盐酸戊乙奎醚对新生大鼠内毒素性急性肺损伤时肺氧化应激和细胞凋亡的影响

目的评价盐酸戊乙奎醚对新生大鼠内毒素性急性肺损伤(acute lung injury,ALI)时肺氧化应激和细胞凋亡的影响。方法清洁级健康雄性Wistar大鼠30只,7日龄,体重12~18g。采用随机数字表法分为三组:盐酸戊乙奎醚组(PHC组)、ALI组和生理盐水组(NS组),每组10只。PHC组和ALI组大鼠腹腔注射内毒素5.0mg/kg制备ALI模型。PHC组于内毒素注射前1h腹腔注射盐酸戊乙奎醚2.0mg/kg,NS组和ALI组给予等容量生理盐水。于注射内毒素4h后处死大鼠取肺组织标本,计算肺湿/干重比(W/D),采用硫代巴比妥酸法测定丙二醛(MDA)浓度,黄嘌呤氧化酶法测定大鼠超氧化物歧化酶(SOD)活性,免疫组织化学法测定细胞色素C(Cyt-C)、半胱氨酸天冬蛋白酶-3(Caspase-3)的含量,TUNEL法计数凋亡细胞,计算细胞凋亡指数(AI)。结果与NS组比较,ALI组和PHC组肺W/D和MDA浓度明显升高,SOD活性明显降低(P0.05);与ALI组比较,PHC组肺W/D和MDA浓度明显降低,SOD活性明显升高(P0.05)。与NS组比较,ALI组和PHC组Cyt-C、Caspase-3含量和AI明显升高;与ALI组比较,PHC组Cyt-C、Caspase-3含量和AI明显降低(P0.05)。结论盐酸戊乙奎醚可能通过抑制肺组织氧化应激和细胞凋亡,减轻新生大鼠内毒素性急性肺损伤。

Effects of penehyclidine hydrochloride on oxidative stress and cell apoptosis during endotoxin induced acute lung injury in neonatl rats

Objective To evaluate the effects of penehyclidine hydrochloride on the oxidative stress and cell apoptosis during endotoxin-induced acute lung injury (ALI) in neonatal rats. Methods Forty 7-day-old Wistar rats weighing 12-18 g were randomly divided into 3 groups (n=10 each) using a random number table: penehyclidine hydrochloride group (group PHC), acute lung injury (group AKI) and normal saline group (group NS). The ALI model was induced with intraperitoneal endotoxin 5.0 mg/kg in groups PHC and ALI. In group PHC, penehyclidine hydrochloride 2.0 mg/kg was injected intraperitoneally at 1 h before ALI respectively, while the equal volume of normal saline was administered in groups NS and ALI. At 4 h after endotoxin injection,the rsts were sacrificed. The lungs were collected to determine the wet/dry (W/D) lung weight ratio. The expression of SOD was detected by xanthine oxidase method. The expression of MDA was detected by sulfuretted barbitone method. Levels of cytochrome C (Cyt-C) and Caspase-3 were determined with immunohistochemical method (IHC), and cell apoptosis (by TUNEL). Apoptotic index was calculated. Results Compared with group NS, the W/D ratio and the contents of MDA were significantly increased, the contents of SOD were significantly decreased in groups ALI and PHC (P<0.05). Compared with group ALI, the W/D ratio and the contents of MDA were significantly decreased, the contents of SOD were significantly increased in group PHC (P<0.05). Compared with group NS, the contents of Cyt-C, Caspase-3, and apoptotic index were significantly increased in groups ALI and PHC (P<0.05). Compared with group ALI, the contents of Cyt-C, Caspase-3, and apoptotic index were significantly decreased in group PHC (P<0.05). Conclusion Penehyclidine hydrochloride ameliorates endotoxin-induced ALI by inhibiting oxidative stress and cell apoptosis in neonatal rats.