Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA; Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
EBioMedicine. 2017 Mar;17:101-107. doi: 10.1016/j.ebiom.2017.02.009. Epub 2017 Feb 12.
We previously reported that insufficiency of antithrombin III (ATIII), the major anti-coagulation molecule in vivo, exacerbated renal ischemia-reperfusion injury in animal models and possibly humans. In the present study, we investigated the relationship between ATIII level and contrast induced nephropathy (CIN) in patients and examined therapeutic effect of ATIII on CIN in Sprague-Dawley rats. Patients with low ATIII activity presented a higher incidence of acute kidney injury (AKI) following coronary angiography. ATIII (500μg/kg) was intravenously injected before or after the induction of AKI in rats. Our data demonstrated ATIII significantly attenuated the elevation of serum creatinine, blood urea nitrogen, and renal histological injury. The beneficial effects of ATIII were accompanied by diminished renal inflammatory response, oxidative stress, cell apoptosis and improved renal blood flow in rats. In conclusion, ATIII appears to attenuate CIN through inhibiting inflammation, oxidative stress, apoptosis and improving renal blood flow. ATIII administration may represent a promising strategy for the prevention and treatment of contrast-induced AKI.
我们之前的报告表明，抗凝血酶 III（ATIII）不足，即体内主要的抗凝分子，会加重动物模型和可能的人类的肾缺血再灌注损伤。在本研究中，我们研究了 ATIII 水平与造影剂肾病（CIN）在患者之间的关系，并检验了 ATIII 对 Sprague-Dawley 大鼠 CIN 的治疗效果。ATIII 活性低的患者在接受冠状动脉造影后发生急性肾损伤（AKI）的几率更高。在诱导大鼠 AKI 之前或之后，将 ATIII（500μg/kg）静脉注射。我们的数据表明，ATIII 显著降低了血清肌酐、血尿素氮和肾组织损伤的升高。在大鼠中，ATIII 的有益作用伴随着肾炎症反应、氧化应激、细胞凋亡的减少和肾血流量的改善。总之，ATIII 通过抑制炎症、氧化应激、细胞凋亡和改善肾血流量来减轻 CIN。ATIII 的给药可能代表了预防和治疗造影剂诱导的 AKI 的一种有前途的策略。
