摘要
目的 观察过表达eNOS的骨髓间充质干细胞移植对高血流性肺动脉高压的作用.方法 构建过表达eNOS基因骨髓间充质干细胞.成年雄性Wistar大鼠,采用左侧颈总动脉与颈外静脉吻合法建立模型36只,分3组,即Shunt组、MSCs组和MSCs＋eNOS组,每组12只;正常大鼠12只为Control组.由中心静脉注入细胞,2周后测定血流动力学指标、 心肌质量变化及肺组织切片的病理变化,western blot及荧光定量PCR测定肺组织表达eNOS的变化.结果 细胞移植2周后肺组织中有eNOS表达;转染eNOS组表达eNOS mRNA和蛋白明显增加.MSCs组右心室收缩压较分流组下降[（31.9±2.4）mm Hg比（35.6±3.9）mm Hg],MSCs＋eNOS组下降更明显[（28.2±2.8）mm Hg比（35.6±3.9）mm Hg]（P〈0.05）.右心室肥厚指数分流组下降0.3411±0.0314,MSCs组下降0.3095±0.0231,两者相比差异有统计学意义;MSCs＋eNOS组下降0.2868±0.0167,与MSCs组相比未见统计学差异.MSCs组肺组织病理改变减轻,肺小动脉中层变薄,而MSCs＋eNOS组最明显.结论 MSCs可定植于肺组织并表达eNOS;MSCs移植对高血流量的肺动脉高压发挥治疗作用,联合转染eNOS进一步增加治疗效果.
Objective To observe effects of MSCs over-expressing eNOS on PAH rats of high flow blood. Methods Lentivirus expressing eNOS gene were constructed and transfected to MSCs to be transplanted. Adult male Sprague Dawley rats, with anastomosis of the left common carotid artery and left external jugular vein, were randomly divided into three groups： group shunt, group MSCs and group MSCs＋eNOS （n=12, respectively）. The control group was matched normal rat. MSCs or equal volume PBS were injected through right external jugular vein. Two weeks later, hemodynamic index, pathological changes of myocardial tissue and lung biopsy were determined. Fluorescence quantitative PCR （FQ-PCR）and Westernblot were used to determine the level of mRNA and protein of eNOS were determined. Results ENOS can be detected in rat lungs after cell transplantation. And there were high eNOS protein expression in group MSCs＋eNOS, but poor in the other three groups. The RVSP decreased from （35.6±3.9）mm Hg in the group shunt to （31.9±2.4）mm Hg in the group MSCs and to （28.2±2.8）mm Hg （P〈0.05） in the group MSCs＋eNOS （P〈0.05）. Right ventricular hypertrophy index significantly reduced from 0.3411± 0.0314 in the group shunt to 0.3095±0.0231 in the group MSCs and to 0.2868±0.0167 in the group MSCs＋eNOS （P〈0.05 respectively）, but there was no statistical significance between the latter groups. RVSP and lung′s lesions were attenuated and pulmonary medium wall was thinner in group MSCs, while these were thinnest in group MSCs＋eNOS. Conclusion MSCs can locate in rat lungs and express eNOS after cell transplantation. MSCs trans-plantation has therapeutic effects on PAH of high blood flow and ransfected eNOS can further improve the effects.
作者
赵科研
郭晓东
李红岩
佟昌慈
张玉彪
王辉山
侯明晓
ZHAO Ke-yan GUO Xiao-dong LI Hong-yan et al(Department of Cardiovascular Surgery, General Hospital of Shenyang Military District, Shenyang 110840, China)
出处
《中国心血管病研究》
CAS
2017年第7期667-670,共4页
Chinese Journal of Cardiovascular Research
基金
辽宁省自然科学基金（项目编号：2015010421-301）
