Department of Pediatrics, Chi Mei Medical Center, Tainan, Taiwan.
Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Mediators Inflamm. 2021 Oct 21;2021:1180543. doi: 10.1155/2021/1180543. eCollection 2021.
The Tn antigen, an N-acetylgalactosamine structure linked to serine or threonine, has been shown to induce high-specificity, high-affinity anti-Tn antibodies in mice. Maternal immunization with the Tn vaccine increases serum anti-Tn antibody titers and attenuates hyperoxia-induced kidney injury in neonatal rats. However, immunizing mothers to treat neonatal kidney disease is clinically impractical. This study is aimed at determining whether anti-Tn monoclonal antibody treatment ameliorates hyperoxia-induced kidney injury in neonatal mice. Newborn BALB/c mice were exposed to room air (RA) or normobaric hyperoxia (85% O) for 1 week. On postnatal days 2, 4, and 6, the mice were injected intraperitoneally with PBS alone or with anti-Tn monoclonal antibodies at 25 g/g body weight in 50 L phosphate-buffered saline (PBS). The mice were divided into four study groups: RA + PBS, RA + anti-Tn monoclonal antibody, O + PBS, and O + anti-Tn monoclonal antibody. The kidneys were excised for histology, oxidative stress, cytokine, and Western blot analyses on postnatal day 7. The O + PBS mice exhibited significantly higher kidney injury scores, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nuclear factor-B (NF-B) expression, and cytokine levels than did the RA + PBS mice or RA + anti-Tn mice. Anti-Tn monoclonal antibody treatment reduced kidney injury and cytokine levels to normoxic levels. The attenuation of kidney injury was accompanied by a reduction of oxidative stress and NF-B expression. Therefore, we propose that anti-Tn monoclonal antibody treatment ameliorates hyperoxia-induced kidney injury by suppressing oxidative stress and inflammation in neonatal mice.
Tn 抗原是一种与丝氨酸或苏氨酸相连的 N-乙酰半乳糖胺结构，已被证明能在小鼠中诱导高特异性、高亲和力的抗 Tn 抗体。用 Tn 疫苗对母体进行免疫接种会增加血清抗 Tn 抗体滴度，并减轻新生大鼠高氧诱导的肾损伤。然而，用免疫母体来治疗新生儿肾病在临床上是不切实际的。本研究旨在确定抗 Tn 单克隆抗体治疗是否能改善新生小鼠的高氧诱导肾损伤。新生 BALB/c 小鼠在常氧（RA）或常压高氧（85% O）中暴露 1 周。在出生后第 2、4 和 6 天，小鼠经腹腔注射 PBS 或 25μg/g 体重的抗 Tn 单克隆抗体 50μL。将小鼠分为四组：RA+PBS、RA+抗 Tn 单克隆抗体、O+PBS 和 O+抗 Tn 单克隆抗体。在出生后第 7 天，取出肾脏进行组织学、氧化应激、细胞因子和 Western blot 分析。与 RA+PBS 组或 RA+抗 Tn 组相比，O+PBS 组的小鼠肾脏损伤评分、8-羟基-2'-脱氧鸟苷（8-OHdG）和核因子-B（NF-B）表达以及细胞因子水平显著升高。抗 Tn 单克隆抗体治疗可降低肾脏损伤和细胞因子水平至正常氧水平。肾脏损伤的减轻伴随着氧化应激和 NF-B 表达的减少。因此，我们提出，抗 Tn 单克隆抗体治疗通过抑制新生小鼠的氧化应激和炎症来改善高氧诱导的肾损伤。
