PDF(Pubmed)
Abstract：
Lung ischemia-reperfusion injury (LIRI) is a prevalent occurrence in various pulmonary diseases and surgical procedures, including lung resections and transplantation. LIRI can result in systemic hypoxemia and multi-organ failure. Hydroxycitric acid (HCA), the primary acid present in the peel of Garcinia cambogia, exhibits anti-inflammatory, antioxidant, and anticancer properties. However, the effects of HCA on LIRI remain unknown. To investigate the impact of HCA on LIRI in mice, the mice were randomly divided into four groups: the control group, the I/R model group, and the I/R + low- or high-dose HCA groups. Human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia for 12 h followed by reoxygenation for 6 h to simulate in vitro LIRI. The results demonstrated that administration of HCA effectively attenuated lung injury, inflammation, and edema induced by ischemia reperfusion. Moreover, HCA treatment significantly reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels while decreasing iron content and increasing superoxide dismutase (SOD) levels after ischemia-reperfusion insult. Mechanistically, HCA administration significantly inhibited Hif-1α and HO-1 upregulation both in vivo and in vitro. We found that HCA could also alleviate endothelial barrier damage in H/R-induced HUVECs in a concentration-dependent manner. In addition, overexpression of Hif-1α counteracted HCA-mediated inhibition of H/R-induced endothelial cell ferroptosis. In summary, these results indicate that HCA alleviated LIRI by inhibiting oxidative stress and ferroptosis through the Hif-1α pathway.
摘要：
肺缺血再灌注损伤(LIRI)是多种肺部疾病和外科手术中普遍存在的,包括肺切除和移植.LIRI可导致全身低氧血症和多器官衰竭。羟基柠檬酸(HCA),藤黄果皮中存在的主要酸，表现出抗炎，抗氧化剂，和抗癌特性。然而,HCA对LIRI的影响尚不清楚。为了研究HCA对小鼠LIRI的影响，将小鼠随机分为4组:对照组,I/R模型组，I/R+低剂量或高剂量HCA组。将人脐静脉内皮细胞（HUVEC）缺氧12小时，然后复氧6小时以模拟体外LIRI。结果表明，给予HCA可有效减轻肺损伤，炎症,缺血再灌注引起的水肿。此外，缺血再灌注损伤后，HCA治疗可显着降低丙二醛（MDA）和活性氧（ROS）水平，同时降低铁含量并增加超氧化物歧化酶（SOD）水平。机械上,HCA给药在体内和体外均显着抑制了Hif-1α和HO-1的上调。我们发现HCA还可以以浓度依赖的方式减轻H/R诱导的HUVECs中的内皮屏障损伤。此外,Hif-1α的过表达抵消了HCA介导的H/R诱导的内皮细胞铁凋亡的抑制。总之,这些结果表明，HCA通过Hif-1α途径抑制氧化应激和铁凋亡，减轻了LIRI。
