Department of Surgery.
Robert M. Berne Cardiovascular Research Center.
Curr Opin Organ Transplant. 2021 Apr 1;26(2):250-257. doi: 10.1097/MOT.0000000000000854.
Primary graft dysfunction (PGD) is the leading cause of early mortality following lung transplantation and is typically caused by lung ischemia-reperfusion injury (IRI). Current management of PGD is largely supportive and there are no approved therapies to prevent lung IRI after transplantation. The purinergic signaling network plays an important role in this sterile inflammatory process, and pharmacologic manipulation of said network is a promising therapeutic strategy. This review will summarize recent findings in this area.
In the past 18 months, our understanding of lung IRI has improved, and it is becoming clear that the purinergic signaling network plays a vital role. Recent works have identified critical components of the purinergic signaling network (Pannexin-1 channels, ectonucleotidases, purinergic P1 and P2 receptors) involved in inflammation in a number of pathologic states including lung IRI. In addition, a functionally-related calcium channel, the transient receptor potential vanilloid type 4 (TRPV4) channel, has recently been linked to purinergic signaling and has also been shown to mediate lung IRI.
Agents targeting components of the purinergic signaling network are promising potential therapeutics to limit inflammation associated with lung IRI and thus decrease the risk of developing PGD.
原发性移植物功能障碍（PGD）是肺移植后早期死亡的主要原因，通常由肺缺血再灌注损伤（IRI）引起。目前对 PGD 的治疗主要是支持性的，没有经过批准的疗法可以预防移植后肺 IRI。嘌呤能信号网络在这个无菌性炎症过程中起着重要作用，对该网络的药物干预是一种很有前途的治疗策略。这篇综述将总结该领域的最新发现。
在过去的 18 个月里，我们对肺 IRI 的认识有所提高，很明显嘌呤能信号网络起着至关重要的作用。最近的研究确定了嘌呤能信号网络（Pannexin-1 通道、核苷酸酶、嘌呤 P1 和 P2 受体）中的关键组成部分，这些组成部分参与了包括肺 IRI 在内的许多病理状态下的炎症。此外，最近发现一种功能相关的钙通道，瞬时受体电位香草酸型 4（TRPV4）通道，与嘌呤能信号有关，也被证明介导肺 IRI。
针对嘌呤能信号网络成分的药物是很有前途的潜在治疗方法，可以限制与肺 IRI 相关的炎症，从而降低发生 PGD 的风险。
