Xie Yingli, Zhao Di, Dong Pingshuan, Lai Lihong
First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471000, China.
First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471000, China
Biosci Rep. 2018 Feb 12. doi: 10.1042/BSR20171734.
Macrophages play essential roles in the generation and resolution of inflammation. Ischemia-reperfusion injury (IRI) triggers a systemic inflammatory response and leads to cellular injury and organ failure. During surgical procedures of the liver, such as hepatic resection and liver transplantation, IRI leads to the dysfunction of the liver. Rho-associated protein kinase (ROCK) inhibitors were reported protecting the liver from IRI. However, the systematic administration of ROCK inhibitors causes severe hypotension. Here, using Fasudil carried liposomes, we specifically inhibited the ROCK-II expression in Kupffer cells and blood monocytes. Through this macrophage/monocyte specific treatment of Fasudil, we successfully protected the liver from IRI by shifting Kupffer cells/monocytes from M1/classical to M2/patrolling phenotype in the liver and peripheral blood. Our finding provides novel insights into the macrophage/monocyte-specific drug delivery and the treatment of liver IRI.
巨噬细胞在炎症的发生和消退过程中发挥着重要作用。缺血再灌注损伤（IRI）会引发全身炎症反应，并导致细胞损伤和器官衰竭。在肝脏手术过程中，如肝切除和肝移植，IRI会导致肝功能障碍。据报道，Rho相关蛋白激酶（ROCK）抑制剂可保护肝脏免受IRI损伤。然而，系统性给予ROCK抑制剂会导致严重低血压。在此，我们使用携带法舒地尔的脂质体，特异性抑制库普弗细胞和血液单核细胞中的ROCK-II表达。通过这种对法舒地尔的巨噬细胞/单核细胞特异性治疗，我们成功地通过将肝脏和外周血中的库普弗细胞/单核细胞从M1/经典表型转变为M2/巡逻表型，保护肝脏免受IRI损伤。我们的发现为巨噬细胞/单核细胞特异性药物递送和肝IRI治疗提供了新的见解。
