Yin Jianyong, Chen Weibin, Ma Fenfen, Lu Zeyuan, Wu Rui, Zhang Guangyuan, Wang Niansong, Wang Feng
Department of Nephrology, Shanghai Eighth People's Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Department of Laboratory Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Oncotarget. 2017 Feb 7;8(6):9986-9995. doi: 10.18632/oncotarget.14309.
Sulodexide is a potent antithrombin agent, however, whether it has beneficial effects on renal ischemia-reperfusion injury (IRI) remains unknown. In the present study, we assessed the therapeutic effects of sulodexide in renal IRI and tried to investigate the potential mechanism. One dose of sulodexide was injected intravenously in Sprague-Dawley rats 30 min before bilateral kidney ischemia for 45 min. The animals were sacrificed at 3h and 24h respectively. Our results showed that sulodexide pretreatment improved renal dysfunction and alleviated tubular pathological injury at 24h after reperfusion, which was accompanied with inhibition of oxidative stress, inflammation and cell apoptosis. Moreover, we noticed that antithrombin III (ATIII) was activated at 3h after reperfusion, which preceded the alleviation of renal injury. For in vitro study, hypoxia/reoxygenation (H/R) injury model for HK2 cells was carried out and apoptosis and reactive oxygen species (ROS) levels were evaluated after sulodexide pretreatment. Consistently, sulodexide pretreatment could reduce apoptosis and ROS level in HK2 cells under H/R injury. Taken together, sulodexide pretreatment might attenuate renal IRI through inhibition of inflammation, oxidative stress and apoptosis, and activation of ATIII.
舒洛地昔是一种强效抗凝血酶药物,然而,其对肾缺血再灌注损伤(IRI)是否具有有益作用仍不清楚。在本研究中,我们评估了舒洛地昔对肾IRI的治疗效果,并试图探究其潜在机制。在双侧肾脏缺血45分钟前30分钟,给Sprague-Dawley大鼠静脉注射一剂舒洛地昔。分别在3小时和24小时处死动物。我们的结果显示,舒洛地昔预处理改善了再灌注后24小时的肾功能障碍并减轻了肾小管病理损伤,这伴随着氧化应激、炎症和细胞凋亡的抑制。此外,我们注意到再灌注后3小时抗凝血酶III(ATIII)被激活,这发生在肾损伤减轻之前。对于体外研究,建立了HK2细胞的缺氧/复氧(H/R)损伤模型,并在舒洛地昔预处理后评估细胞凋亡和活性氧(ROS)水平。一致地,舒洛地昔预处理可降低H/R损伤下HK2细胞的凋亡和ROS水平。综上所述,舒洛地昔预处理可能通过抑制炎症、氧化应激和凋亡以及激活ATIII来减轻肾IRI。