摘要
目的 评价盐酸戊乙奎醚对大鼠内毒素性急性肺损伤时血管生成素-1（Ang-1）和酪氨酸激酶受体-2（Tie-2）水平的影响.方法 成年雄性SD大鼠40只,4～6月龄,体重180 ～ 220 g,采用随机数字表法,将其分为4组（n=10）：对照组（C组）、肺损伤组（ALI组）、盐酸戊乙奎醚低剂量组（L-PHC组）和盐酸戊乙奎醚高剂量组（H-PHC组）.ALI组尾静脉注射脂多糖（LPS）5.0 mg/kg,L-PHC组和H-PHC组于静脉注射LPS后1和24 h时分别尾静脉注射盐酸戊乙奎醚0.6、2.0 mg/kg.于首次注射盐酸戊乙奎醚后48 h时,处死大鼠,测定肺组织含水量、支气管肺泡灌洗液（BALF）蛋白浓度和肺组织Ang-1、Tie-2及磷酸化Tie-2的表达（Western blot法）,光镜下观察肺组织病理学结果,透射电镜下观察肺泡上皮屏障结构.结果 与C组比较,ALI组、L-PHC组和H-PHC组肺组织含水量、BALF蛋白浓度升高,肺组织Ang-1和磷酸化Tie-2表达下调（P＜0.05）；与ALI组比较,H-PHC组肺组织含水量、BALF蛋白浓度降低,肺组织Ang-1和磷酸化Tie-2表达上调（P＜0.05）,L-PHC组上述指标差异无统计学意义（P＞0.05）.H-PHC组肺组织损伤较ALI组减轻.结论 盐酸戊乙奎醚可改善肺血管环通透性,减轻肺泡上皮屏障损伤,从而减轻大鼠内毒素性急性肺损伤,且该作用与剂量有关,其机制与上调Ang-1表达和增强Tie-2活性有关.
Objective To evaluate the effect of penehyclidine hydrochloride （PHC） on the level of angiopoietin-1 （Ang-1） and tyrosine kinase receptor-2 （Tie-2） during endotoxin-induced acute lung injury （ALI） in rats.Methods Forty adult male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 4 groups using a random number table （n =10 each）：control group （group C）,ALI group,low-dose PHC group （group L-PHC） and high-dose PHC group （group H-PHC）.ALI was induced with iv injection of lipopolysaccharide 5.0 mg/kg via the tail vein.In L-PHC and H-PHC groups,PHC 0.6 and 2 mg/kg were injected,respectively,via the tail vein at 1 and 24 h after lipopolysaccharide injection.The rats were sacrificed at 48 h after the initial injection of PHC to measure the lung water content,protein concentration in bronchoalveolar lavage fluid （BALF）,and the expression of Ang-1,Tie-2 and phosphorylated Tie-2 in lung tissues.The morphological changes of lung tissues were observed under light microscope and the ultrastructural changes of alveolar epithelial barrier under transmission electron microscope.Results Compared with group C,the lung water content and protein concentrations in BALF were significantly increased,and the expression of Ang-1 and phosphorylated Tie-2 was down-regulated in the other three groups （P 〈 0.05）.Compared with group ALI,the lung water content and protein concentrations in BALF were significantly decreased,and the expression of Ang-1 and phosphorylated Tie-2 was up-regulated in H-PHC group （P 〈 0.05）,and no significant changes were found in the parameters mentioned above in group L-PHC （P 〉0.05）.The damage to lung tissues was significantly reduced in group H-PHC as compared with group ALI.Conclusion PHC can improve the permeability of pulmonary microvascular and reduce injury to alveolar epithelial barrier,thus ameliorating endotoxin-induced ALI in rats,and the effect is dose-related and up-regulation of Ang-1 expression and inhancement of Tie-2 activity are involved in the mechanism.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2013年第9期1138-1141,共4页
Chinese Journal of Anesthesiology
