Effects of dexmedetomidine at different concentrations on donor kidneys after cardiac death in rats

Abstract

Objective To compare the protective effects of dexmedetomidine (Dex) at different concentrations on donor kidneys from donation after circulatory death (DCD) in rats during static cold storage, and to investigate the appropriate dose of Dex in protection of donor kidneys of DCD. Methods Forty male SD rats were randomly divided into control group (NC group), model group (0 nmol/L Dex) and 6 dosed Dex groups (0.1, 1, 10, 100, 1 000 and 10 000 nmol/L), with 5 animals in each group. All rats were euthanized after anesthetization and intravenous injection of heparin. In 30 min after warm ischemia, renal perfusion was given with normal saline to the rats of the NC group, and with the University of Wisconsin organ preservation solution (UW solution) containing corresponding concentrations of Dex to the rest groups. In the NC group, the kidneys were harvested, fixed directly and stored at -80 ℃. The kidneys of the other groups were harvested after infusion of UW solution containing different concentrations of Dex and then stored in the corresponding preservation solution at 4 ℃ for 24 h to simulate static cold storage of donor kidneys. The morphological changes of renal tissues were observed by light microscopy. The expression levels of Caspase-3 and kidney injury molecule-1 (KIM-1) were determined by immunohistochemical staining. The MDA content, T-SOD activity and NAG level were determined by corresponding reagent kits. The mRNA levels of inflammation-related factors IL-6 and TNF-α were detected by real-time quantitative PCR. Results ① The 0 nmol/L Dex group had significantly increased renal injury score, Caspase-3 and KIM-1 levels, enhanced NAG activity, and elevated MDA content and IL-6 mRNA level, decreased T-SOD activity than the NC group (P < 0.05). ② In comparison with the 0 nmol/L Dex group, the renal injury score was reduced in the 100 and 1 000 nmol/L groups (1.33±0.26 and 1.30±0.16 vs 2.14±0.34, P < 0.05), the expression level of KIM-1 was declined in the 1, 10, 100 and 1 000 nmol/L Dex groups (P < 0.05), NAG activity and Caspase-3 expression were decreased in the 100 and 1 000 nmol/L groups (P < 0.05), decreased MDA content was observed in all dose groups except the 0.1 nmol/L Dex group(P < 0.05), decreased mRNA levels of IL-6 was in all dose groups except the 10 000 nmol/L Dex group(P < 0.05), and declined mRNA levels of TNF-α was seen in all dose groups (P < 0.05). ③Compared with 0.1 nmol/L Dex group, the 100 and 1 000 nmol/L Dex groups had significantly decreased expression level of KIM-1 (0.19±0.01 and 0.18±0.02 vs 0.25±0.02, P < 0.05) and content of MDA (P < 0.05); the 10, 100 and 1 000 nmol/L Dex groups obtained reduced levels of IL-6 and TNF-α (P < 0.05). ④ The level of TNF-α was obviously decreased in the 100 and 1 000 nmol/L Dex groups than the 1 and 10 nmol/L Dex groups (P < 0.05). ⑤ SOD activity was notably enhanced in the 1 000 nmol/L Dex group than the 0, 0.1 and 10 nmol/L Dex groups (P < 0.05). Conclusion Dex shows protective effects on rat DCD donor kidneys in a dose-dependent manner, with the doses of 100 nmol/L and 1 000 nmol/L exerting the optimal effects, which may be due to its reducing apoptosis, inhibiting inflammatory response and anti-oxidative stress.

Keywords

• donation after circulatory death
• dexmedetomidine
• kidney transplantation
• organ protection