Establishment Of IC Model In Rats And Analysis On The Effect Of Urokinase In The Model

Objective : 1.To establish a model of IC in rats and investigate the pathological mechanism of IC.2. IC model rats were divided into different groups after treated by Urokinase, then measured the dynamic changes of the SOD, MDA and MPO, and expression of p-selectin, to investigate the effect p-selectin and therapeutic mechanism of Urokinase in IC. The evidences for clinical use can be offered from the result.Methods: 1. The rats of IC model were induced by photochemical way. We irradiated proximate colon of rats for 10 minutes by laser after intravenous injecting PSD-007, which is a photosensitive drug. All rats were killed after 1 hour. Measured the dynamic changes of the LI, and observed the injury of colon mucosa and formation of thrombus.2.IC model rats were divided into different groups after treated by Urokinase. The rats of control group were given physiologic saline. Then we killed the rats at different end points (0.5,1,3,6,18, 24 hour) and measured the dynamic changes of the SOD, MDA, MPO of the colon mucosa and serum, and LI and expression of p-selectin of the colon mucosa.Results: 1 .After 1 hour of ending the laser irradiation, colon mucosa showed hyperemia and edema .There were not erosion or ulcer. We can see lots of PMNs and lymphocytes and find hemorrhage under light microscope. Compared with the control group, LI achieved peak value at 1 hour, P<0.05. There were thrombi formatted in the little blood vessels in 9 specimens of 10. But in the control groups, we only see a little of PMNs and lymphocytes, can not find hyperemia, edema, hemorrhage and thrombus.2. After treatment by Urokinase, LI got bad gradually, at 24 hours there were ulcer in 6 rats, compared with MX group, p<0.01. In the tissues, SOD activity of experiment groups increased after I/R, it reached the peak at 0.5 hour after reperfusion and then it decreased gradually. At 3 hours it reached the minimum. Then they showed another fluctuated at 6 hours and 18 hours. At 24 hours the SOD increased gradually. In the serum, compared with KF group, MX group's SOD decreased significantly, p<0.01. In the experiment groups, SOD increased gradually. At 24 hours, it changed insignificantly. In the tissues, compared with KF group, MDA content increased, but p>0.05 in MX group. After I/R, it reached peak at 0.5 hour, but it decreased at 1hour. In the after hours, it changed like before. At 24 hours, it decreased again, and compared with KF group p>0.05. In the serum, the MDA content of MX group increased after ischemia, compared with KF group, it reached the minimum at 3 hours after reperfusion, compared with MX group p<0.05. Then it increased little by little, only to 24 hours, compared with MX group p<0.05. About MPO content, in the tissues it increased gradually after ischemia. It reached the peak at 24 hours after I/R, and from 1 hour, the MPO content compared with MX group, p<0.05. In the serum, it reached the peak after ischemia 1hour (compared with KF group, p<0.01), then the MPO content decreased gradually, and it reached the minimum at 24 hours. After I/R, expression of P-selectin increased gradually, it reached the peak at I/R1,then decreased gradually and got to the minimum at I/R24. There is a significantly positived correlation between LI with tissue MDA and MPO, and between P-selectin and serum MPO. The correlation coefficients are 0.3229, 0.6197, 0.5539 (p<0.05, p < 0.01, p < 0.01).Between P-selectin and serum SOD are negative correlation-0.6493,p<0.01).Conclusion: 1.The IC model induced by photochemical way has many advantages, such as easy operability, good repeatability, fine reality and low death rate, which are a fundament for future study.2. OFR plays important roles in the pathological mechanism of IC. P-selectin can mediate leukocytic margination, adhesion and transmigration, then resulted in the inflammation. The changes of colon mucosal MDA, MPO and P-selectin can be taken as early indicatives in the development of IC.