Kinoshita Yoshitaka, Shirakawa Kohsuke, Sano Motoaki, Yokoo Takashi, Kume Haruki, Kobayashi Eiji
Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Transl Androl Urol. 2022 Apr;11(4):430-438. doi: 10.21037/tau-21-1164.
Acute kidney injury and its central pathology, renal ischemia reperfusion injury (IRI), have been studied in many animal models. Although renal IRI has been induced in pig models in many ways, simultaneous bilateral ischemia or unilateral ischemia along with contralateral nephrectomy models only provide data on the renal response to a single ischemia time. Moreover, it has been reported that prolonged renal ischemia time in pigs for 120 min or more can cause irreversible renal damage and increase animal mortality.
We developed a model that induces prolonged ischemia time and subsequent reperfusion injury without threatening the lives of pigs by subjecting the left and right kidneys to ischemia for 120 and 60 min, respectively. Using this novel model, we investigated whether hydrogen gas inhalation could alleviate renal IRI.
All animals (n=4) survived until the end of the observation period of 3 months in this model. Evaluation of the left and right kidneys immediately before and after IRI could be performed separately by blood sampling from each renal vein and renal biopsy during surgery, although the results of peripheral blood sampling during the follow-up were the mixed results of bilateral kidneys. The release of degraded DNA from the kidneys immediately after IRI and subsequent renal fibrosis at 3 months increased in response to ischemia time. Although the effect of hydrogen gas on pathological findings was not obvious, the release of degraded DNA from the kidney, an acute marker of IRI, appeared to be suppressed.
We have developed a novel model in which IRI of different ischemia times is induced in the bilateral kidney that provides two-fold information and allows for safe long-term observation experiments in pigs. Using this model, hydrogen gas inhalation appeared to reduce acute renal IRI, although the effect was not statistically significant.
急性肾损伤及其核心病理——肾缺血再灌注损伤（IRI），已在许多动物模型中得到研究。尽管肾IRI在猪模型中已通过多种方式诱导产生，但双侧同时缺血或单侧缺血并联合对侧肾切除术模型仅能提供肾脏对单次缺血时间的反应数据。此外，据报道，猪的肾缺血时间延长至120分钟或更长时间会导致不可逆的肾损伤并增加动物死亡率。
我们开发了一种模型，通过分别使左右肾缺血120分钟和60分钟，诱导出延长的缺血时间及随后的再灌注损伤，且不会危及猪的生命。利用这个新模型，我们研究了吸入氢气是否能减轻肾IRI。
在该模型中，所有动物（n = 4）均存活至3个月的观察期结束。在手术期间，通过从每条肾静脉采血和肾活检，可以分别对IRI前后的左右肾进行评估，尽管随访期间外周血采样的结果是双侧肾脏的混合结果。IRI后立即从肾脏释放的降解DNA以及3个月时随后出现的肾纤维化随着缺血时间的增加而增加。尽管氢气对病理结果的影响不明显，但作为IRI急性标志物的肾脏降解DNA的释放似乎受到了抑制。
我们开发了一种新模型，在双侧肾脏中诱导不同缺血时间的IRI，该模型提供了双重信息，并允许在猪身上进行安全的长期观察实验。使用该模型，吸入氢气似乎能减轻急性肾IRI，尽管效果无统计学意义。
