川芎嗪干预心力衰竭犬心房纤维化及MMP-2与TIMP-2的mRNA表达研究

Research on Tetramethylpyrazine Phosphate Intervention for Atrial Fibrosis of Heart Failure Dogs and m RNA Expression of MMP-2 and TIMP-2

目的观察并探讨川芎嗪(TMP)治疗心力衰竭(HF)实验犬心房颤动(AF)与心房纤维化的分子机制。方法2013年9—12月,我们将健康成年杂种犬21只,随机分为正常对照组、心室快速起搏致HF组和TMP干预组,每组7例。观察TMP干预HF实验犬心房组织纤维化程度与MMP-2及TIMP-2的m RNA表达变化。结果 HF组与对照组相比,AF发生率(2/7 vs 7/7,P<0.001)及持续性AF发生率(0/7 vs 6/7,P<0.001)增加,AF持续时间[(462.1±181.4)s vs(3.24±3.56)s,P<0.001]均明显延长,左右心房纤维化程度亦明显增加[右房(8.36±1.46)%vs(2.88±0.45)%,左房(11.25±1.76)%vs(3.05±0.46)%,P<0.001]且AF持续时间与左心房纤维化程度呈密切正相关(r=0.841,P=0.018);MMP-2的m RNA表达明显上调[右房(1.16±0.40)vs(0.70±0.22),P<0.05;左房(3.08±0.76)vs(1.54±0.45),P<0.001],而左心房TIMP-2则下调明显[(2.40±0.61)vs(4.47±0.87),P<0.001]。TMP组相对于HF组,持续性AF诱发率(3/7 vs 6/7,P<0.05)明显降低,纤维化程度下降[右房(5.64±0.99)%vs(8.36±1.46)%,P<0.05;左房(5.46±1.14)%vs(11.25±1.76)%,P<0.001],而左房MMP-2的m RNA表达明显下调[(1.77±0.50)vs(3.08±0.76),P<0.01],左房TIMP-2上调明显[(3.94±0.79)vs(2.40±0.61),P<0.01]。结论TMP通过调节心房组织MMP-2与TIMP-2的m RNA表达改变并促进恢复平衡,可能是其改善HF时心房纤维化并减轻AF发作的分子机制之一。

Objective To observe and discuss the molecular mechanism of TMP in treatment of auricular fibrillation（AF）and atrial fibrosis in the heart failure experimental dogs. Methods 21 healthy adult mongrel dogs from September 2003 to December 2013 were randomly divided into the normal control group, HF group caused by ventricular tachypacing and TMP intervention group with 7 cases in each, the TMP intervention for atrial tissue fibrosis degree and m RNA expression changes of MMP-2 and TIMP-2 were observed. Results Compared with those in the HF group, the incidence of AF（2/7 vs 7/7,P〈0.001）and incidence of continuous AF（0/7 vs 6/7,P〈0.001）increased, the duration time of AF of both groups was obviously prolonged, [（462.1±181.4）s vs（3.24±3.56）s,P〈0.001], the fibrosis degree of left and right atrium also obviously increased[right atrium（8.36±1.46）% vs（2.88±0.45）%, left atrium（11.25±1.76）% vs（3.05±0.46）%,P〈0.001], and the duration time of AF had a close positive correlation with the fibrosis degree of left atrium,（r=0.841,P=0.018）, and the m RNA expression of MMP-2 in left atrium was obviously down-regulated [（1.77±0.50）vs（3.08±0.76）,P〈0.01], the MMP-2 in left atrium was obviously up-regulated[（3.94±0.79）vs（2.40±0.61）,P〈0.01]. Conclusion TMP changes and promotes rebalancing by adjusting the m RNA expression of MMP-2 and TIMP-2 in atrial tissues, and it perhaps is one of molecular mechanisms of atrial fibrosis at the time of improving HF and relieving AF attack.