Department of Anatomy and Cellular Biology, School of Medicine, College of Medicine, Taipei Medical University , Taipei , Taiwan.
Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University , Taipei , Taiwan.
Ren Fail. 2019 Nov;41(1):733-741. doi: 10.1080/0886022X.2019.1651741.
Supplemental oxygen is often used to treat neonates with respiratory disorders. Human and animal studies have demonstrated that neonatal hyperoxia increases oxidative stress and induces damage and collagen deposition in kidney during the perinatal period. Cathelicidin LL-37 is one important group of human antimicrobial peptides which exhibits antioxidant activity and its overexpression resists hyperoxia-induced oxidative stress. This study was designed to evaluate the protective effects of cathelicidin in hyperoxia-induced kidney injury in newborn rats. Sprague-Dawley rat pups were reared in either room air (RA) or hyperoxia (85% O) and were randomly treated with low-dose (4 mg/kg) and high-dose (8 mg/kg) cathelicidin in normal saline (NS) administered intraperitoneally on postnatal days 1-6. The following six groups were obtained: RA + NS, RA + low-dose cathelicidin, RA + high-dose cathelicidin, O + NS, O + low-dose cathelicidin, and O + high-dose cathelicidin. Kidneys were taken for Western blot and histological analyses on postnatal day 7. The hyperoxia-reared rats exhibited significantly lower body weights and anti-inflammatory M2 macrophages, but the kidney injury scores, oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells, pro-inflammatory M1 macrophages, collagen deposition, and NF-κB expression were higher than did the RA-reared rats. Cathelicidin treatment attenuated kidney injury as evidenced by lower kidney injury scores, 8-OHdG-positive cells, collagen deposition, and reversion of hyperoxia-induced M1/M2 macrophage polarization. The role of Cathelicidin in ameliorates kidney injury of the hyperoxia newborn rats was accompanied by decreased NF-κB expression, which probably through the modulating NF-κB activity in the kidney.
常给有呼吸障碍的新生儿补充氧气。人体和动物研究表明，新生儿高氧血症会增加氧化应激，并在围产期导致肾脏损伤和胶原沉积。Cathelicidin LL-37 是人类抗菌肽的一个重要家族，具有抗氧化活性，其过表达可抵抗高氧诱导的氧化应激。本研究旨在评估 Cathelicidin 在新生大鼠高氧诱导肾损伤中的保护作用。Sprague-Dawley 新生大鼠在空气（RA）或高氧（85% O ）中饲养，并随机接受低剂量（4mg/kg）和高剂量（8mg/kg）Cathelicidin 在正常盐水中（NS）腹腔内给药，于生后第 1-6 天。共获得以下 6 组：RA+NS、RA+低剂量 Cathelicidin、RA+高剂量 Cathelicidin、O+NS、O+低剂量 Cathelicidin 和 O+高剂量 Cathelicidin。于生后第 7 天取肾脏进行 Western blot 和组织学分析。高氧饲养的大鼠体重明显下降，抗炎 M2 巨噬细胞减少，但肾脏损伤评分、氧化应激标志物 8-羟基-2'-脱氧鸟苷（8-OHdG）阳性细胞、促炎 M1 巨噬细胞、胶原沉积和 NF-κB 表达均高于 RA 饲养的大鼠。Cathelicidin 治疗可减轻肾脏损伤，表现为肾脏损伤评分、8-OHdG 阳性细胞、胶原沉积降低，以及高氧诱导的 M1/M2 巨噬细胞极化逆转。Cathelicidin 在改善高氧新生大鼠肾脏损伤中的作用伴随着 NF-κB 表达的降低，这可能是通过调节肾脏中 NF-κB 的活性。
