1月和6月龄mdx基因缺陷小鼠心肌病理改变与心功能变化的初步研究

The Basic Morphological and Functional Changes of Dystrophin-deficent Hearts in mdx Mice.

目的 :研究 1月和 6月龄mdx小鼠心肌病理和心功能改变。方法 :1月和 6月龄mdx小鼠各 10只 ,以同龄同数量的C5 7BL6小鼠作为正常对照 ,颈动脉插管检测动脉和左心室内的血流动力学参数 ,评价各组小鼠的死亡率、生存时间和心功能。分析小鼠心脏大体形态和组织病理改变。结果 :1月龄mdx小鼠大动脉和左心室内的血流动力学参数均与对照组无显著差异。与对照组相比 ,6月龄mdx小鼠心率显著增快 (P <0 0 5 ) ,生存时间显著缩短 (P <0 0 5 ) ,左心室内第 5分钟心率和反映收缩功能的LVPSP、dp/dt及反映最大收缩舒张能力的ΔPmax,以及反映舒张功能的 dp/dt的绝对值均显著降低或减小 (分别P <0 0 1,P <0 0 1,<0 0 5 ,<0 0 1,<0 0 1)。 1月龄mdx小鼠心重 /体重比显著低于对照组 (P <0 0 1) ,而 6月龄mdx小鼠则显著增加 (P <0 0 1)。 6月龄mdx小鼠心脏宽度和长径均显著超过对照组 (均P <0 0 1)。病理切片 1月龄mdx小鼠心肌未见损害 ,6月龄mdx小鼠心肌存在散在的细胞坏死 ,炎性细胞浸润和胶原纤维含量增加。结论 :6月龄mdx小鼠已存在心脏扩张和心肌病的病理改变 ,并开始出现心率增快。

Objective To study the basic morphological mdxmice at 1-month and 6-month ages in vivo. Method： and functional changes of dystrophin-dedicent hearts in 1-month and 6-month mdxmice ） n = 10）were involved, with the same number of C57BL6 mice at corresponds ages as control. A polythene microtube, which linked uo a computer analytic system, was inserted into right carotid artery and monitosed both aortic and left ventricular hemodynamic changes. At the same time surviwal time （ t 1 and t2, grom the microtube entering carotid artery or left ventricle （LV）uo death respectively） was recorded. The histopathology was analyzed by measuring weight and different diameters of their hearts. Heart specimens were paraffin-embedded, sliced and stained by HE and Sirius red. Re. suits： The blood pressures among four groups were not significantly different. The heart rate of 6-month mdxwas significantly faster than control （P 〈 0.05）. 6-month mdxeouldn＇t tolerate the stimulation in LV and performed shorter survival time. The 5-minute HR after microtube was inserted into LV, LVPSP and dp/dt which both indicat- ed contractile function, △Pmax, the maximal potential of heart contraction and relaxation, and the absolute value of-dp/dt, potential relaxation were decreased significantly （ P 〈 0.01, 〈 0.01, 〈 0.05, 〈 0.01, 〈 0.01, respectively）. The heartweight/bodyweight ratio of 1-month mdxwas significantly lower than control （P 〈 0.01）, but at the age of 6 months it was reversed （ P 〈 0.01 ）. The different diameters of 6-month mdxhearts were all longer than control （P 〈 0.01）. Disseminated necrosis and inflammatory cells, and increased collagen were also found in 6- month mdxhearts. Conclusion： There was a significant dilated cardiomyopathy in 6-month mdxmouse. The blood pressure of mdxat 6-month was normal, but a tachycardia was found at this age. The 6-month mdxmice could not tolerate the adventitious stimulation in left ventricle, and easy to induce heart failure.