【作者】 王秀娟；

【导师】 陈波；

【作者基本信息】 黑龙江中医药大学 ， 中西医结合临床， 2004， 硕士

【摘要】 为探求AMI后，KNHX-Ⅱ扩张冠状动脉及抑制明胶酶的机理和疗效，建立了大鼠AMI模型，通过观察实验动物梗死区心肌的染色及MMP9含量的变化，并测定血浆中CGRP含量的变化来说明这一机制。结扎大鼠LAD，造模成功术后2小时，颈总动脉取血，制备血浆，采用放免法检测降钙素基因相关肽。处死大鼠后取梗死区心肌进行HE染色及免疫组化法测定金属基质蛋白酶的含量(定性分析)。通过光镜观察MI的程度。 实验证明，KNHX-Ⅱ能明显提高血浆中CGRP的含量，降低MMPs活性，并随着剂量的增加与治疗作用成正相关。 KNHX-Ⅱ防治MI机制可能是良性调节血浆中CGRP和梗死心肌内的MMP9的含量。众所周知，心脏持续射血满足全身各组织脏器供血的能力与心肌损伤的程度直接相关，AMI后常常同时伴随着冠状动脉痉挛的发生，KNHX-Ⅱ通过增加血浆中CGRP含量，舒张血管平滑肌，扩张痉挛的冠状动脉，降低心脏的负荷，保护缺血的心肌，并改善心功能。AMI后MMP9被激活，表现为梗死区心肌MMP9含量明显增加，而MMP9会导致纤维类胶原的分解破坏，左心室的扩张和心室重塑。KNHX-Ⅱ不仅能抑制MMP9的活性，也能抑制它的合成，减少ECM的降解，从而防止心室重构，保护缺血心肌和改善心功能。更多还原

【Abstract】 In order to study the mechanism and curative effectiveness of the KangNingHuXin(KNHX-II) on the AMI.we established on rats the acute myocardial infarction models to study the change of the activity of MMP9 in the necrosis zone and the levels of CGRP in the plasma of AMI rats . adult wistar rats were ligated the left descinding coronary artery, then being devided randomly into six groups: sham-operation; saline; aspirin-Kaptopril; low-dosage, normal-dosage,high-dosage group.The quantity of each group is ten. After the operation was finished,Two hours later, taking the blood in the artery to measure the CGRP. The contents of CGRP in the plasma of rats (50 AMI and 10 sham-operaton rats )were masured by the methods of radioimmunoassay. Parts of the necrosis zone in rats heart were selected for HE and immunohistochemical staining .Some of the specimens in necrosis zone of AMI rats were stained with HE to identify the ischemic or necrosis degree. Immunohistochemical method was used to measure the secretion of MMP9.we learned the results by measuring the contents of CGRP and MMP9.The results demonstrated that normal-dosage of KNHX-II,high-dosage of KNHX-II can increase the contents of CGRPand decrease the concentration of MMP9,singnificantly,the effects were enhanced with the increasing of the drugs’ concentration.The favourable regulation of plasma CGRP and MMP9 in necrosis zone is possibly one of mechanisms for KNHX-II preventing and treating AMI. As is well known to all .the ability of the heart to continue functioning as a pump relates directly tothe extent of myocardial damage. AMI is usually accompanied with coronary spasm .The mechanism of therapeutic actions of KNHX-II may be explained by its ability to increase the contents of CGRP .CGRP can relax vascular smooth muscle and cause coronary arterial dilatation, consequently ,reduce cardial preload and afterload ,reduce the work of the heart.The activity of MMP9 in the necrosis zone showed an obvious increase . The latent MMP9 were activated after infarction ,which resulted in the damage of the fibrillar network and dalitation of the left ventricle and ventricle remodeling . KNHX-II not only attenuates the activity of MMP9 but also prevents collagen synthesis, decreases the total collagon in the necrosis zone at the stage after infarction .Thus regressing the progress dysfunction of the infarction heart and protecting the ischemic myocardium.Conclusions : the KNHX-II can alleviate coronaryspasm and prevent ventricle remodeling and avoid the occurance of re-infarction after AMI. .更多还原