同型半胱氨酸在酒精性心肌病发病中的作用

Role of homocysteine in the pathogenesis of alcoholic cardiomyopathy

目的 探讨同型半胱氨酸（Hcy）在酒精性心肌病（ACM）发病中的作用。方法 Wistar大鼠分为两组，酒精组（41只）和对照组（28只）。酒精组通过随意饮用白酒及定量灌胃6个月建立ACM模型。对照组以水代洒。动态榆测各组大鼠心脏功能、测定血浆Hcy水平、光镜观察心室肌组织病理改变、免疫组化法检测心肌组织基质金属蛋白酶9（MMP－9）表达以及Masson染色观察心肌纤维化程度。结果大量饮酒4个月时，酒精组较对照组左室舒张末期内径增大（7．0mm±0．6mm比5．0mm±0．4mm，P〈0．05），左室射血分数（52％±8％比78％±4％，P〈0．05）和左室短轴缩短率降低（31％±3％比47％±2％，P〈0．05），6个月时上述指标改变更明显（P〈0．01）；酒精组血浆Hcy水平自2个月起明显升高[（18．1-4-3．1）μmo]／I．比（9．8±2．1）μmol／L，P〈0．01]，4个月[（26．3±4．0）txmol／L，P〈0．05]、6个月更高[（30．9±3．6）μmol／L，P〈0．05]。4、6个月酒精组MMP-9表达高于实验前（0．161％±O．019％、0．263％±0．014％比0．050％±O．008％，P〈0．01），4、6个月酒精组Masson染色分析显示心肌胶原纤维高于实验前（10．23％±1．20％、22．41％±2．57％比0．50％±0．09％：P〈0．01）。在ACM发病过程，酒精组血浆Hcy与心肌组织MMP-9显著正相关（r=0．848，P〈0．01）。结论长期大量饮白酒可导致血浆Hcy水平显著升高，并通过增加心肌组织MMP－9的表达参与心脏重构及酒精性心肌病的发病。

Objective To explore the role of homoeysteine in the pathogenesls of alcoholic eardiomyopathy, Methods A total of 69 male Wistar rats were randomly assigned into two groups ： alcoholfed group and the control. Cardiac function was assessed by pulse Doppler. Plasma Hey levels were examined using automatic biochemical instrument （chemiluminescence）. The protein expression of MMP-9 was evaluated using immunohistochemical method, and collagen fiber of myocardium was quantitative analyzed by Masson stain. Results After heavy drinking, the LVEDd of alcohol-fed group were larger than the control group E （7.0 ± 0. 6） mm vs （5.0 ± 0. 4 ） mm, P 〈 0. 05 ] , the LVEF and FS were lower in the 4th month（52%± 8% vs 78%± 4%,31%± 3% vs 47%± 2%,P 〈 0.05）, the data changed more significantly （P 〈 0. 01 ） in the 6th month. The level of plasma Hey from alcohol-fed group was significantly higher from the 2nd month than that before the experiment [（18.1±3.1） μmol/L vs （9.8 ±2.1） μmol/L,P 〈 0. 01 ] , and it was higher in 4th month than that in 2nd month [ （ 26. 3 ± 4. 0 ）μmol/L vs （18. 1 ± 3. 1 ） μmol/L,P 〈 0. 05 ] , it was highest in 6 months. After 4-month and 6-month drinking, the expression of MMP-9 protein from alcohol group was higher than before the experiment （0. 161%±0. 019% , 0. 263%± 0. 014% vs 0. 050% ± 0. 008% , P 〈 0. 01 ）. Masson staining showed myocardial collagen of alcohol group was more after 4-month and 6-month drinking than those before the experiment （ 10. 23%± 1.20% vs 0. 50%± 0. 09% ; 22. 41% ± 2. 57% vs 0. 50% ± 0. 09% , P 〈 0. 01 ）. Plasma Hey and cardiac tissue MMP-9 is a significant positive correlation （ r = 0. 848, P 〈 0. 01 ）. Conclusion Long-term and large drink liquor can lead to plasma Hcy levels significantly increased, and participate cardiac remodeling and the pathogenesis of ACM through increasing the expression of myocardial tissue MMP-9 protein.