CAJ | 학술논문

目的研究外源性基质金属蛋白酶-9(MMP-9)抑制剂巴马司他在心肺转流急性肺损伤中的保护作用.方法 30只健康杂种幼犬随机分为对照组、低剂量组和高剂量组.低剂量组术前连续3 d每天腹腔注射巴马司他10 mg/ks,高剂量组术前连续3 d每天腹腔注射巴马司他30 mg/kg.分别计算术前和术后肺泡-动脉氧分压差(A-aDO_2)和呼吸指数(RI).从手术前开始计时,分别于0、60、120和270 min时采集静脉血样,酶联免疫吸附法测血浆MMP-9浓度,RT-PCR法测定血MMP-9 mRNA表达变化.比色法测定支气管肺泡灌洗液(BALF)髓过氧化物酶活性,明胶酶谱法测定BALF MMP-9活性.计算肺湿/干质量比.光镜和电镜下观察肺组织形态学改变.结果 270 min时高剂量组血浆MMP-9浓度(17.36±1.18)μg/L,低于对照组的(30.47±2.22)μg/L(P<0.05).高剂量组术后A-aDO_2和RI较对照组明显改善(P<0.05),高剂量组肺湿/干质量比(2.8±0.5)较对照组(4.7 ±0.6)明显减低(P<0.05),且肺组织的病理改变显著减轻;但三组间血MMP-9 mRNA表达无明显差异(P>0.05).结论巴马司他通过降低MMP-9的浓度及活性,减轻细胞基底膜的降解,减轻肺泡白细胞浸润和肺水肿,起到肺保护的作用.
목적 연구외원성기질금속단백매-9(MMP-9)억제제파마사타재심폐전류급성폐손상중적보호작용.방법 30지건강잡충유견수궤분위대조조、저제량조화고제량조.저제량조술전 련속3 d매천복강주사파마사타10 mg/ks,고제량조술전련속3 d매천복강주사파마사타30 mg/kg.분별계산술전화술후폐포-동맥양분압차(A-aDO_2)화호흡지수(RI).종수술전개시계시,분별우0、60、120화270 min시채집정맥혈양,매련면역흡부법측혈장MMP-9농도,RT-PCR법측정혈MMP-9 mRNA표체변화.비색법측정지기관폐포관세액(BALF)수과양화물매활성,명효매보법측정BALF MMP-9활성.계산폐습/간질량비.광경화전경하관찰폐조직형태학개변.결과 270 min시고제 량조혈장MMP-9농도(17.36±1.18)μg/L,저우대조조적(30.47±2.22)μg/L(P<0.05).고제량조 술후A-aDO_2화RI교대조조명현개선(P<0.05),고제량조폐습/간질량비(2.8±0.5)교대조조(4.7 ±0.6)명현감저(P<0.05),차폐조직적병리개변현저감경;단삼조간혈MMP-9 mRNA표체무명현차이(P>0.05).결론 파마사타통과강저MMP-9적농도급활성,감경세포기저막적강해,감경폐 포백세포침윤화폐수종,기도폐보호적작용.
Objective To investigate the protective effect of exogenous inhibitor of matrix metallopmteinases-9(MMP-9),batimastat,in the lung injury induced by cardiopulmonary bypass(CPB)in dogs.Methods Thirty healthy mongrel puppies were randomly divided into 3 groups:control group,lowdose group [batimastat 10 mg/(kg-d) for 3 days before operation]and high-dose group[batirnastat 30 established.and hemodynamic and respiratory parameters were monitored.The preoperative and postoperative alveolar-arterial oxygen difference(A-aDO_2)and respiratory index (RI) were calculated.From the beginning of surgery,blood samples were taken at the time 0,60,120,and 270 min Plasma concentrations of MMP-9 were measured by ELISA,and blood MMP-9 mRNA expressions were deterrnined bv RT-PCR The myelopemxidase (MPO) activity of centrifugal bronchoalveolar lavage fluid were measured by Colorimetry.And MMP-9 activity was determined by Gelatin zymography.Light and electronic microscope were used to observe the morphological changes of lung tissue.A small piece of left lung tissue wag taken.weighed and baked to calculate the wet weiight(W/D)index.Results After cardiopulmonary bypass,the concentrations of MMP-9 and mRNA expressions of the control group were increased significantly.and lung injury was apparent.At 270 min,the MMP-9 plasma concentration of high-dose group(17.36±1.18)μLwas significant reducing than control group(30.47±2.22)μg/L(P<0.05),After operation,A-aDO_2 and RI of hiSh-dose group were significantly impmved than control group(P<0.05).,The W/D index of the high-dose group(2.8±0.48) was significantly lower than that of control group (4.7±0.6)(P<0.05). And the pathological changes of lung tissue were significantly improved in the high-dose group.However.there Was no significant difference in the MMP-9 mRNA expression in three groups.Conclusions Batimastat plays a role in the protection of the lung injury of CBP by reducing the concentration and activity of MMP-9, the degradation of the cell membrane and pulmonary neutrophil infiltration and reduction of pulmonary edema.