文章摘要
盐酸戊乙奎醚在大鼠急性重症胰腺炎相关肺损伤中的作用
Effects of penehychdine hydrochloride on severe acute pancreatitis associated acute lung injury in rats
  
DOI：
中文关键词: 盐酸戊乙奎醚  重症急性胰腺炎  急性肺损伤  缺氧诱导因子-1α
英文关键词: Penehychdine hydrochloride  Severe acute pancreatitis  Acute lung injury  Hypoxia inducible factor-1α
基金项目:国家自然科学基金（81301618）
作者单位E-mail
邱丽丽 450047,郑州颐和医院麻醉科  
邓芳 郑州颐和医院麻醉科  
朱荣涛 郑州大学第一附属医院肝胆胰外科 zrt0371@163.com 
张言鹏 郑州大学第一附属医院肝胆胰外科  
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中文摘要:
      
目的 探讨盐酸戊乙奎醚在大鼠急性重症胰腺炎相关肺损伤(PALI)中的作用及对缺氧诱导因子(HIF)-1α相关炎症因子表达的影响。
方法 40只健康雄性成年SD大鼠，应用随机数字法分为三组：假手术组(S组，n=8)、PALI模型组(ALI组，n=16)、盐酸戊乙奎醚+PALI模型组 (P组，n=16)。ALI组和P组采用4％牛磺胆酸钠 1 ml/kg 逆行性胰胆管注射法建立大鼠PALI模型。P组在建立模型后即刻给予大鼠腹腔内注射盐酸戊乙奎醚，S组和ALI组经腹腔注射等量生理盐水。造模后12 h处死大鼠，取肺组织称重后计算肺湿干重比(W/D)，光镜下观察胰腺及肺组织病理学评分，ELISA法测定肺组织HIF-1α、IL-1β、IL-6蛋白含量和血清胰淀粉酶含量，Western blot检测肺组织TLR4、NF-κB p65蛋白含量。
结果 ALI组和P组大鼠的胰腺组织均存在广泛的中性粒细胞浸润、腺泡出血坏死和脂肪坏死。与S组比较，ALI组与P组胰腺病理评分、肺损伤评分、肺W/D明显升高，胰淀粉酶含量明显降低(P<0.01)；与ALI组比较，P组肺损伤评分、肺W/D明显降低(P<005)。与S组比较，ALI组和P组大鼠肺组织HIF-1α、IL-1β、IL-6含量明显升高，肺组织TLR4、NF-κBp65含量明显升高(P<0.01)；与ALI组比较，P组肺组织HIF-1α、IL-1β、IL-6含量明显降低，TLR4、NF-κB p65蛋白含量明显降低(P<0.05)。
结论 盐酸戊乙奎醚在不改变急性重症胰腺炎的胰腺组织损伤的情况下能够显著减轻急性重症胰腺炎相关肺损伤，机制可能与抑制HIF-1α等相关炎性因子的表达相关。
英文摘要:
      
Objective To investigate the effect of penehychdine hydrochloride (PHCD) on acute lung injury induced by acute severe acute pancreatitis and the expression of hypoxia inducible factor-1α (HIF-1α) in rats.
Methods Forty healthy adult male SD rats were used and randomly divided into 3 groups, group S of sham operation, group ALI of pancreatitis-associated acute lung injury (PALI) and group P of PALI with PHCD. Rats of group ALI and group P were the model established of acute lung injury associated with SAP by retrograde injection of 4％ sodium taurocholate into biliopancreatic duct. Rats of group P of acute lung injury with SAP were immediately given PHCD after SAP. Rats of group S and group ALI were injected the same amount of 0.9% sodium chloride solution. After modeling, the rats were sacrificed at 12h. The wet/dry weight ratio (W/D) of lung tissue was calculated. Pathological changes of pancreatic and lung tissues were scored. HIF-1α,IL-1β,IL-6 of lung tissues and serum amylase were detected by ELISA. The expression of TLR4, NF-κB p65 in lung tissue was detected by Western blot.
Results Extensive infiltration of neutrophils, alveolar hemorrhage and necrosis and fat necrosis with pancreatic tissue were observed in group PALI and group P. Pancreatic tissue injury score was significantly higher than that of group S (P<0.01). However, there was no statistically significant difference between the level of serum amylase in group P and group ALI. The W/D ratio of lung tissue in rats of group ALI and group P was significantly higher than those in group S (P<0.05). Compared with those of group ALI, the lung tissue pathological changes of group P were significantly improved, and the lung W/D value was significantly lower than that of group ALI (P<0.05). Compared with group S, the expression of TLR4, NF-κB p65, HIF-1α in lung tissue of group ALI and group P was significantly higher (P<0.01), and the expression of TLR4, NF-κB p65, HIF-1α, IL-1β and IL-6 in group P was significantly lower than that in group ALI (P<0.05).
Conclusion PHCD could not alleviate the damage of pancreatic tissue of SAP. It suppressed the expression of HIF-1α, IL-1β and IL-6 and reduced the acute lung injury induced by SAP in rats, which might be depended on suppressing the expression of inflammatory factors, such as HIF-1α.
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