辅酶Q10对雄性糖尿病大鼠造影剂诱导的急性肾损伤的保护作用。
Protection of coenzyme Q10 against contrast-induced acute kidney injury in male diabetic rats.
作者信息
Couto Sheila Marques Fernandes, da Fonseca Cassiane Dezoti, Watanabe Mirian, de Fátima Fernandes Vattimo Maria
机构信息
Laboratório Experimental de Modelos Animais (LEMA), Escola de Enfermagem da Universidade de São Paulo (EEUSP), Avenida Doutor Enéas de Carvalho Aguiar, 419, Cerqueira César, São Paulo, SP, 05403-000, Brazil.
Escola Paulista de Enfermagem da Universidade Federal de São Paulo, São Paulo, SP, Brazil.
出版信息
Diabetol Metab Syndr. 2021 Jun 16;13(1):69. doi: 10.1186/s13098-021-00689-6.
BACKGROUND
Diabetes mellitus (DM) is a major risk factor for contrast-induced acute kidney injury (CI-AKI). DM and CI-AKI result in oxidative damage and inflammation that can be reduced when treated with the coenzyme Q-10 (CoQ10). The aim of this study was to investigate the therapeutic potential of CoQ10 in renal function, renal hemodynamics, oxidative profile and renal histology in diabetic rats subjected to CI-AKI.
METHODS
Wistar rats, male, randomized into five groups: citrate: control animals received citrate buffer (streptozotocin vehicle, 0.4 mL); Tween: control animals of CoQ10 treatment received 1% Tween 80 (CoQ10 vehicle, 0.5 mL); DM: animals that received streptozotocin (60 mg/kg); DM + IC: DM animals treated with iodinated contrast (IC, 6 mL/kg); DM + IC + CoQ10: DM animals treated with CoQ10 (10 mg/kg) and that received IC (6 mL/kg). The protocols lasted 4 weeks. An evaluation was made to measure renal function, inulin clearance and serum creatinine, renal hemodynamics by renal blood flow (RBF) and renal vascular resistance (RVR), markers of oxidative stress such as urinary peroxides and nitrate, lipid peroxidation, thiols in renal tissue and renal histological analysis.
RESULTS
DM animals showed reduced renal function, which was followed by an increase inserum creatinine and significant reduction of inulin clearance and RBF. It was noticed an increase in RVR and redox imbalance with higher urinary peroxides and nitrate lipid peroxidation levels with depletion of thiols in renal tissue. IC treatment exacerbated these changes in DM + IC. CoQ10 administration ameliorated renal function, prevented hemodynamic changes and neutralized oxidative damage and progression of the histologic damage in the DM + IC + CoQ10 group.
CONCLUSION
This study demonstrated the renoprotection properties of CoQ10 in an experimental model of risk factor of DM for CI-AKI. CoQ10 presented an antioxidant effect on the CI-AKI in male diabetic rats by improving renal function and renal hemodynamics, preserving morphology and reducing oxidative stress.
背景
糖尿病（DM）是造影剂诱导的急性肾损伤（CI-AKI）的主要危险因素。糖尿病和造影剂诱导的急性肾损伤会导致氧化损伤和炎症，而使用辅酶Q-10（CoQ10）治疗时这些损伤可减轻。本研究的目的是探讨CoQ10对接受CI-AKI的糖尿病大鼠肾功能、肾血流动力学、氧化状态及肾脏组织学的治疗潜力。
方法
将雄性Wistar大鼠随机分为五组：柠檬酸盐组：对照动物接受柠檬酸盐缓冲液（链脲佐菌素溶媒，0.4 mL）；吐温组：CoQ10治疗的对照动物接受1%吐温80（CoQ10溶媒，0.5 mL）；糖尿病组：接受链脲佐菌素（60 mg/kg）的动物；糖尿病+碘造影剂组：用碘化造影剂（IC，6 mL/kg）治疗的糖尿病动物；糖尿病+碘造影剂+CoQ10组：用CoQ10（10 mg/kg）治疗且接受碘造影剂（6 mL/kg）的糖尿病动物。实验方案持续4周。对肾功能、菊粉清除率和血清肌酐进行评估，通过肾血流量（RBF）和肾血管阻力（RVR）评估肾血流动力学，通过尿过氧化物和硝酸盐、脂质过氧化、肾组织中的硫醇等氧化应激标志物以及肾脏组织学分析进行评估。
结果
糖尿病动物肾功能降低，随后血清肌酐升高，菊粉清除率和肾血流量显著降低。观察到肾血管阻力增加以及氧化还原失衡，尿过氧化物和硝酸盐脂质过氧化水平升高，肾组织中硫醇减少。碘造影剂治疗加剧了糖尿病+碘造影剂组的这些变化。在糖尿病+碘造影剂+CoQ10组中，给予CoQ10可改善肾功能，预防血流动力学变化，并中和氧化损伤以及组织学损伤的进展。
结论
本研究在糖尿病作为CI-AKI危险因素的实验模型中证明了CoQ10的肾脏保护特性。CoQ10通过改善肾功能和肾血流动力学、保持形态并减少氧化应激，对雄性糖尿病大鼠的CI-AKI呈现抗氧化作用。
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