摘要
AIM: To evaluate the immunologic role and expressionsignificances of nitric oxide(NO), nitric oxide synthase(NOS),and its isoenzyme in acute rejection to liverxenografts from golden hamster in rat.METHODS: Liver transplantations were randomlydivided into five groups(n＝6-9):isografts (group I );xenografts (groupⅡ); xenografts plus cyclosporinetreatment (group Ⅲ), xenografts pluscyclophosphamide treatment combined withsplenectomy (group Ⅳ), and xenografts usingcyclophosphamide in combination with splenectomy(group Ⅳ) and xenografts using splenectomy inaddition to cyclophosphamide and cyclosporinetreatments(group V) .The levels of ALT, TNF- α, andnitric oxide production(NOx) in serum of reciprentswere examined,and expressions of type Ⅱ (iNOS) andtypeⅢ (cNOS) nitric oxide synthase(NOS)-inducibleNOS(iNOS) and constitutive NOS(cNOS) wereobserved by NADPH diaphorase histochemical andimmunohistochemical staining.RESULTS: The level of serum ALT, activity of serumTNF-α and systemic levels of NO metabolite in groupsⅡand Ⅳ were higher than those of groups Ⅰ andy(serum ALT, 2416±475, 2540±82.5) nkat. L-1 vs(556.8±43.5, 677.30±38.2 ) nkat. L-1, P＜0.01;(serum TNF-α, 353.5±16.1,444.6±28.1) ng.L-1 vs38.5±5.2, 52.0±5.7) ng.L-1, P＜0.01; (serum NOx514.6 ± 18.1, 336.0 ± 43.0 )nmol.g-1, vs 26.1 ± 5.7, 27.7±6.0) nmol.g-1, P＜0.01.Cyclosporine in group Ⅲcan repress the cellular immune response and thesynthesis of nitric oxide and the expression of NOsynthase,but not prolong the liver xenograftsurvival.The over-expression of NOS, iNOS and cNOSin liver xenograft rejection in groups Ⅱand Ⅳ weredetected by NADPH diaphorase histochemical andimmunohistochemical staining.CONCLUSION: The degrees of acute rejection can beeffectively repressed in golden hamster to rat liverxenografts with splenectomy and cyclosporine. Nitricoxide metabolites, and nitric oxide synthase and itsisoenzymes,above all inducible NOS (iNOS) can beused as potential diagnostic markers for acuterejection in liver transplantation. The cellularlocalization of nitric oxide varies according to theimmunologic status of liver xenografts, thus thinkingthat hepatocyte derived nitric oxide may be protectivein the hyporesponsive state, but hepatic injury is likelytriggered by centrilobular iNOS expression in thesuperresponsive state.
AIM:To evaluate the immunologic role and expression significances of nitric oxide(NO),nitric oxide synthase (NOS),and its isoenzyme in acute rejection to liver xenografts from golden hamster in rat. METHODS:Liver transplantations were randomly divided into five groups(n-6-g):isografts(group Ⅰ); xenografts(group Ⅱ);xenografts plus cyclosporine treatment(group Ⅲ),xenografts plus cyclophosphamide treatment combined with splenectomy(group Ⅳ),and xenografts using cyclophosphamide in combination with splenectomy (group Ⅳ)and xenografts using splenectomy in addition to cyclophosphamide and cyclosporine treatments(group Ⅴ).The levels of ALT,TNF-α,and nitric oxide production(NOx)in serum of reciprents were examined,and expressions of type Ⅱ(iNOS)and typeⅢ(cNOS)nitric oxide synthase(NOS)-inducible NOS(iNOS)and constitutive NOS(cNOS)were observed by NADPH diaphorase histochemical and immunohistochemical staining. RESULTS:The level of serum ALT,activity of serum TNF-α and systemic levels of NO metabolite in groups IIand IV were higher than those of groups Ⅰ andⅤ (serum ALT,2416±475,2540±82.5)nkat.L^(-1)vs (556.8±43.5,677.30±38.2)nkat.L^(-1),P<0.01; (serum TNF-α,353.5±16.1,444.6±28.1)ng.L^(-1),vs 38.5±5.2,52.0±5.7)ng.L^(-1),P<0.01;(serum NOx 514.6±18.1,336.0±43.0)nmol.g^(-1),vs 26.1±5.7,27. 7±6.0)nmol.g^(-1),P<0.01.Cyclosporine in group Ⅲ can repress the cellular immune response and the synthesis of nitric oxide and the expression of NO synthase,but not prolong the liver xenograft survival.The over-expression of NOS,iNOS and cNOS in liver xenograft rejection in groups Ⅱand Ⅳ were detected by NADPH diaphorase histochemical and immunohistochemical staining. CONCLUSION:The degrees of acute rejection can be effectively repressed in golden hamster to rat liver xenografts with splenectomy and cyclosporine.Nitric oxide metabolites,and nitric oxide synthase and its isoenzymes,above all inducible NOS(iNOS)can be used as potential diagnostic markers for acute rejection in liver transplantation.The cellular localization of nitric oxide varies according to the immunologic status of liver xenografts,thus thinking that hepatocyte derived nitric oxide may be protective in the hyporesponsive state,but hepatic injury is likely triggered by centrilobular iNOS expression in the superresponsive state.
