Immunosuppressive activity of the Chinese medicinal plant Tripterygium wilfordii -: II.: Prolongation of hamster-to-rat cardiac xenograft survival by combination therapy with the PG27 extract and cyclosporine
Immunosuppressive activity of the Chinese medicinal plant Tripterygium wilfordii -: II.: Prolongation of hamster-to-rat cardiac xenograft survival by combination therapy with the PG27 extract and cyclosporine
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DOI：
10.1097/00007890-200008150-00011
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发表时间：
2000-08-15
期刊：
影响因子：
6.2
通讯作者：
Fidler, JM
中科院分区：
文献类型：
--
作者：
Wang, J;Xu, RS;Fidler, JM
背景PG 27是从中药雷公藤提取物中纯化的免疫抑制组分，我们在仓鼠-大鼠心脏异种移植模型中单独和联合环孢素（CsA）研究了PG 27。将金黄地鼠心脏异位移植于刘易斯大鼠腹部，分别经腹腔注射或口服PG 27、CsA或两者联合应用。30 mg/kg/天PG 27和10 mg/kg/天CsA的联合治疗成功抑制了仓鼠-大鼠心脏异种移植物急性排斥反应。PG 27或CsA单独治疗无效，在几种有效的组合中，最佳方案为PG 27 30 mg/kg/d + CsA 5 mg/kg/d，从第8天至第35天，然后CsA 5 mg/kg/d，从第36天至第100天，其在100天后的存活率为100%。CsA抑制异源特异性淋巴细胞毒性抗体反应，并抑制IgG但不抑制IgM异种抗体产生（导致异种移植排斥反应），而PG 27单独不能阻止抗体产生。PG 27/CsA联合应用可阻断异种心脏移植诱导的淋巴细胞毒性抗体反应和IgG、IgM异种抗体的产生。结论：PG 27联合CsA可显著延长仓鼠-大鼠异种心脏移植物的存活时间，并可完全抑制异种抗体的产生。
Background. PG27 is an immunosuppressive fraction purified from an extract of a Chinese medicinal plant Tripterygium wilfordii, which we investigated alone and in combination with cyclosporine (CsA) in a concordant, hamster-to-rat cardiac xenotransplantation model.Methods. Golden Syrian hamster hearts were heterotopically transplanted into the abdomen of Lewis rat recipients, which were treated intraperitoneally or orally with PG27, CsA, or both.Results. Combination therapy with 30 mg/kg/day of PG27 and CsA at 10 mg/kg/day successfully suppressed acute hamster-to-rat cardiac xenograft rejection. Treatment with PG27 or CsA alone was ineffective, Among several effective combinations, the best regimen involved PG27 at 30 mg/kg/day and CsA at 5 mg/kg/day from days 8 to 35 and then CsA at 5 mg/kg/day from days 36 to 100, which produced 100% survival beyond 100 days, CsA suppressed the heterospecific lymphocytotoxic antibody response and inhibited IgG but not IgM xenoantibody production (which led to xenograft rejection), whereas PG27 alone did not prevent antibody production. The PG27/CsA combination blocked the lymphocytotoxic antibody response and IgG and IgM xenoantibody production induced by cardiac xenotransplantation,Conclusions, PG27 combined with CsA substantially prolonged hamster-to-rat cardiac xenograft survival, as well as completely inhibiting xenoantibody production.