摘要
目的探讨阿米洛利预先给药对大鼠内毒素性急性肺损伤的影响.方法清洁级雄性SD大鼠32只,体重200~250 g,随机分为4组(n=8):对照组(C组)、急性肺损伤组(ALI组)、阿米洛利组(A组)和阿米洛利预先给药组(AL组).C组股静脉输注生理盐水3 ml,ALI组股静脉输注生理盐水1 ml、内毒素6 mg/kg,A组股静脉输注阿米洛利10 mg/kg、生理盐水2 ml,AL组股静脉输注阿米洛利10 mg/kg、内毒素6 mg/kg,输注速率均为0.05 ml/rain,给药间隔均为30 min.于输注内毒素结束后6 h时处死大鼠取肺,观察肺组织病理学,并行病理学评分,称重后计算肺湿干重比,检测髓过氧化物酶(MPO)活性,测定支气管肺泡灌洗液总蛋白、TNF-α和巨噬细胞炎性蛋白-2(MIP-2)的浓度,采用Western blot法检测肺组织钠氢交换体1(NHE1)、p38丝裂原活化蛋白激酶(p38MAPK)和细胞外信号调节激酶(ERK)的表达水平.结果与C组比较,ALI组和AL组肺组织病理学评分、肺湿干重比、MPO活性、支气管肺泡灌洗液总蛋白、TNF-α和MIP-2浓度、肺组织NHE1、p38MAPK和ERK的表达水平明显升高(P<0.01),A组上述指标差异无统计学意义(P>0.05);与ALI组比较,AL组肺组织病理学评分、肺湿干重比、MPO活性、支气管肺泡灌洗液总蛋白、TNF-α和MIP-2浓度、肺组织NHE1和ERK的表达水平明显降低(P<0.01),p38MAPK表达差异无统计学意义(P>0.05).结论阿米洛利预先给药可减轻大鼠内毒素性急性肺损伤,其机制可能与抑制ERK信号转导通路激活有关.
Objective To investigate the effect of amiloride pretreatment on the acute lung injury(ALI)induced by lipopolysaccharide(LPS)in rats.Methods Thirty-two pathogen-free male SD rats weighing 200-250 g were randomly divided into 4 groups(n=8 each);groupⅠreceived iv normal saline(group C);groupⅡALI received iv LPS 6 mg/kg(group ALI);groupⅢreceived iv amiloride 10 mg/kg(group A)and groupⅣreceived amiloride 10 mg/kg iv 30 min before iv LPS(group AL).The animals were killed by exsanguination at 6 h after iv LPS infusion.The lungs were immediately removed.Microscopic examination of lung tissue was performed.The left lung was lavaged.The total protein(TP),TNF-αand macrophage inflammatory protein-2(MIP-2)concentrations in broncho-alveolar lavage fluid(BALF)were measured.The W/D weight ratio and the myeloperoxidase(MPO)activity and expression of Na-H exchanger-1(NHE1),p38MAPK and extracellular signal-regulated kinase(ERK)in lung tissue were determined.Results LPS significantly increased ALI score(0=slightest,4=severest),W/D lung weight ratio,TP,TNF-αand MIP-2 concentrations in BALF and MPO activity and the expression of NHE1,p38MAPK and ERK in the lung as compared with.control group.Amiloride pretreatment significantly attenuated LPS-induced changes except p38MAPK expression.Conclusion Pretreatment with amiloride can attenuate LPS-induced ALI by inhibition of ERK activation.
作者
朱宏飞
桂平
姚尚龙
武庆平
冯丹
程瑾
ZHU Hong-fei;GUI Ping;YAO Shang-long;WU Qing-ping;FENG Dan;CHENG Jin(Department ofAnesthesiology,Union Hospital,Tongfi Medical College,Huazhong University ofScience and Technology,Wuhan 430022,China)
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2010年第5期601-604,共4页
Chinese Journal of Anesthesiology
基金
国家自然科学基金(30571787,30930089)
贝朗麻醉科学研究基金
