Application of Fasudil in the Treatment of Contrast-Induced Acute Renal Insufficiency Based on Computerized Tomography Intelligent information monitoring (Preprint)

Abstract

Background: Contrast-induced acute kidney injury (CI-AKI) is one of the main causes of hospital-acquired acute kidney failure. At present, the exact pathogenesis of CI-AKI is not yet clear. However, the contrast agent reduces renal blood flow and filtration rate, which is its direct toxic effect on renal tubules. Fasudil can relax vascular smooth muscle and act on the kidney, which has a very obvious effect on the expansion of the renal arterioles; also, by adjusting the vascular tone of the microcirculation before and after the glomerulus, it can regulate renal hemodynamics.

Objective: The objective was to explore the application of Fasudil in the treatment of contrast-induced acute renal insufficiency based on computerized tomography intelligent information monitoring, and explore the application of single-photon emission computerized tomography (SPECT) in the diagnosis of renal insufficiency.

Methods: 32 BALB/C mice were randomly divided into 4 groups, i.e., the renal disease model group (the model group), the renal disease model plus Fasudil high dosage group (the Fasudil high group), the renal disease model plus Fasudil low dosage group (the Fasudil low group), and the control group. After the mice models were grouped, they were banned from drinking water for 12 h. Mice in the model group, the Fasudil high group, and the Fasudil low group were injected with iodixanol injections at a dosage of 4 gI/kg through caudal veins. Mice in the control group were injected with the same dosage of saline. Respectively at 12 h and 2 h before contrast agent injection and 4 h after contrast agent injection, mice in the two Fasudil groups were administered with Fasudil through intraperitoneal injections. The dosage for the Fasudil high group was 10 mg/kg, and the dosage for the Fasudil low group was 10 mg/kg. At the same time nodes, mice in the model group were administered with the same dosage of saline. The histopathological changes in renal tissues, the variations in renal functions, as well as the changes in renal hemodynamics, were observed.

Results: (1) Compared with the control group, in the model group, the serum creatinine (Cr) and blood urea nitrogen (BUN), as well as the urine N-acetyl-β-D-glucosaminidase (NAG) levels, increased significantly (P<0.05). Compared with the model group, in the Fasudil high group, the serum Cr and BUN, as well as the urine NAG levels, increased significantly (P<0.05). (2) After high-dose fasudil intervention treatment, the destruction of kidney structure in mice was significantly reduced, and the condition of renal tubular epithelial cells swelling was improved. (3) Compared with the control group, in the model group, the RABF values of mice decreased significantly (P<0.05). In the high Fasudil group, after the intervention of high dosed Fasudil, the RABF values of mice increased significantly (P<0.05).

Conclusion: The therapy of high-dosage Fasudil for acute renal damages of mice induced by contrast agents could effectively reduce the serum Cr, serum BUN, and urine NAG levels and act as an anti-apoptotic and anti-infective agent. In addition, Fasudil could resist the oxidative stress, thereby improving the contrast agent-induced vasoconstriction responses. The special functional imaging of SPECT can objectively reflect the function of living organs.