CAJ | 학술논문

目的：观察齐墩果酸(OA)联合他克莫司(FK506)对肾移植大鼠1型和2型辅助T(Th1/Th2)细胞的影响，探讨将OA应用于肾移植领域的价值。方法：以BN大鼠为供体，LEW大鼠为受体，建立大鼠同种异体肾移植模型。将48只受体大鼠按照随机数字表法均分为对照组、OA组、FK506组、OA+FK506组，术前1 d开始进行药物干预。记录每组6只大鼠存活时间，并监测其血清肌酐浓度。每组的另外6只大鼠则在术后第5天，用多功能流式点阵仪(Luminex)检测Th1细胞分泌的干扰素-γ(IFN-γ)、白介素-2(IL-2)以及Th2细胞分泌的白介素-4(IL-4)、白介素-6(IL-6)的血清浓度；酶联免疫斑点法(ELISpot)检测表达IFN-γ、IL-2、IL-4、IL-6的T细胞频率。结果：与其他各组比较，OA+FK506组的移植肾存活时间显著延长。与对照组比较，FK506组和OA+FK506组的血清IL-2的浓度显著降低，而OA+FK506组的降低更明显；各药物处理组血清IFN-γ、IL-4、IL-6的浓度显著降低，而OA+FK506组的降低更明显；表达IFN-γ、IL-2、IL-4、IL-6的T细胞频率明显下降，而OA+FK506组的下降更明显。结论：OA能协同FK506抑制Th1/Th2细胞，减轻排斥反应，最终促进大鼠移植肾存活。在临床肾移植领域，OA具有协同FK506促进移植肾存活的潜力。
목적：관찰제돈과산(OA)연합타극막사(FK506)대신이식대서1형화2형보조T(Th1/Th2)세포적영향，탐토장OA응용우신이식영역적개치。방법：이BN대서위공체，LEW대서위수체，건립대서동충이체신이식모형。장48지수체대서안조수궤수자표법균분위대조조、OA조、FK506조、OA+FK506조，술전1 d개시진행약물간예。기록매조6지대서존활시간，병감측기혈청기항농도。매조적령외6지대서칙재술후제5천，용다공능류식점진의(Luminex)검측Th1세포분비적간우소-γ(IFN-γ)、백개소-2(IL-2)이급Th2세포분비적백개소-4(IL-4)、백개소-6(IL-6)적혈청농도；매련면역반점법(ELISpot)검측표체IFN-γ、IL-2、IL-4、IL-6적T세포빈솔。결과：여기타각조비교，OA+FK506조적이식신존활시간현저연장。여대조조비교，FK506조화OA+FK506조적혈청IL-2적농도현저강저，이OA+FK506조적강저경명현；각약물처리조혈청IFN-γ、IL-4、IL-6적농도현저강저，이OA+FK506조적강저경명현；표체IFN-γ、IL-2、IL-4、IL-6적T세포빈솔명현하강，이OA+FK506조적하강경명현。결론：OA능협동FK506억제Th1/Th2세포，감경배척반응，최종촉진대서이식신존활。재림상신이식영역，OA구유협동FK506촉진이식신존활적잠력。
Objective:To investigate the effect of Oleanolic Acid(OA) combined with Tacrolimus(FK506) on T helper cells(Th1/Th2) in rats after renal transplantation,and assess the possibility that OA synergizes FK506 based immunosuppressant,thus acting as an clinical immunosuppressive combination to promote renal allograft survival and function.Method:Renal allogenic grafting was performed on BN rats as donors and LEW rats as recipients. Forty male LEW rats were randomly divided into four groups:control group(n=12),OA group(n=12),FK506 group(n=12),OA+FK506 group(n=12),and then interventions were made from 1 day before renal transplantation (RTx). Concentrations of serum creatinine in rats(n=6) were regularly examined and survival length of rats(n=6) were recorded in each group after RTx. In each group(n=6),concentrations of proinflammatory cytokines(IFN-γ,IL-2,IL-4,IL-6) were analyzed by Luminex, and also T-cell phenotypes(IFN-γ,IL-2,IL-4,IL-6) were analyzed by ELISpot on 5 days after RTx.Result:Renal allograft survival in OA+FK506 group was markedly prolonged as compared to other groups. A significant decrease in IL-2 was demonstrated in OA group and OA+FK506 group as compared to control group, meanwhile more significant decrease in that was demonstrated in OA+FK506 group. A significant decrease in IFN-γ,IL-4 and IL-6 in administration groups was demonstrated as compared to control group,meanwhile more significant increase in that was demonstrated in OA+FK506 group. A significant decrease in frequencies of T cells secreting IFN-γ,IL-2,IL-4 and IL-6 in administration groups was demonstrated as compared to control group,meanwhile more significant decrease in those was demonstrated in OA+FK506 group. A significant decrease in frequencies of T cells secreting IFN-γ,IL-2,IL-4 and IL-6 in administration groups was demonstrated as compared to control group,meanwhile more significant decrease in those was demonstrated in OA+FK506 group.Conclusion:OA and FK506 exert synergistic effect towards markedly inhibiting Th1/Th2 cells,decreasing rejection,and further enhancing renal allograft survival and function in rats. We hypothesized that novel therapeutic approaches involving combination of OA combined with FK506 will produce potential beneficial outcomes in clinical renal transplantation.