AG490延长移植心存活时间的探讨

目的 研究AG490在大鼠心脏移植中免疫抑制及延长移植心存活时间的作用,探讨AG490的作用机制.方法 供者为SD大鼠,受者为Wistar大鼠,建立大鼠心脏移植模型.将受者分为4组.对照组(14只):术后1～7 d经尾静脉注射生理盐水0.2 ml·kg-1·d-1;AG490组(14只):术后1～7 d经尾静脉注射AG490 20 mg·kg-1·d-1;CsA组(10只):术后1～7 d经尾静脉注射CsA20 mg·kg-1·d-1;AG490+CsA组(10只):术后1～7 d经尾静脉注射AG490和CsA各20mg·kg-1·d-1.术后各组分别取10只受者,观察移植心存活时间,并在术后1、4和7 d时,检测受者外周血中白细胞介素(IL)-2和IL-6的水平.术后第7天,处死对照组和AG490组受者(各4只)后,分别取移植心组织进行病理学检测.结果 AG490组受者术后移植心存活时间为(26.6±3.81)d,CsA组为(28.4±4.25)d,AG490+CsA组为(31.8±4.39)d,均较对照组的(8.4±0.84)d显著延长(P＜0.05).与对照组相比,AG490组术后外周血IL-2水平显著降低(P＜0.05),IL-6水平虽有所降低,但差异无统计学意义(P＞0.05),而AG490+CsA组IL-2和IL-6水平下降更为显著,与对照组相比,差异均有统计学意义(P＜0.05).AG490组移植心组织中淋巴细胞浸润程度较对照组明显减轻.结论 AG490具有免疫抑制作用,能延长移植物的存活时间,与CsA联合应用时效果更加明显.AG490的主要作用机制包括降低IL-2表达的水平,抑制移植心组织中淋巴细胞的浸润.

The effects of AG490 on the outcome of mouse heart transplantation

Objective To evaluate the possibility and prospect of the AG490 as a potential immunosuppressor in the rat model of heart transplantation. Methods The rat model of heart transplantation was established. All recipients (Wistar rats) were divided into 4 groups: cyclosporine group (n = 10), AG490 group (n = 14), CsA + AG490 group (n = 10), control group (n = 14). Cyclosporine (20 mg.kg-1·d-1), AG490 (20 mg·kg-1.d-1) or sodium chloride (0.2 ml-kg-1·d-1) was intraperitoneally injected for 7 days. The graft survival time, the levels of IL-2 and IL-6, mononuclear cell infiltration on the day 1, 4, 7 were. Four recipients in control group and AG490 group were killed at 7th day and the graft tissue was pathologically examined. Results The graft survival time in AG490 group (26.6±3.81 )days, cyclosporine group (28.4±4.25)days, CsA + AG490 group (31.8±4.39) days was longer than in control group (8.4±0.84)days (P＜0.05). The levels of IL-2 in AG490 group were lower than in control group (P＜0.05), hut there was no significant difference in the level of IL-6 between them (P＜0.05). In CsA + AG490 group, the levels of IL-2 and IL-6 were lower than in control group (P＜0.05). The mononuclear cell infiltration in graft in AG490 group was decreased as compared with control group. Conclusions AG490 can display the immunosuppressive effects, prolong the graft survival time, and the combined use of AG490 and cyclosporine has synergetic effects.The main action mechanism of AC-490 is the decreased expression of IL-2 and inhibition of mononuclear cell infiltration.