肺泡灌洗液计数中性粒细胞百分比与血浆MMP-9、 TIMP-1在油酸制备急性肺损伤大鼠模型中的相关性研究

目的检测油酸制备大鼠急性肺损伤模型支气管肺泡灌洗液（bronchoalveolarlavagefluid，BALF）计数中性粒细胞（polymorphonucearleukocyte，PMN）百分比及血浆基质金属蛋白酶9（matrixmetalloproteinases9，MMP-9）、组织基质金属蛋白酶抑制因子-1（tissuematrixmetalloproteinaseinhibitor-1，TIMP-1）含量，分析BALF中性粒细胞百分比与MMP-9及TIMP-1的相关性及临床意义。方法雄性SD大鼠36只随机分为3组：空白对照组（n=12）、油酸造模2h组（n=12）、油酸造模6h组（n=12）。空白对照组大鼠尾静脉注射生理盐水（0．1ml／kg）6h后观察。油酸造模组大鼠尾静脉缓慢注射油酸（OA，0．1ml／kg）2、6h后观察，以复制油酸诱导大鼠急性肺损伤模型。观察及检测指标为光镜下肺组织病理形态学变化、动脉血氧分压（PaO，）、肺湿／干重比（W／D）、血浆MMP-9和TIMP-1含量及肺泡灌洗液中性粒细胞计数百分比。结果光镜下，与空白对照组比较，油酸造模组大鼠肺组织可见明显形态学改变。2h及6h油酸造模组PMN％明显升高，PaO，明显降低，IQA及W／D明显升高，（P均〈0．01）；血浆MMP-9含量明显升高（P〈0．001），血浆TIMP-1含量明显降低（P〈0．05）血浆MMP-9含量与PMN％均呈高度正相关，血浆TIMP-1含量与PMN％均呈高度负相关。结论油酸制备急性肺损伤大鼠模型肺泡灌洗液PMN％明显升高，血浆MMP-9含量明显升高，TIMP-1含量明显降低。血浆MMP-9、TIMP—l与肺泡灌洗液PMN％呈高度相关性；检测血浆MMP-9、TIMP-1有助于急性肺损伤的病理诊断和治疗，从而为临床急性肺损伤的诊断、治疗及预后提供更为简单、可行、准确的检测方法和途径。

Correlation between BALF and MMP -9 and TIMP -1 in Acute Lung Injury Model of Rat Induced by Oleic Acid.

Objective To detect the percentage of polymorphonucear leukocyte（PMN% ） in bronchoalveolar lavage fluid（BALF） and the levels of matrix metalloproteinases 9 （MMP- 9 ） and tissue matrix metalloproteinase inhibitor- 1 （ TIMP- 1 ） in plasma of acute lung injury model of rats induced by oleic acid to analyze the clinical meaning and Correlation between BALF and MMP -9 ,TIMP - 1. Methods 36 male SD rats were randomly divided into three groups： normal control group （n = 12） , oleie acid model control group for 2h （n = 12） and oleic acid model control group for 6h （n = 12）. With the slow tail vein injection of oleic acid （OA, 0.1 ml/kg） of rats in oleic acid model control group, rats in normal control group were injected with sodium chloride （0.1 ml/kg）. The observation and measurement indi-cators were the pathological changes of lung in light microscope, arterial partial pressure of oxygen （ PaO2 ）, lung wet / dry weight ratio （W/D）, the levels of MMP -9 and TIMP - 1 in plasma,PMN % in BALF. Results Histomorphology of lung： Compared with normal control group, in light microscope, pathological changes of histological lung in oleic acid model control group were significant which could see pulmonary interstitial and alveolar edema, a large amount of serous exudation, inflammatory cells, red blood cell leakage in alveolar cavity ; Part of the pulmonary interstitial thickening were uniformly stained ＂transparent membrane ＂pattern. Compared with normal control group, as 2h and 6h, PaO2 of rats in oleic acid model group decreased significantly （P 〈 0. O1 ） while W/D,IQA,, PMN% increased sig- nificantly （ P 〈 0. O1 ）. Compared with normal control group, as 2h and 6h, the level of MMP - 9 in plasma increased significantly （ P 〈 O. 001 ）. A high positive correlation was found between MMP - 9 in plasma and PMN% （ r = O. 7999,0. 7355, P 〈 O. 05 ）. Compared with normal control group, as 2h and 6h, the level of TIMP - 1 in plasma decreased significantly（P 〈0.05）. A high negative correlation was found between TIMP - 1 in plasma and PMN% （r = - 0. 8022, - 0. 7889,P 〈 0.05 ）. Cortelusiou PMN% in BALF increased signifi- cantly. The level of MMP - 9 in plasma increased significantly while that of TIMP - 1 decreased significantly of rats in oleic acid model control group. A high positive correlation was found between MMP-9 in plasma and PMN% ,while a high negative correlation was found between TIMP - 1 in plasma and PMN%. It suggestes the detection of plasma MMP - 9 and TIMP - 1 can contribute to the pathological di- agnosis and treatment of ALI, and then provide a simple, practical, accurate method for clinical diagnosis, treatment and prognosis of ALI.