5g/kg), and pinaverium bromide(50mg/kg). Except for nomal group, the rest groups were given separation and acetic acid induced visceral hypersensitivity rats. At6 th week after modeling, corresponding drugs were given to rats by intragastric administration once a day for two weeks. Then the threshold of abdominal withdrawal reflex was measured at 6th week with rectal distension. The pathological changes and visceral hypersen sitivity-related indicators were observed in IBS rats; The levels of P substance(SP), calcitonin gene-related peptide(CGRP) in rat plasma or colon were determined by enzyme-linked immuno sorbent assay(ELISA); The expression of CRF,CFRR1 were determined by immunofluorescence technique; Moreover, real-time fluorescent quantitative PCR was performed to detect the expressions of CRF, CFRR1,CFRR2, proteine kinase A(PKA), CREB, and c-fos m RNA, and Western blotting to determine the expressions of CRF, CFRR1, CFRR2, PKA, CREB, p-CREB and c-fos protein.3 Results(1)Compared with model group, different extracts from Psoralea corylifolia L and Nutmeg could increase the pressure threshold of abdomen lifting and body arching.(2)Compared with model group, extracts from Psoralea corylifolia L and Nutmeg could not only increase the pressure threshold of abdomen lifting and body arching, but also decrease the levels of SP, CGRP in the plasma or colon, inhibit expressions of CRF,CFRR1, CFRR2, PKA, CREB, p-CREB and c-fos in the colon, and the ratio of CRFR1/CRFR2 were reduced.4 Conclusion(1)Different extracts from Psoralea corylifolia L and Nutmeg has certain treatment function on model of visceral hypersensitivity rats, and the alcohol extract had better effect.(2) The alcohol extracts from Psoralea corylifolia L ﹠ Nutmeg has certain treatment function on model of visceral hypersensitivity rats, which might be related to block CRF-CREB signal transduction pathway, enhancing the visceral pain threshold,improving intestinal allergic status.