摘要
目的探讨高压喷射心肌内给药的可行性以及载VEGF165、bFGF温敏型壳聚糖水凝胶对缺血心肌的促血管新生和心肌保护作用。方法健康杂种犬32只,随机均分为单纯心肌梗死(SMI)组,高压喷射生理盐水(NS)组,高压喷射温敏型壳聚糖水凝胶(Chitosan)组,高压喷射载VEGF165、bFGF温敏型壳聚糖水凝胶(Chitosan+VEGF165+bFGF)组。结扎左冠状动脉前降支制备急性心肌梗死模型后,SMI组直接关胸,NS组、Chitosan组和Chitosan+VEGF165+bFGF组在结扎线以下左室前壁行高压喷射心肌内给药8~10次,1次/cm2。术后6周取材行组织学、免疫组化检查并计算心肌梗死面积,处死动物前行血流动力学检测。结果术后6周心肌内仅有少量壳聚糖水凝胶样物质残留,其周围无明显的炎性细胞浸润;与SMI组比较,Chitosan组和Chitosan+VEGF165+bF-GF组梗死区新生血管数量增加(P<0.05),梗死面积缩小(P<0.05),左室舒张末压和左室内压最大下降速率明显改善(P<0.05)。结论高压喷射心肌内给药安全、可行;载VEGF165、bFGF温敏型壳聚糖水凝胶心肌内注射能促进梗死区血管新生,缩小梗死面积。
Objective To explore the feasibility of high-pressure injection of VEGF165-and bFGF-incorporated thermo-sensitive chitosan hydrogel into ischemic myocardium, and to observe the effects of VEGF165-and bFGF-incorporated chitosan hydrogel on promoting angiogenesis and protection of myocardium from ischemia. Methods Thirty two dogs were randomly divided into 4 groups (8 each): simple myocardial infarction (SMI) group, injection of normal saline (NS) under high pressure group, injection of chitosan hydrogel under high pressure group (Chitosan) and injection of VEGF165-and bFGF-incorporated chitosan hydrogel under high pressure group (Chitosan+VEGF165+bFGF). Acute myocardial infarction model was reproduced by ligation of the left anterior descending coronary artery. No treatment was given in SMI group. Injection of normal saline, chitosan hydrogel or VEGF165-and bFGF-incorporated chitosan hydrogel under high pressure into the infarcted myocardium was done respectively in NS group, Chitosan group and Chitosan+VEGF165+bFGF group (once per square centimeter, a total of 8 to 10 times). The animals were sacrificed 6 weeks after treatment, the hearts were harvested and sectioned for histological and immunohistochemical detection, and the infarction size was measured, hemodynamic monitoring was performed before animals were sacrificed. Results Only a little residue was found 6 weeks after chitosan hydrogel injection with no obvious infiltration of inflammatory cell. Compared with SMI group, the number of neogenetic vessels was increased, infarction size reduced, and left ventricular end-diastolic pressure and the maximum decreasing rate of internal left ventricular pressure improved in chitosan group and chitosan+VEGF165+bFGF group (P0.05). Conclusion Treatment of injection of VEGF165-and bFGF-incorporated thermo-sensitive chitosan hydrogel into ischemic myocardium under high pressure is safe and feasible, and can promote angiogenesis in infarcted myocardium and reduce infarction size.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2010年第5期499-503,共5页
Medical Journal of Chinese People's Liberation Army
基金
国家自然科学基金重点项目(30527001)
国家自然科学基金面上项目(3067087)
重庆市科技攻关计划项目(CSTS2009AB5003)