Department of Electrical Engineering, Biophotonics Lab, University of Wisconsin Milwaukee, Milwaukee, WI, USA.
Department of Radiation Oncology and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Ann Biomed Eng. 2019 Jul;47(7):1564-1574. doi: 10.1007/s10439-019-02255-8. Epub 2019 Apr 8.
The kidney is one of the most radiosensitive organs; it is the primary dose-limiting organ in radiotherapies for upper abdominal cancers. The role of mitochondrial redox state in the development and treatment of renal radiation injury, however, remains ill-defined. This study utilizes 3D optical cryo-imaging to quantify renal mitochondrial bioenergetics dysfunction after 13 Gy leg-out partial body irradiation (PBI). Furthermore, the mitigating effects of lisinopril (lisino), an anti-hypertensive angiotensin converting enzyme inhibitor, is assessed in renal radiation-induced injuries. Around day 150 post-irradiation, kidneys are harvested for cryo-imaging. The 3D images of the metabolic indices (NADH, nicotinamide adenine dinucleotide, and FAD, flavin adenine dinucleotide) are acquired, and the mitochondrial redox states of the irradiated and irradiated + lisino kidneys are quantified by calculating the volumetric mean redox ratio (NADH/FAD). PBI oxidized renal mitochondrial redox state by 78%. The kidneys from the irradiated + lisino rats showed mitigation of mitochondrial redox state by 93% compared to the PBI group. The study provides evidence for an altered bioenergetics and energy metabolism in the rat model of irradiation-induced kidney damage. In addition, the results suggest that lisinopril mitigates irradiation damage by attenuating the oxidation of mitochondria leading to increase redox ratio.
肾脏是对放射线最敏感的器官之一；它是上腹部癌症放射治疗中主要的剂量限制器官。然而，线粒体氧化还原状态在肾放射损伤的发生和治疗中的作用仍未明确。本研究利用三维光学冷冻成像技术，定量分析 13Gy 下肢外半身照射（PBI）后肾脏线粒体生物能量功能障碍。此外，还评估了抗高血压血管紧张素转换酶抑制剂赖诺普利（lisino）对肾放射损伤的缓解作用。照射后约 150 天，采集肾脏进行冷冻成像。获取代谢指标（NADH、烟酰胺腺嘌呤二核苷酸和 FAD、黄素腺嘌呤二核苷酸）的三维图像，并通过计算体积平均氧化还原比（NADH/FAD）来量化照射和照射+赖诺普利肾脏的线粒体氧化还原状态。PBI 使肾脏线粒体氧化还原状态氧化 78%。与 PBI 组相比，照射+赖诺普利大鼠的肾脏线粒体氧化还原状态减轻了 93%。该研究为照射诱导的肾脏损伤大鼠模型中能量代谢改变提供了证据。此外，结果表明赖诺普利通过减轻线粒体氧化来减轻照射损伤，从而增加氧化还原比。
