ABSTRACT
Objective To evaluate the effect of penehyclidine hydrochloride on hyperoxia-induced acute lung injury and the relationship with endoplasmic reticulum stress-dependent apoptosis in infantile rats.Methods Ninety-six clean-grade male infantile Sprague-Dawley rats,weighing 40-50 g,aged 14 days,were allocated into 4 groups (n =24 each) using a random number table method:control group (C group),penehyclidine hydrochloride group (P group),hyperoxia group (HO group) and hyperoxia plus penehyclidine hydrochloride group (HP group).Infantile rats were intravenously injected with penehyclidine hydrochloride (0.3 mg/kg) at the same time point every day for 3 consecutive days in P and HP groups.Infantile rats were injected with the equal volume of normal saline instead of penehyclidine hydrochloride in C and H groups.Acute lung injury was induced by inhaling oxygen at concentration greater than 90％ for 72 h starting from 4th day after administration.Infantile rats were sacrificed at the end of inhaling,and lungs were removed for examination of the pathological changes and for determination of weight to dry weight ratio (W/D ratio),index of quantitative evaluation for alveolar damage (IQA),pneumonocyte apoptosis (using TUNEL),expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) protein and mRNA in lung tissues (by Western blot or using reverse transcription-polymerase chain reaction).The mitochondrial injury score was assessed,and apoptotic index (AI) was determined.Results Compared with C group,the W/D ratio,IQA,AI and mitochondrial injury score were significantly increased,and the expression of GRP78 and CHOP protein and mRNA was up-regulated in HO and HP groups (P＜0.05),and no significant change was found in the parameters mentioned above in group P (P＞0.05).Compared with HO group,the W/D ratio,IQA,AI and mitochondrial injury score were significantly decreased,the expression of GRP78 and CHOP protein and mRNA was downregulated (P ＜ 0.05),and the pathological changes of lung tissues were significantly attenuated in HP group.Conclusion Penehyclidine hydrochloride can mitigate hyperoxia-induced acute lung injury,and the mechanism may be related to inhibiting endoplasmic reticulum stress-dependent apoptosis in infantile rats.