CAJ | 학술논문

目的：检测普罗布考（probucol，PRO）对心衰大鼠心肌中基质金属蛋白酶-3（MMP-3）、基质金属蛋白酶抑制剂-3（TIMP-3）及骨桥蛋白（osteopontin，OPN）表达的影响，探讨PRO对心衰的干预作用。方法采用阿霉素（adriamycin）诱导大鼠心衰模型，120只雄性Wistar大鼠，15只为对照组，105只诱导心衰后分成2组：普罗布考治疗组（ PRO组）、心衰组（ ADR组）。将PRO组给予普罗布考500 mg· kg－1· d－1蒸馏水配液灌胃，对照组、ADR组给予同等剂量蒸馏水灌胃，连续干预4周。行心脏超声、心肌组织病理及超微结构检测，免疫组化法测OPN、MMP-3、TIMP-3。结果①心衰组较对照组左室射血分数（ EF ）、左室短轴缩短率（FS）均减低（P＜0.01），鼠体重、全心重／体重、左室重量变化显著（P＜0.05，P＜0.05， P＜0.01）；OPN、MMP-3表达升高，TIMP-3降低，差异具有统计学意义（P＜0.05）。②PRO组较ADR组大鼠EF、FS明显提高（分别P＜0.05，P＜0.01），MMP-3、OPN表达降低，TIMP-3表达升高，差异均有统计学意义（ P＜0.05）。③PRO组与对照组均无显著差异。结论普罗布考可降低大鼠心衰时心肌细胞外基质OPN和MMP-3的合成，促进TIMP-3的表达，有逆转心肌重构，改善心功能作用。
목적：검측보라포고（probucol，PRO）대심쇠대서심기중기질금속단백매-3（MMP-3）、기질금속단백매억제제-3（TIMP-3）급골교단백（osteopontin，OPN）표체적영향，탐토PRO대심쇠적간예작용。방법채용아매소（adriamycin）유도대서심쇠모형，120지웅성Wistar대서，15지위대조조，105지유도심쇠후분성2조：보라포고치료조（ PRO조）、심쇠조（ ADR조）。장PRO조급여보라포고500 mg· kg－1· d－1증류수배액관위，대조조、ADR조급여동등제량증류수관위，련속간예4주。행심장초성、심기조직병리급초미결구검측，면역조화법측OPN、MMP-3、TIMP-3。결과①심쇠조교대조조좌실사혈분수（ EF ）、좌실단축축단솔（FS）균감저（P＜0.01），서체중、전심중／체중、좌실중량변화현저（P＜0.05，P＜0.05， P＜0.01）；OPN、MMP-3표체승고，TIMP-3강저，차이구유통계학의의（P＜0.05）。②PRO조교ADR조대서EF、FS명현제고（분별P＜0.05，P＜0.01），MMP-3、OPN표체강저，TIMP-3표체승고，차이균유통계학의의（ P＜0.05）。③PRO조여대조조균무현저차이。결론보라포고가강저대서심쇠시심기세포외기질OPN화MMP-3적합성，촉진TIMP-3적표체，유역전심기중구，개선심공능작용。
Objective To detect the influence of probucol ( PRO) on the expressions of matrix metalloproteinases-3 ( MMP-3 ) , matrix metalloproteinases inhibitor-3 ( TIMP-3 ) , and os-teopontin ( OPN) in myocardium of rat with heart failure and the interventional effect of PRO on cardiac failure .Methods Rat model of heart failure was induced by adriamycin among 120 male Wistar rats , 15 rats for control group , and 105 rats were divided into 2 groups after in-duced heart failure:probucol group ( PRO) and heart failure group ( ADR) .PRO group were received probucol 500 mg · kg -1 · d-1 and distilled water with liquid gavage , while control group and ADR group were given the same dose of distilled water , with continuous intervention for 4 weeks .Echocardiography , myocardial histopathology and ultrastructure detection were performed, OPN, MMP-3, TIMP-3 were detected by immunohistochemical method .Results①In ADR group, left ventricular ejection fraction (EF), left ventricular fractional shortening ( FS) were lower compared with control group ( P<0.01 ) , the weight of the rat , whole heart heavy weight/body weight , left ventricular weight changed significantly ( P<0.05 , P<0.05 , P<0.01 );OPN, MMP-3 expression was increased , TIMP-3 was lower , the differences were statistically significant (P<0.05).②In PRO group, EF, FS increased significantly compared with ADR group ( P<0.05 , P<0.01 ) , MMP-3 , OPN expression was decreased , TIMP-3 ex-pression was increased , the differences were statistically significant ( P<0.05 );③There was no significant difference between PRO group and control group .Conclusion Probucol can re-duce synthesis of myocardial extracellular matrix OPN , MMP-3 and elevated TIMP-3 , and re-versing myocardial remodeling and improving cardiac function .