Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Cardiology, Zhenjiang First People's Hospital, Zhenjiang, China.
Basic Clin Pharmacol Toxicol. 2018 Feb;122(2):278-287. doi: 10.1111/bcpt.12895. Epub 2017 Sep 19.
In this study, we tested the hypothesis that fasudil, a Rho kinase inhibitor, would protect against contrast-induced acute kidney injury (CI-AKI) in a mouse model and attempted to elucidate the mechanism involved. Mice subjected to unilateral ligation of the left anterior renal pedicle were divided into four groups: (1) control group, (2) CI-AKI induced by contrast media (CM group), (3) CI-AKI plus low-dose fasudil (LD group) and (4) CI-AKI plus high-dose fasudil (HD group). Animals from groups 2-4 received iodixanol (4.0 g iodine/kg), and the control group received saline. At 12, 2 hr before iodixanol injection and 4 hr after iodixanol administration, the animals in groups 3-4 received 3 or 10 mg/kg fasudil, respectively. Renal blood flow, renal function parameters, kidney histology and the expression of proteins that regulates apoptosis and inflammation were determined 24 hr later. Fasudil treatment notably ameliorated contrast medium-induced medullary damage, restored renal function, suppressed renal tubular apoptosis, ameliorated redox imbalance and DNA damage. Fasudil had a nephroprotective effect that was partially attributed to its anti-inflammatory, anti-apoptotic and antioxidant effects of inhibiting the Rho/ROCK pathway.
在这项研究中，我们检验了 Rho 激酶抑制剂法舒地尔可预防对比剂诱导的急性肾损伤（CI-AKI）这一假说，并试图阐明其相关机制。将单侧结扎左肾前肾蒂的小鼠分为四组：（1）对照组，（2）造影剂诱导的 CI-AKI（CM 组），（3）CI-AKI 加低剂量法舒地尔（LD 组）和（4）CI-AKI 加高剂量法舒地尔（HD 组）。组 2-4 的动物接受碘克沙醇（4.0 克碘/千克），对照组给予生理盐水。在注射碘克沙醇前 12 小时、2 小时和注射碘克沙醇后 4 小时，组 3-4 的动物分别接受 3 或 10 mg/kg 法舒地尔。24 小时后测定肾脏血流、肾功能参数、肾脏组织学以及调节细胞凋亡和炎症的蛋白质表达。法舒地尔治疗明显改善了对比剂诱导的皮质损伤，恢复了肾功能，抑制了肾小管细胞凋亡，改善了氧化还原失衡和 DNA 损伤。法舒地尔具有肾脏保护作用，部分归因于其抑制 Rho/ROCK 通路的抗炎、抗凋亡和抗氧化作用。
