盐酸小檗碱对大鼠心肌梗死模型心室重塑的作用研究

摘要

Objective: To study the effect of berberine (BR) on ventricular remodeling in experimental rats with myocardial infarction (MI) and its mechanisms. Methods: The MI model of experimental rats was established by ligation of the left anterior descending coronary artery and the MI animals were randomly divided into 3 groups: MI+BR group, in which the rats received BR 20 mg/kg.d, Sham group and MI group, the rats in those 2 groups received the same volume of normal saline. All animals were treated for 8 weeks. The cardiac function and structure were assessed by echocardiography, cardiac interstitial collagen deposition was evaluated by Masson stain, the myocardial cell apoptosis was detected by Tunel method, and the activation of nuclear factor (NF-κB) was also examined. Results: For echocardiography, MI group had enlarged left ventricular end diastolic diameter (7.28 ± 0.29) mm than Sham group (6.86 ± 0.36) mm,P<0.05, but it decreased in MI+BR group (6.89 ± 0.99) mm,P>0.05. MI group had increased left ventricular end systolic diameter (5.88 ± 0.33) mm than Sham group (4.61 ± 0.31) mm, but it decreased in MI+BR group (4.68 ± 1.17) mm, allP< 0.01. MI group showed increased left ventricular posterior wall compensatory hypertrophy (1.81 ± 0.85) mm than Sham group (1.67 ± 0.16 mm),P<0.05, while in MI+BR group, it was deereased to (1.65 ± 0.14) mm. MI group presented decreased LVEF (45.77 ± 3.17) % than Sham group (67.28 ± 4.15) %, but it increased in MI+BR group (64.64 ± 5.82) %, allP<0.01. For Masson stain, cardiac interstitial collagen deposition in MI group (11.39 ± 0.45) % was higher than Sham group (2.65 ± 0.45) %, but less in MI+BR group (7.00 ± 0.87) %, allP<0.01. For Tunel examination, the myocardial cell apoptosis index was increased in MI group (21.31 ± 2.34) than Sham group (0.99 ± 0.38), but decreased in MI+BR group (14.15 ± 1.62), allP<0.01. For NF-κB activation study, the nuclear protein p65 content was higher in MI group (0.14 ± 0.02) ng/ml than Sham group (0.06 ± 0.01) ng/ml, but lower in MI+BR group (0.10 ± 0.02) ng/ml, allP<0.01. Conclusion: Application of BR may improve the ventricular remodeling and cardiac function in experimental MI rats, it might be because of BR partially inhibit NF-κB activation, reduce collagen deposition and help anti-apoptosis in myocardial cells.%目的：研究盐酸小檗碱对大鼠心肌梗死（心梗）模型心室重塑的作用并探讨其机制。　　方法：采用冠状动脉结扎法复制大鼠心梗模型，建好模型随机分为两组，心梗对照组和盐酸小檗碱组，同时设立假手术组。盐酸小檗碱组大鼠每日灌胃给予盐酸小檗碱20 mg/kg，假手术组和心梗对照组每日给予同等剂量生理盐水。8 W后超声心动图检测大鼠心功能和心脏结构，马松（Masson）染色法检测心肌间质胶原容积分数，Tunel法检测心肌细胞凋亡情况，并检测心肌细胞核因子-κB活化情况。　　结果：超声心动图检测结果显示，心梗对照组与假手术组相比，左心室舒张末期内径（LVDd）扩大[（7.28±0.29） mm比（6.86±0.36）mm，P <0.05]、左心室收缩末期内径（LVDs）扩大[（5.88±0.33）mm比（4.61±0.31）mm，P <0.01]、左心室后壁收缩末期厚度(LVPWTs)增厚[（1.81±0.85）mm比（1.67±0.16）mm，P <0.05]，左心室射血分数（LVEF）下降[（45.77±3.17）%比（67.28±4.15）%，P <0.01]；盐酸小檗碱组与心梗对照组相比：LVDs[（4.68±1.17）mm]缩小，LVPWTs[（1.65±0.14）mm]下降，LVEF[（64.64±5.82）%]增加，差异均有统计学意义（P均<0.01）；而LVDd[（6.89±0.99）mm]缩小，差异无统计学意义（P>0.05）。Masson染色结果显示，心梗对照组与假手术组相比，胶原容积分数增加[（11.39±0.45）％比（2.65±0.45)％，P <0.01]，盐酸小檗碱组[（7.00±0.87）％]较心梗对照组减少（P <0.01）。Tunel实验结果显示，心梗对照组与假手术组相比，心肌细胞凋亡指数增加（21.31±2.34比0.99±0.38，P <0.01），盐酸小檗碱组（14.15±1.62）较心梗对照组减少（P <0.01）。核因子-κB活化情况检测结果示，术后8 W时，心梗对照组与假手术组相比，细胞核内的p65含量增加[（0.14±0.02）ng/ml比（0.06±0.01） ng/ml]，盐酸小檗碱组[（0.10±0.02）ng/ml]较心梗对照组减少。差异均有统计学意义（P <0.01）。　　结论：盐酸小檗碱可改善大鼠心梗模型心室重塑和心功能，其机制考虑与其部分抑制心肌细胞核因子-κB活化、降低非心梗区心肌间质胶原沉积、抗心肌细胞凋亡有关。