An Experimental Study Of Ureteral Strictures By Endoscopic Procedures And The Intervention Of The Strictures In Rabbits

Objective: To establish a reliable model of the ureteral injury and to observe pathologicalchanges and to text the sensitive markers of the fibrotic process after the ureteral injury inrabbits. Investigate the fluctuation characteristic of the different sensitive makers duringthe tissue scaring and evaluate the anti-fibrotic role of enalapril in rabbits.Methods:40New Zealand rabbits were randomly divided into mechanical damage groupand thermal damage group, mechanical damage group were divided into subgroup a andsubgroup b, thermal damage group were divided into sub group c and sub group d. TheEGF、TGF-β、CTGF、KGF、COLIa1、COLIa2、COLⅢ、FN of the impaired ureter andthe contralateral normal ureter were quantified by RT-PCR technique to find out thesensitive biomarkers of the ureteral fibrosis.The fluctuation of the markers during2to4weeks were also noted,pathological changes were also observed. In group B,40NewZealand rabbits were also randomly divided into mechanical damage group and thermaldamage group, mechanical damage group were divided into sub group one and sub grouptwo, thermal damage group were divided into subgroup three and subgroup four. Theenalapril10mg/Kg/d was given in experimental group,use group A in the same period asthe control group.The specimens of ureter were harvest2weeks and4weeks after theintervention and the RT-PCR and pathologicalsection were carried out.Results: The ureteral injury models were established successfully.In group A，HE stainingresults show the injured ureter proliferate significantly in the submucosa and themuschlar,fibroblast proliferate obviously,while the ureteral mucosa is almost nomal,groupc have higher fibrosis than group a, group b have higher fibrosis than group a, group dhave higher fibrosis than group c, there is no significant difference between group b andgroup d.By RT-PCR screening, EGF、TGF-β、CTGF、COLIa1、COLIa2、COLⅢ、FNwere found to be significantly elevated than the other markers(all P <0.05).Group c has a higher expression than group a(all P <0.05), group b has a higher expression than groupa,group d has a higher expression than group c(all P <0.05), there is no significantdifference between group b and group d（all P>0.05）.The expression of KGF in each grouphas no significant increase（all P>0.05）. For the enalapril experimentation,the expressionsof EGF、TGF-β、CTGF、FN in enalapril group were significantly lower in Group B thanthose in the group A(all P <0.05), group one has a lower expression than group a, grouptwo has a lower expression than group b, group three has a lower expression than group c,group four has a lower expression than group d (all P <0.05).However,there were nostatistic significance for COLIa1、 COLIa2、 COLⅢ between the two groups （allP>0.05）.Besides, HE staining shows there is no significant improvement than the groupA.Conclusions: The essence of ureteral injury is scar formation of the ureter middle wall.EGF、TGF-β、CTGF、COLIa1、COLIa2、COLⅢ、FN were found to be significantlyelevated in the ureteral fibrosis and scarring after the ureteral lesion. Thermal damage canmore likely to cause ureteral fibrosis than mechanical damage, the longer the injury time,the higher the degree of fibrosis. Enalapril can reduce the expression of EGF、TGF-β、CTGF、FN significantly and inhibit the expression of COLIa1、COLIa2、COLⅢ,but can’tinhibit ureter fibroblast proliferation, suggesting that pharmacological interventions can’twell reduce the incidence of ureteral stricture, avoiding cavity ureteral injury is the primarymeans of prevention of ureteral strictures and the only way to reduce the incidence ofureteral strictures.