中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (12): 2132-2136.doi: 10.3969/j.issn.1673-8225.2010.12.011

• 药物控释材料 drug delivery materials • 上一篇    下一篇

高压喷射心肌打孔及孔道内填充温敏型壳聚糖水凝胶对孔道的影响

熊  鹿，黄  晶，周大燕，郭  睿   

  1. 重庆医科大学附属第二医院心内科，重庆市  400010
  • 出版日期:2010-03-19 发布日期:2010-03-19
  • 通讯作者: 黄 晶，硕士，博士生导师，重庆医科大学附属第二医院心内科，重庆市 400010 huangjing_9901@yahoo.com.cn
  • 作者简介:熊 鹿★，男，1984年生，四川省资中县人，汉族，重庆医科大学心血管内科在读硕士，主要从事心肌再生治疗的研究。 604080761@qq.com
  • 基金资助:

    课题获得国家自然科学基金重点项目（30527001）及面上项目（3067087)，重庆市科技攻关重点项目(CSTS2005AA5008-5)资助。

Transmyocardial high-pressure injection revascularization combined with thermo-sensitive chitosan hydrogel effects on channels

Xiong Lu, Huang Jing, Zhou Da-yan, Guo Rui   

  1. Department of Cardiology, Second Hospital Affiliated to Chongqing Medical University, Chongqing   400010, China 
  • Online:2010-03-19 Published:2010-03-19
  • Contact: Huang Jing, Master, Doctoral supervisor, Department of Cardiology, Second Hospital Affiliated to Chongqing Medical University, Chongqing 400010, China huangjing_9901@yahoo.com.cn
  • About author:Xiong Lu★, Studying for master’s degree, Department of Cardiology, Second Hospital Affiliated to Chongqing Medical University, Chongqing 400010, China 604080761@qq.com
  • Supported by:

    the National Natural Science Foundation of China (Key Program), No. 30527001*, (General Program) No. 3067087*; the Tackle Key Program in Science and Technology of Chongqing City, No. CSTS2005AA5008-5*

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摘要：

背景：大量研究表明透室壁性心肌血管重建能有效治疗难治性心绞痛和终末期冠心病，但心肌血运重建后透室壁性心肌孔道不能保持长时间通畅，容易闭合，从而限制了该技术的应用。
目的: 认识高压喷射心肌打孔联合孔道内填充温敏型壳聚糖水凝胶对孔道的影响，以及该治疗方法对急性心肌梗死犬的血管新生及心肌的保护作用。
方法: 将Injex无针注射器经适当改造后制作成高压喷射系统；由壳聚糖盐酸盐、β-甘油磷酸钠和羟基乙基纤维素按照一定的浓度比配制成温敏型壳聚糖水凝胶。健康杂种犬24只随机均分为3组：①单纯心肌梗死组制模成功后直接关胸。②心肌打孔+水凝胶组将壳聚糖水凝胶于结扎线以下左室前壁行高压喷射透壁性心肌打孔8~10个(1孔/cm2)。③心肌打孔组用等体积生理盐水于相同部位行心肌打孔。6周后行血流动力学检测，计算微血管密度和心肌梗死面积，行苏木精-伊红染色观察孔道通畅情况，天狼猩红染色检测胶原增生情况并计算Ⅰ、Ⅲ型胶原比值。
结果与结论： ①术后6周，心肌打孔组孔道明显缩小，部分节段已完全闭塞；心肌打孔+水凝胶组孔道仍未闭塞,开放直径100~300 μm,部分节段已内皮化。②与单纯心肌梗死组比较，心肌打孔组和心肌打孔+水凝胶组促进了梗死区血管新生，且心肌打孔+水凝胶组缩小了梗死面积，在一定程度上改善了左室重塑。提示高压喷射心肌打孔联合孔道内温敏型壳聚糖水凝胶填充有助于保持孔道的通畅，能促进孔道周围血管新生，缩小梗死面积，具有改善左室重塑的作用，是治疗心肌梗死的一种可行的方法。

关键词: 高压喷射, 孔道, 壳聚糖水凝胶, 心肌梗死, 血管新生

Abstract:

BACKGROUND: Many experiments have suggested that transmyocardial revascularization (TMR) is effective in refractory angina pectoris and end-stage coronary artery disease. The main problem for TMR, however, is occlusion of the transmural channels, which limits the application of the technology.
OBJECTIVE: To explore the impact of transmyocardial high-pressure injection revascularization combined with thermo-sensitive chitosan hydrogel filled the channels on channel’s patency and the effect of promoting angiogenesis and myocardial protection on acute myocardial infarction.
METHODS: High-pressure injection system, Injex needle-free syringe was made by the appropriate transformation of post-production. Thermo-sensitive chitosan hydrogel was made of chitosan hydrochloride, β-glycerol phosphate and hydroxyethyl cellulose prepared in accordance with a certain concentration ratio. A total of 24 healthy hybrid dogs were randomly assigned to three groups. In the simple myocardial infarction group (SMI), acute myocardital infarction models were made by ligation of the left anterior descending coronary artery. No treatment was given in SMI group. In the transmyocardial high-pressure injection revascularization group (TMIR) with thermo-sensitive chitosan hydrogel group (TMIR+chitosan), transmyocardial high-pressure injection revascularization was performed on infarct myocardium and about 8 to 10 transmural channels were created in ischemic area, one channel per square centimeter. In the TMIR group, the same volume saline was used in the identical site. Hemodynamics, capillary density and myocardial infarct size were detected at 6 weeks after treatment. Hematoxylin and eosin staining and Sirius red staining were used to detect channel patency and collagenous fiber proliferation, and the ratio of type Ⅰ, Ⅲ collagen was calculated. 
RESULTS AND CONCLUSION: The channels in TMIR group had significantly narrowed; some segments had been completely occluded. However, channels in TMIR + chitosan group had not been occluded, the opening diameter was about 100-300 μm; some segments had been endothelialization. Compared with the SMI group, TMIR group and TMIR + chitosan group promoted angiogenesis in the infarct area, and TMIR + chitosan group reduced the infarct size and improved left ventricular remodeling. These indicated that transmyocardial high-pressure injection revascularization combined with thermo-sensitive chitosan hydrogel filled the channels is helpful to maintain the channel patency and can promote angiogenesis around the channels, reduce infarct size and improve left ventricular remodeling. It may be a viable approach in the treatment of myocardial infarction.

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