Establishment Of IC Model In Rats And Analysis On The Effect Of PGE1,SF In The Model

Objective: 1.To establish a model of IC in rats and investigate the pathological mechanism of IC.2.To investigate the effect and therapeutic mechanism of Lipo-PGE1 in IC.The evidences for clinical use can be offered from the result.3.In order to find a new way to cure the IC, SF were used to treat the rats suffered IC.From the result we can estimate the effect and explore the therapeutic mechanism of SF.Methods: 1 .The IC model of rats was induced by photochemical way.We irradiated proximate colon of rats by laser after intravenous injecting PSD-007,which is a photosensitive drug.Then we killed the rats at different end points(0,1,3,5,7,14d) and measured the dynamic changes of the SOD, MDA,LI of colon mucosa and TNF-a of serum.2. IC model rats were divided into different groups and treated by different dose (0.5, 1, 2ug/kg) of Lipo-PGE1.The rats of control group were given physiologic saline.All rats were killed after 5 days' continuous treatment.Then the differences of LI, SOD, MDA, 6-keto-PGF1α, TXB2 and expression of TNF-α, ICAM-1 between control group and treating groups were measured.3. IC model rats were divided into different groups and treated by different dose(20, 40, 80mg/kg) of SF.The rats of control group were given physiologic saline.All rats were killed after 5 days' continuous treatmrnt.We measured the differences of LI, ET-1, SOD, MDA, 6-keto-PGF1α, TXB2 and expression of TNF-α, ICAM-1 between control group and treating groups.Results: 1. Rats showed symptoms such as decrease of foodintaking and activity, diarrhea,bloody stools after laser irradiation.Compared with the control group,LI and TNF-α achieved peak value(LI 3.25±0.46 and TNF-α 1.89±0.38,PO.01) on 5th day, SOD activity decreased significantly(19.12±6.70,P<0.01) on 3rd day,MDA increased significantly(30.38±4.41,P<0.01) on 3rd day.All of them turned normal on 14th day.There is a significantly positived correlation between LI with MDA and TNF-a.The correlation coefficients are 0.5213,0.5503(P<0.01)o There is a significantly negative correlation between LI with SOD.The correlation coefficient is -0.7223(P<0.01)o2.After treatment by different dose of Lipo-PGEl,the results revealed that LI had a significiant decrease in medium dose group and large dose group compared with control group.The more dose of Lipo-PGEl was used,the less phenomenons such as inflammatory cells infiltrating in mucosa and submucosa, glandular cell degeneration and necrosis, thromb in vessel were found in pathohistology observation.MDA,TXB2,6-keto-PGFla/TXB2,positive expression of TNF-ou ICAM-1 decreased signicantly in medium dose group and large dose group compared with control group.SOD activity is signicantly increased in medium dose group and large dose group compared with control group.3.After the treatment by different dose of SF,the results revealed that LI had a significiant decrease in medium dose group and large dose group compared with control group. Pathohistology observations displayed that the phenomenons such as inflammatory cells infiltrating, glandular cell degeneration and necrosis, thromb in vessel extenuated.The indicatrixs of ET-1,MDA, TXB2,6-keto-PGFla/TXB2, positive expression of TNF-cu ICAM-1 decreased signicantly and SOD activity increased signicantly in medium dose group and large dose group compared with control group.Conclusion: l.The IC model induced by photochemical way has many advantages,such as easy operability, good repeatability,fine reality and low death rate,which is a fundament for future study. SOD> MDA and TNF-a play important roles in the pathological mechanism of IC.The changes of colon mucosal SOD and MDA can be taken as early indicatrixes in the development of IC.2. Lipo-PGEl has a good effect to cure IC. There is a significant decrease ofLI after therapy and the effect depend on the Lipo-PGEl's dose.Little dose leads to little effect,more dose leads to more effect in safety range. Therapeutic mechanism of Lipo-PGEl in IC is about anti-thrombogenesis, improving tissue microcirculation, lessening Inflammatory reaction and oxygen free radical generation.3. SF is a effective medicine to cure IC, which can decrease the model rats' Ll.It can hardly bring about effect if the dose is too little.Its antagonism effect to ET-1 is the main therapeutic mechanism of IC.The study offers a new way to cure IC.