摘要
目的:研究盐酸多西环素对内毒素诱导大鼠急性肺损伤(ALI)的保护作用.方法:将72只雄性SD大鼠随机分为对照组,损伤组(ALI组),脂多糖治疗组(LPS组),每组24只.每组按造模后不同观察时间点又分为1,2,4,8h4个亚组(n=6).于0h时给予对照组气管内滴注生理盐水(NS)0.3mL,10min后股静脉注射NS1mL.ALI组气管内滴注LPS0.2mg/kg(溶于0.3mLNS),10min后股静脉注射NS1mL.LPS组气管内滴注LPS0.2mg/kg,10min后股静脉注射盐酸多西环素20mg/kg(溶于1mLNS).各组于1,2,4,8h4个时间点心脏抽血检测动脉血氧分压(PaO2);取肺组织进行肺湿/干质量(W/D)比值测定,并采用HE染色观察肺组织形态学变化;免疫组织化学法检测肺组织中基质金属蛋白酶-2(MMP-2),基质金属蛋白酶-9(MMP-9)表达.结果:给予气管内滴注LPS后1～8h大鼠动脉血PaO2ALI组,LPS组显著降低,4h时达最低点,各时间点动脉血PaO2LPS组均显著高于ALI组(P<0.05,P<0.01).W/D比值1～8h时ALI组,LPS组均显著增加,2组相比较LPS组较ALI组降低(P<0.05,P<0.01).病理形态学观察可见LPS组肺水肿、出血、炎性细胞浸润程度程度较ALI组减轻.免疫组化结果显示ALI组肺组织MMP-2,MMP-9在气管内滴入LPS后1h后迅速升高,4h时达峰值,LPS组MMP-2,MMP-9表达在相同时间均较ALI组显著降低(P<0.05,P<0.01).而对照组肺组织MMP-2,MMP-9在不同时间点无明显变化.结论:盐酸多西环素可抑制内毒素性大鼠ALI肺组织MMP-2,MMP-9表达,改善呼吸氧合功能,减轻肺损伤.
AIM： To explore the mechanism of doxycycline in the treatment of endotoxin-indnced acute lung injury （ALl） in rats. METHODS： Seventy-two male SD rats were randomly divided into 3 groups ： control group （ n = 24 ）, ALI group （ n = 24 ） and treatment group（n =24）. The rats in the ALl group were treated with lipopolysaccharide（LPS） by intratracheal injection to induce acute lung injury, followed by injection of 1 mL normal saline, the rats in the treatment group were first treated with LPS and then with Doxycycline 20 mg/kg（ dissolved in 1 mL NS）and the rats in the control group were treated with normal saline. The animals in the 3 groups were killed 1,2, 4 and 8 h after operation and then blood gas was monitored and the lung tissue wet/dry weight（ W/ D） was detected. The histopathology of the lung injury was observed by light microscope, and the expressions of matrix metalloproteinase-2 （ MMP-2 ） and matrix metalloproteinase-9 （ MMP-9 ） proteins in the lung tissues were detected by immunohistochemistry. RESULTS ： Arterial partial pressure of oxygen （ PaO2 ） in the ALl group and the treatment group decreased rapidly after the rats were treated with LPS by intratraeheal injection. PaO2 in the ALl group was lower than that in the treatment group（P 〈0.05, P 〈0.01 ）. The W/D value of the ALI and the treatment group was significantly higher（P 〈 0. 05）, and the W/D value of the treatment group was lower than that of the ALI group, with statistical difference （ P 〈 0.05 ,P 〈0.01 ）. The degree of lung injury, including lung swelling, neutrophil cells infiltration and hemorrhage, in the treatment groups was milder. The expressions of MMP-2 and MMP-9 in lung tissues in the ALl group rapidly increased after intratracheal injection and reached peak at 4 h. The expressions of MMP-2 and MMP-9 in the ALI group were higher than those in the treatment group at all time points （ P 〈 0.05, P 〈 0.01 ）. No significant changes were observed in the control group
出处
《第四军医大学学报》
北大核心
2009年第17期1560-1563,共4页
Journal of the Fourth Military Medical University
基金
西安市科技发展引导项目[SF09026(2)]
