The Renal Protection And Mechanisms Of Hirudo In Unilateral Ureteral Obstruction Rats With Tubulointerstitial Fibrosis

Objective To investigate the effect of hirudo on expression ofKidney injury molecule-1(KIM-1)、 intercellular adhesion molecule-1(ICAM-1) and inflammatory cell infiltration in renal tubulointerstitiallesio-ns in rat with unilateral ureteral obstruction， and explore mechanism ofhirudo delay the progress of renal interstitial fibrosis.Methods The rat with tubulointerstitial fibrosis induced by unilateralureteral obstruction (UUO) was researched.120male Spraguo Dawley rats wererandomly divided into six equal groups of twenty. Sham-operated group(SOR), in which rats were perfused stomach with saline; Unilateral ureteralobstruction group (UUO), in which rats were also perfused stomach withsaline; Heparin sodium group, in which rats were injected intraperitoneallywith heparin sodium; High dose hirudo group, middle dose hirudo group,and low dose hirudo group, in these groups, rats were perfused stomach withcorresponding doses of hirudo. Ten rats of each group were killedrespectively at7th、14th day after surgery. Left renal tissue were embeded inparaffin. Histological change were observed by PAS and Massion staining.The renal tissue protein expression and localization of KIM-1、 ICAM-1、CD68、 TGF-β1was examined by immunological histochemistry. SPSS17.0package was used for statistical analysis.Results①PAS and Masson staining show SOR group is notunusual, there were no obvious pathological changes in renal tubulointerstitium on two time points. Renal interstitial and tubular expansion,vacuoles degeneration and atrophy, necrosis, widened renal interstitialedema, inflammatory cell infiltration, and renal interstitial fibrosis can beseen on day7in UUO group. The above-mentioned renal lesions wereenhenced on day14. Renal tubulointerstitium injury scores weresignificantly higher on day7and day14in UUO group, compared with SORgroup (p <0.05). The renal injury scores in the all treatment groups wasremarkably decreased, compared with UUO group（p<0.05）. And the scorein high dose hirudo group was obviously lower than other treatment groups.but there is no statistical difference in renal injury scores between Heparinsodium group and Middle dose hirudo group on day7and day14.②Immunohistochemical staining showed that the renal tissue proteinexpression of KIM-1、 ICAM-1、 CD68、 TGF-β1were no or lower in SORgroup on the two time points. The these expressions were significantlyupregulated in UUO group on day7and day14(p <0.05). After treatmentwith hirudo and Heparin sodium, their expression were decreased comparewith UUO group (p <0.05). High dose group was more visible in reducingtheir expression in renal tissue than other groups (p <0.05).③The levels of KIM-1expression in renal tubulointerstitium was positivelycorrelated with kidney damage index (P<0.05), except low dose hirudo group onday7and day14, and was also positively correlated with TGF-β1expression(P<0.05)，except low dose hirudo group on day7and day14and middle dosehirudo groupon day7.Conclusion①The levels of KIM-1expression in renal tubulointerstitium inUUO model rats was closely related with renal tubulointerstitium injury score and thelevels of TGF-β1expression.②Hirudo can delay the progress and development of renaltubulointerstitial ffibrosis in unilateral ureteral obstruction rats， suggestingthat hirudo may be through down-regulating the expression of KIM-1、ICAM-1and accumulation of inflammatory cells， reducing inflammationreaction, thereby inhibiting fibrosis factors associated expression of TGF–β1, and there is a certain dose-dependent relationship．...