Kurahara Natsume, Yutsudo Ayami, Yamato Osamu, Miyoshi Noriaki, Hifumi Tatsuro, Yabuki Akira
Laboratory of Veterinary Clinical Pathology, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
Laboratory of Veterinary Histopathology, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
J Vet Med Sci. 2025 Mar 1;87(3):248-256. doi: 10.1292/jvms.24-0296. Epub 2025 Jan 22.
Apoptosis, an important pathological event associated with kidney disease progression, is expected to be a therapeutic target in chronic kidney disease (CKD). However, its role in naturally occurring CKD in aged cats remains unclear. Therefore, here, we investigated kidney tissues from aged cats (≥10 years) with or without azotemic CKD to evaluate apoptotic events using a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. The positive TUNEL signals of the renal cells were quantified and statistically analyzed for correlation with the severity of plasma creatinine (pCre) concentration, renal lesions (glomerulosclerosis, interstitial cell infiltration, peritubular capillaries, and interstitial fibrosis), and oxidative damage of the kidney tissue. Oxidative damage was evaluated using immunohistochemistry for 8-hydroxy-2'-deoxyguanosine (OHdG) and 4-hydroxynonenal (HNE). In the TUNEL assay, regardless of azotemia, positive nuclear signals were observed in the tubular epithelial and intraluminal cells, interstitial infiltrating cells, and glomerular cells. Quantitative TUNEL scores showed no significant differences between the azotemic and non-azotemic groups in any compartment of the kidney tissues. In the azotemic group, TUNEL scores did not correlate with pCre or renal lesion severity. However, the scores showed a significant positive correlation with the scores of 8-OHdG and 4-HNE. These findings suggest that apoptosis associated with oxidative damage in renal tissue is an initial pathological event that leads to CKD, rather than a change following CKD progression, in aged cats. Inhibiting apoptosis by antioxidant treatment may be a key strategy to prevent the development of CKD.
细胞凋亡是与肾脏疾病进展相关的重要病理事件，有望成为慢性肾脏病（CKD）的治疗靶点。然而，其在老年猫自然发生的CKD中的作用仍不清楚。因此，在此我们研究了患有或未患有氮质血症性CKD的老年猫（≥10岁）的肾脏组织，使用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记（TUNEL）法评估细胞凋亡事件。对肾细胞的TUNEL阳性信号进行定量，并进行统计分析，以确定其与血浆肌酐（pCre）浓度、肾脏病变（肾小球硬化、间质细胞浸润、肾小管周围毛细血管和间质纤维化）以及肾脏组织氧化损伤的严重程度之间的相关性。使用针对8-羟基-2'-脱氧鸟苷（OHdG）和4-羟基壬烯醛（HNE）的免疫组织化学评估氧化损伤。在TUNEL试验中，无论是否存在氮质血症，在肾小管上皮细胞和管腔内细胞、间质浸润细胞和肾小球细胞中均观察到阳性核信号。定量TUNEL评分显示，在肾脏组织的任何区域，氮质血症组和非氮质血症组之间均无显著差异。在氮质血症组中，TUNEL评分与pCre或肾脏病变严重程度无关。然而，这些评分与8-OHdG和4-HNE的评分呈显著正相关。这些发现表明，在老年猫中，与肾脏组织氧化损伤相关的细胞凋亡是导致CKD的初始病理事件，而非CKD进展后的变化。通过抗氧化治疗抑制细胞凋亡可能是预防CKD发生的关键策略。
