富马酸氯马斯汀对大鼠高原缺氧肺损伤的影响

Effects of clemastine fumarate on hypoxic lung injury in rats at high altitude

目的探讨富马酸氯马斯汀(clemastine fumarate,CLE)对大鼠高原缺氧肺损伤的影响。方法按照随机数字表法,将40只8周龄雄性SD大鼠分为对照组(C组)、高原缺氧肺损伤组(HH组)、地塞米松治疗组(DXM组)、氯马斯汀治疗组(CLE组),每组10只。将HH组、DXM组和CLE组以低压低氧模式放入动物实验舱,DXM组入舱前1 h开始每6 h肌注2 mg/kg DXM,CLE组入舱前2 h按0.9 mg/kg肌注CLE,入舱10 h后按0.9 mg/kg追加一次用药,完成造模。立即处死大鼠,测肺组织湿/干重比(W/D);HE染色观察肺组织病理学变化;PCR检测肺组织中白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)、Toll样受体4(TLR4)和核因子κB(NF-κB)的mRNA水平;Western blot法检测IL-1β、TNF-α、TLR4和NF-κB蛋白表达水平。结果与C组比较,HH组、DXM组、CLE组肺组织W/D比值明显升高(P<0.05),肺组织中IL-1β、TNF-α、TLR4、NF-κB的mRNA转录水平和蛋白表达水平均明显升高(P<0.05)。与HH组比较,DXM组和CLE组肺组织W/D比值明显降低(P<0.05),肺组织中IL-1β、TNF-α、TLR4、NF-κB的mRNA转录水平和蛋白表达水平均明显降低(P<0.05)。结论富马酸氯马斯汀可以减轻大鼠高原缺氧肺损伤程度。

Objective To explore the effect of clemastine fumarate on hypoxic lung injury in rats at high altitude.Methods Forty eight-week-old male SD rats were equally divided into the control group(group C),high altitude hypoxia lung injury group(HH group),dexamethasone treatment group(DXM group)and clemastine fumarate treatment group(CLE group)using the random number table method.The HH group,DXM group and CLE group were put into an animal experiment cabin separately in a low-pressure and hypoxic mode.The DXM group was intramuscularly injected with 2 mg/kg DXM every 6 hours starting from one hour before entry.The CLE group was intramuscularly injected with 0.9 mg/kg 2 h before entry,and another dose of 0.9 mg/kg was given 10 hours after entry into the cabin,thus completing the establishment of the model.The rats in each group were immediately sacrificed before the wet/dry weight ratio(W/D)of the upper lobes of right lungs was measured.HE staining was performed on the tissues of the lower lobes of right lungs.The mRNA levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),toll-like receptor 4(TLR4)and nuclear factorκB(NF-κB)in lung tissues were detected by PCR.Expression levels of IL-1β,TNF-α,TLR4 and NF-κB were determined by Western blot.Results Compared with the control group,the W/D ratios of the HH group,DXM group and CLE group were significantly increased(P<0.05),so were the mRNA transcription and protein expression levels of IL-1β,TNF-α,TLR4 and NF-κB in lung tissues(all P<0.05).Compared with the HH group,the W/D ratios of DXM group and CLE group were significantly decreased(P<0.05),so were mRNA transcription and protein expression levels of IL-1β,TNF-α,TLR4 and NF-κB(all P<0.05).Conclusions Clemastine fumarate can reduce the degree of high altitude hypoxic lung injury in rats.