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器官移植已成为治疗终末期器官衰竭患者的主要手段,为避免术后排斥反应的发生和发展,患者术后需终生服用大量免疫抑制药物。尽管免疫抑制剂的应用有效地预防了急性排斥反应的发生,但其在实体器官移植患者中仍有引起潜在严重并发症的可能。此外,尽管长期服用免疫抑制药物,大多数移植患者仍会因急性或慢性移植物损伤引起移植器官功能障碍。虽然最初的排斥反应由宿主机体获得性免疫系统中T淋巴细胞引起,但最新证据表明天然免疫系统在移植物排斥反应发展过程中也起着重要作用。天然免疫识别由多个不同蛋白质家族的受体启动,其中包括Toll样受体(TLRs)家族。TLRs能够特异性地识别一系列病原微生物和内源性介质,激活天然免疫系统。TLRs的发现使人们对器官移植术后引起及调节炎症反应的分子机制有了新的认识。TLRs活化可以激活获得性免疫系统,导致移植物的缺血再灌注损伤、急性排斥和慢性排斥反应,同时可通过TLRs诱导免疫耐受。TLRs作为干预治疗的潜在目标开始受到人们青睐。本文总结TLRs和及其配体的结构和功能特点,重点探讨目前在动物实验及临床器官移植中TLRs对缺血再灌注损伤、移植排斥和免疫调节的作用。
Organ transplantation has become the treatment of end-stage organ failure in patients with the main means to avoid the occurrence and development of postoperative rejection, patients need to take a lot of life-long immunosuppressive drugs. Although the application of immunosuppressive agents can effectively prevent the occurrence of acute rejection, they still have the potential to cause potentially serious complications in patients with solid organ transplantation. In addition, most transplant patients can still cause organ dysfunction due to acute or chronic graft injury, despite long-term immunosuppressive drugs. Although the initial rejection was caused by T lymphocytes in the host’s adaptive immune system, recent evidence suggests that the innate immune system also plays an important role in the development of graft rejection. Natural immune recognition is initiated by receptors from a number of different protein families, including the Toll-like receptor (TLRs) family. TLRs specifically recognize a range of pathogenic microorganisms and endogenous mediators, activating the innate immune system. The discovery of TLRs has led to a new understanding of the molecular mechanisms that cause and regulate inflammatory responses after organ transplantation. Activation of TLRs activates the adaptive immune system, resulting in ischemia-reperfusion injury, acute rejection, and chronic rejection of the graft, while inducing immune tolerance via TLRs. TLRs as the potential target of intervention began to be favored by people. This review summarizes the structural and functional characteristics of TLRs and their ligands and focuses on the current role of TLRs in ischemia-reperfusion injury, graft rejection and immune regulation in animal experiments and clinical organ transplantation.