摘要
目的:通过对单纯收缩期高血压模型鼠接受骨髓间质干细胞移植干预后脉搏波传导速度及动脉壁成分变化的分析,探讨骨髓间质干细胞改善动脉顺应性的作用。方法:实验于2004-11/2005-02在武装警察部队心血管疾病研究所完成。①选择28只Wistar雄性大鼠,随机分为模型组24只,健康对照组4只。模型组复制单纯收缩期高血压模型,具体方法如下:华法林钠15mg/(kg·d)灌胃给药,1次/d,维生素K110mg/kg,皮下注射,1次/d。造模时间为6周。6周后随机选取4只模型组动物进行有创血压及血流动力学指标检测,与健康对照组比较,确定模型复制质量。②剩余模型组大鼠20只随机分为干细胞干预组11只与模型对照组9只,干细胞干预组于造模后第7周起始进行左心室直接注射同种异体干细胞,注射细胞数量为1×106/只,注射液体量为15μL/只,模型对照组注射等量磷酸盐缓冲液,4周后在体条件下检测血压及脉搏传导速度,并对动脉壁成分及血红素加氧酶、纤维黏连蛋白、骨桥蛋白等活性蛋白表达水平进行检测。结果:28只大鼠均进入结果分析。①造模组收缩压、脉压水平高于正常组[(145±11),(116±11)mmHg;(72±9),(46±5)mmHg],差异有显著性意义(P<0.05),舒张压与对照组比较差异无显著性意义(P>0.05),提示模型复制成功。②干细胞干预后4周,干预组动物脉搏波传导速度为(178.65±18.54)cm/ms,低于模型对照组(264.85±25.35)cm/ms,差异有显著性意义(P<0.01)。进一步的相关分析显示脉搏传导速度的变化与脉压变化具有正向相关性(r=0.665),与收缩压水平的变化无关。③干细胞干预组动脉壁中弹力/胶原比值大于对照组[(1.468±0.41),(1.031±0.19)],差异有显著性意义(P<0.05),中膜/管径比值与动脉重量两组比较差异无显著性意义(P>0.05),提示骨髓间质干细胞进入组织后并没有造成动脉壁中细胞成分的过度增生。④干细胞干预组纤维黏连蛋白、血红素加氧酶在动脉的表达高于对照组,骨桥蛋白的表达低于对照组。结论:骨髓间质干细胞移植治疗能够增加单纯收缩期高血压时大动脉传导速度,改善动脉壁中弹性纤维/胶原纤维的比值,改善大动脉顺应性。
AIM： To explore the effect of mesenchymal stem cells （MSCs） on ameliorating arterial compliance by analyzing the changes of pulse wave velocity （PWV） and arterial wall structure after MSCs transplantation in isolated systolic hypertension （ISH） rats. METHODS： This experiment was carried out in Institute of Cardiovascular Disease, Armed Police Forces from November 2004 to February 2005. （1）Totally 28 male Wistar rats were used as study objects and randomly divided into model group with 24 rats and healthy control group with 4 rats. The rats in the model group were selected to copy ISH model according to the method line out： 15 mg/kg warfarin sodium per day was given by gastric perfusion, once a day, 10 mg/kg vitamin K1, by hypodermic injection, once a day for 6 weeks. After model copy, 4 ISH model rats were selected to measure blood pressure and hemodynamic parameter, and compared with those in the healthy control group to define the copy mass. （2）Twenty ISH model rat left were randomly divided into MSCs intervention group with 11 rats and model control group with 9 rats. MSCs intervention group received stem cell allograft at 7^th week by left ventricular injection, and 1×10^8 cells were used for each rat, which was resolved in 15 μL fluid. Model control group received the same amount of phosphate buffer. Four weeks later, PWV and blood pressure were measured at the same time. The components of arterial wall as well as the expressions of hemeoxygenase, fibronectin and osteopontin were measured. RESULTS： Totally 28 rats were involved in the result analysis. （1）The systolic blood pressure and pulse pressure were higher in model group than normal group [（145±11）,（116±11） mm Hg;（72±9）, （46±5） mm Hg], and there were significant differences （P 〈 0.05）, but no difference was found in diastolic blood pressure as compared with the control group （P 〉 0.05）, which indicated that the ISH model were successfully copied. （2）PWV in the MSCs intervention group （178.65±18.54） cm/ms was lower than that in the model control group （264.85±25.35） cm/ms, and there were significant differences （P 〈 0.01 ）. Further study showed that the change of PWV was positively related to the change of pulse pressure（r=0.665） but had nothing to do with systolic pressure. （3）The ratio of elastic fiber to collagen fiber in the MSCs intervention group was larger than that in the control group [（1.468±0.41 ）, （1.031±0.19）], and there were significant difference （P 〈 0.05）. The medium/lumen ratio or artery weight had no difference in 2 groups （P 〉 0.05）, which suggested that MSCs graft did not caused extra proliferation in arterial wall. （4）The expressions of hemeoxygenase and fibronectin in artery were higher than those in the control group, while the expression of osteopontin was lower than that in the control group. CONCLUSION： MSCs transplantation can increase PWV in ISH, ameliorate the ratio of elastic fiber to collagen fiber in arterial wall and improve the large artery compliance.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2007年第3期494-497,501,I0004,共6页
Journal of Clinical Rehabilitative Tissue Engineering Research
