自组装肽与温度敏感性水凝胶植入对大鼠心肌梗死后心室重构的作用及机制  

Cardioprotective effect and mechanism of post-infarction ventricular remodeling after self-assembling peptide and thermosensitive hydrogel implantation in rat myocardial infarction model

作　　者：王涛[1] 林涛[1] 任珊[1] 袁明杰[1] 李晓艳[1] 蒋学俊[1] 

机构地区：[1]武汉大学人民医院心内科武汉大学心血管病研究所,430060

出　　处：《中华医学杂志》2010年第4期259-263,共5页National Medical Journal of China

基　　金：国家“973”重点基础研究发展计划（2005CB623903）

摘　　要：目的探讨不同特性生物材料自组装肽水凝胶（RAD16-Ⅱ）与温度敏感性水凝胶（DPHP）治疗心肌梗死效果的差异及其机制。方法结扎SD大鼠冠状动脉左前降支，制作心肌梗死模型。将心肌梗死模型制作成功大鼠随机分为3组，每组15只。对照组：梗死区注射磷酸缓冲溶液；RAD16—Ⅱ组：梗死区注射RAD16－Ⅱ；DPHP组：梗死区注射DPHP；另设假手术组（10只）：仅开胸不结扎冠状动脉左前降支。20d后超声心动图检测心功能，心导管检测左心室舒张收缩压力。取心肌梗死区标本行Masson三色法染色以及抗α－平滑肌免疫组化检测，观察心室结构改变以及梗死区新生血管密度。结果DPHP组左室舒张末内径（LVEDd）显著小于RAD16－Ⅱ组[（7．9±0．9）mm比（8．9±0．8）mm，P〈0．05]，左室收缩末压力（LVESP）及左室短轴缩短率（LVFS）显著高于RAD16-Ⅱ组[LVESP（114．0±7．6）mmHg比（99．1±9．6）mmHg；INFS（25．4±5．1）％比（21．9±2．9）％，P〈0．05）]。组织学检测发现DPHP组水凝胶残留，而RAD16—Ⅱ组水凝胶则完全降解。DPHP组较RAD16-Ⅱ组梗死面积小，梗死区室壁厚度高，但新生血管密度低。结论DPHP水凝胶注射对心肌梗死后心室重构抑制作用较RAD16—Ⅱ水凝胶强，其机制与新生血管密度无关。Objective To compare the cardioprotective effect of self-assembling peptide （RAD16- Ⅱ ）and thermosensitive hydrogel DPHP （Dex-PCL-HEMA/PNIPAAm） and investigate the optimal property of hydrogel for the treatment of myocardial infarction （ MI ）. Methods MI model was induced by left anterior descending （LAD） coronary artery ligation in SD rats. The animals were randomized into three groups to receive RAD16- Ⅱ hydrogel （ n = 15 ） , DPHP hydrogel （ n = 15 ） or PBS （ phosphate buffered saline; control group n = 15） ; sham-operated rats （n = 10）, a suture was tied loosely around left coronary artery without ligating it. At Day 20 post-MI, left ventricle function was evaluated by echocardiography and cardiac catheter. Masson＇s trichrome was used for histological examination; anti-α-smooth muscle antigen （α-SMA） was applied to label the neovasculature formation in infarct area. Results The rats receiving DPHP hydrogel showed a significantly smaller left ventricle end diastolic diameter （LVEDd） and higher levels of left ventricle fraction shortening （LVFS） and left ventricle end systolic pressure （LVESP） than the rats in RAD16-1] group [ LVEDd （7.9 ±0. 9） mm vs （8.9 ±0. 8） mm] ; [ LVFS （25.4 ±5.1 ）% vs （21.9 ±2. 9）% ; INESP （ 114.0 ±7. 6） mm Hg vs （99. 1 ±9.6） mm Hg; P 〈0. 05]. Histological examination showed uncompleted degraded hydrogel in infarct area of DPHP group but not in RAD16-Ⅱ group. The animals receiving DPHP hydrogel demonstrated significantly a smaller infarct size, a higher infarct wall thickness and a lower vessel density in infarct than the animals receiving RAD16-Ⅱ hydrogel （ P 〈 0. 05 ）. Conclusion DPHP hydrogel implantation further inhibits the post-MI ventricle remodeling than RAD16- Ⅱ hydrogel implantation. The mechanism is not correlated with the vascular density in infarct area.

关 键 词：心肌梗死 水凝胶 心室复建 组织填充 

分 类 号：R542.22[医药卫生—心血管疾病]