雷帕鸣的作用及功效

Rapamin (sirolimus) inhibits the activation and proliferation of T lymphocytes stimulated by antigens and cytokines (interleukins IL-2, IL-4 and IL-15) through a completely different mechanism of action from other immunosuppressants. Rapamin also inhibits the production of antibodies. In cells, sirolimus binds to the immunophilin FK-binding protein-12 (FKBP-12) to form an immunosuppressive complex. This sirolimus FKBP-12 complex has no effect on calcineurin activity. This complex binds to the mammalian sirolimus target molecule (mTOR, a key regulatory kinase) and inhibits its activity. This inhibition blocks cytokine-driven T cell proliferation, that is, inhibits the progression from the G1 phase to the S phase of the cell cycle.

To evaluate the efficacy and safety of sirolimus in preventing organ rejection after kidney transplantation, two randomized, double-blind, multicenter controlled trials were conducted. Trial 1 was conducted at 38 research sites in the United States, with 719 patients participating. Randomly assigned after transplantation: 284 patients received 2 mg/day of this drug, 274 patients received 5 mg/day of this drug, and 161 patients received azathioprine 2-3 mg/kg/day. Trial 2 was conducted at 34 research units in Australia, Canada, Europe and the United States, with 576 patients participating. Randomly assigned before transplantation: 227 patients received 2 mg/day of this drug, 219 patients received 5 mg/day of this drug, and 130 patients received placebo. In both trials, antilymphocyte antibody induction therapy was contraindicated. In both trials, the primary efficacy endpoint was treatment failure rate within the first 6 months after transplantation. Treatment failure was defined as the first episode of acute rejection (biopsy-confirmed), graft loss, or death.