CAJ | 학술논문

目的探讨4-1BB单克隆抗体(4-1BBmAb)及激素对免疫性肝损伤的治疗作用及对CD4+CD25+T细胞的影响.方法建立刀豆蛋白A(ConA)诱导免疫性肝损伤小鼠模型,激素治疗组ConA注射2h后腹腔内注射甲泼尼龙(3 mg/kg),4-1BBmAb治疗组尾静脉注射4-1BBmAb(100 μg/只),联合治疗组同时使用甲泼尼龙(3 mg/kg)及4-1BBmAb(100 μg/只),健康对照组仅注射相同体积的0.9％氯化钠注射液.分别通过肝脏组织学、肝功能进行治疗效果的验证.分别抽取各组小鼠血液,流式细胞仪观察CD4+CD25+T细胞表达的变化.采用方差分析及t检验进行统计分析.结果健康对照组丙氨酸转氨酶(ALT)(140±22) U/L,天冬氨酸转氨酶(AST)(131±16) U/L;激素治疗组ALT(76±11)U/L,AST (71±10) U/L;4-1BBmAb治疗组ALT(98±14) U/L,AST (89±11) U/L;联合治疗组ALT (61±8) U/L,AST (55±7) U/L;联合治疗组与4-1BBmAb组、激素治疗组、健康对照组比较,差异均具有统计学意义(P＜0.01).健康对照组、激素治疗组及4-1BBmAb组CD4+CD25+T细胞分别为(3.0±0.8)％,(8.5±2.9)％及(8.4±3.5)％,而联合治疗组为(11.2±3.5)％,联合治疗组与其他3组比较,差异均有统计学意义(P＜0.05).结论 4-1BBmAb对免疫性肝损伤具有一定的治疗作用.4-1BBmAb联合激素治疗效果比单独使用激素或4-1BBmAb治疗效果更好.4-1BBmAb及激素对CD4+CD25+T细胞表达的影响可能是其治疗作用机制之一.
목적 탐토4-1BB단극륭항체(4-1BBmAb)급격소대면역성간손상적치료작용급대CD4+CD25+T세포적영향.방법 건립도두단백A(ConA)유도면역성간손상소서모형,격소치료조ConA주사2h후복강내주사갑발니룡(3 mg/kg),4-1BBmAb치료조미정맥주사4-1BBmAb(100 μg/지),연합치료조동시사용갑발니룡(3 mg/kg)급4-1BBmAb(100 μg/지),건강대조조부주사상동체적적0.9％록화납주사액.분별통과간장조직학、간공능진행치료효과적험증.분별추취각조소서혈액,류식세포의관찰CD4+CD25+T세포표체적변화.채용방차분석급t검험진행통계분석.결과 건강대조조병안산전안매(ALT)(140±22) U/L,천동안산전안매(AST)(131±16) U/L;격소치료조ALT(76±11)U/L,AST (71±10) U/L;4-1BBmAb치료조ALT(98±14) U/L,AST (89±11) U/L;연합치료조ALT (61±8) U/L,AST (55±7) U/L;연합치료조여4-1BBmAb조、격소치료조、건강대조조비교,차이균구유통계학의의(P＜0.01).건강대조조、격소치료조급4-1BBmAb조CD4+CD25+T세포분별위(3.0±0.8)％,(8.5±2.9)％급(8.4±3.5)％,이연합치료조위(11.2±3.5)％,연합치료조여기타3조비교,차이균유통계학의의(P＜0.05).결론 4-1BBmAb대면역성간손상구유일정적치료작용.4-1BBmAb연합격소치료효과비단독사용격소혹4-1BBmAb치료효과경호.4-1BBmAb급격소대CD4+CD25+T세포표체적영향가능시기치료작용궤제지일.
Objective To investigate the therapeutic effect of 4-1BB monoclonal antibodies (4-1BBmAb) and glucocorticosteroid and the affect of the expression of CD4+CD25+T lymphocytes on the mouse hepatitis induced by ConA.Methods Mouse model of hepatic injury was induced by the application of ConA and checked by hepatic function tests and hepatic pathology.Mter the animal models were constructed,the mice in the group of therapeutic alliance were treated with glucocorticosteroid and 4-1BBmAb.In contrast,mice in the control group were treated with 4-1BBmAb or glucocorticosteroid alone.The groups were then compared.After blood was collected respectively from the control group,the model group and the therapy group,flow cytometry was used to examine CD4+CD25+T lymphocytes.Chi-square test and t-test were used for statistical analysis.Results Compared with the control group,the conditions of the mice were improved after being disposed with 4-1BBmAb.The conditions became even better when 4-1BBmAb were used combined with glucocorticosteroid.ALT and AST of the control group were (140±22) U/L and (131±16) U/L respectively,that of 4-1BBmAb group were (98±14) U/L and (89±11) U/L respectively.The ALT and AST of the glucocorticosteroid treatment group were (76±11) U/L and (71±10) U/L respectively,ALT was (61±8) U/L and AST was (55±7) U/L in the combination treatment group.Differences among groups was statistically significant (P＜0.01).The expression of CD4+CD25+T lymphocytes was (3.0±0.8)％ in the control group,(8.5±2.9)％ in the gluco-corticosteroid treatment group,(8.4±3.5)％ in the 4-1BBmAb treatment group and was (11.2±3.5)％ in the combination treatment group.The difference was significant among the groups (P＜0.05).Conclusion 4-1BB-mAb have therapeutic effect for hepatic injury.The effectiveness will become even more evident when 4-1BB monoclonal antibodies are used together with glucocorticosteroid.During the course of treatment,4-1BBmAb and glucocorticosteroid can impact the expressions of CD4+CD25+T lymphocytes and this is the mechanism for the effectiveness in treating immune-mediated hepatic injury.