Rho Kinase Inhibitor,Fasudil, Attenuates Contrast‐induced Acute Kidney Injury |
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| Authors: | Yiming Wang Hao Zhang Zhijian Yang Dengshun Miao Dingguo Zhang |
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| Affiliation: | 1. Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China;2. Department of Cardiology, Zhenjiang First People's Hospital, Zhenjiang, China;3. Research Center for Bone and Stem Cells, Nanjing Medical University, Nanjing, China |
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| Abstract: | 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. |
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