观察6-羟多巴胺或颈交感神经节切除术制备去心脏交感神经自发性高血压大鼠模型心肌肥厚与心肌纤维化的变化

Changes of myocardial hypertrophy and myocardial fibrosis in spontaneously hypertensive rats with cardiac sympathectomy induced by 6-hydroxydopamine or cervical sympathectomy

  • 摘要: 目的 观察6-羟多巴胺(6-hydroxydopamine,6-OHDA)或颈交感神经节切除术制备去心脏交感神经自发性高血压大鼠(spontaneously hypertensive rats,SHR)模型心肌肥厚与心肌纤维化的变化。方法 选用7周龄SPF级同源同系雄性SHR 30只,随机分为3组:假手术组10只,手术组10只,6-OHDA组10只,均饲养7周。超声心动图检测心脏结构与功能,并计算左心室质量指数。生物医学信号采集处理系统检测血流动力学指标。实时定量PCR检测心肌组织Ⅰ型胶原蛋白(CollagenⅠ)、Ⅲ型胶原蛋白(CollagenⅢ)和结缔组织生长因子(connective tissue growth factor,CTGF)。结果 免疫组化结果显示,与假手术组比较,6-OHDA组与手术组酪氨酸羟化酶表达明显降低(5.34±0.32)% vs (2.17±0.28)%和(1.06±0.24)%,P均<0.05,但后两组间差异无统计学意义(P=0.547)。收缩压与心率在假手术组、6-OHDA组、手术组中依次降低,舒张压依次升高,组间差异均有统计学意义(P均<0.001)。与假手术组比较,手术组与6-OHDA组大鼠左心室质量指数、室间隔及左心室后壁厚度、左心室舒张末内径、收缩末内径明显减低(P均<0.05),大鼠心肌纤维化标记物CollagenⅠ、CollagenⅢ和CTGF基因表达也显著降低(P均<0.05),但手术组与6-OHDA组无统计学差异(P>0.05)。结论 腹腔注射6-OHDA法与手术方法去心脏交感神经SHR心肌肥厚与心肌纤维化程度均明显减轻。6-OHDA建立的化学性去交感神经模型可作为不能耐受交感神经节切除手术的一种替代方法。

     

    Abstract: Objective To study the changes of myocardial hypertrophy and myocardial fibrosis in spontaneously hypertensive rats (SHR) with cardiac sympathectomy induced by 6-hydroxydopamine (6-OHDA) or cervical sympathectomy. Methods Thirty 7-week-old male SHRs were randomly divided into three groups:sham operation group (n=10),operation group (n=10) and 6-OHDA group (n=10) and they were reared for 7 weeks.The cardiac structure and function were measured by echocardiography,and left ventricular mass index was calculated.Biomedical signal acquisition and processing system was used to detect hemodynamic parameters.CollagenⅠ,CollagenⅢ and connective tissue growth factor (CTGF) were detected by real-time quantitative PCR. Results Compared with sham operation group,tyrosine hydroxylase (TH) expression decreased significantly in 6-OHDA group and operation group (2.17±0.28)% and (1.06±0.24)% vs (5.34±0.32)%;P<0.05,respectively,and no significant difference was found between 6-OHDA group and operation group (P=0.547).Systolic blood pressures and heart rates in sham operation group,operation group and 6-OHDA were in a decreasing manner (all P<0.001),with significant differences between any of the two groups.Compared with sham operation group,left ventricular mass index (LVMI),thickness of ventricular septum,left ventricular posterior wall,left ventricular end-diastolic and end-systolic diameters were significantly lower in operation group and 6-OHDA group (P<0.05);also,the expressions of myocardial fibrosis markers CollagenⅠ,CollagenⅢ and CTGF genes were significantly lower (P<0.05);however,there was no significant difference in these indicators between the latter two groups. Conclusion Myocardial hypertrophy and myocardial fibrosis in SHR with cardiac sympathectomy are alleviated significantly by injecting 6-OHDA or cervical sympathectomy.The chemical sympathetic denervation model established by 6-OHDA can be used as an alternative method for those who are intolerant to sympathectomy.

     

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