摘要
目的探讨心力衰竭(心衰)实验犬心房组织Ⅰ型胶原(Col Ⅰ)、基质金属蛋白酶-2(MMP-2)及其组织抑制因子(TLMP-2)的基因表达与纤维化及心房颤动(房颤)发生的关系。方法选择健康成年杂种犬14只,随机分为心室快速起搏致心衰组和健康对照组,Burst 刺激诱发房颤,Mallory 染色测定纤维化程度,RT-PCR 和免疫组化检测左右心房各基因的 mRNA 和蛋白表达。结果心衰组左室射血分数(LVEF)由(67.4±6.0)%降至(29.2±7.8)%;发生房颤及持续性房颤分别由2只和0只增至7只和5只,房颤持续时间由(0.57±0.57)s 延长至(462.12±181.43)s;左右心房纤维化程度分别增加268.8%和190.35;Col Ⅰ及 MMP-2的表达均明显上调(在左、右心房中,Col Ⅰ mRNA 和蛋白表达分别上调56.2%、132.2%和37.4%、78.0%,MMP-2则为100.0%、115.7%和65.7%、96.8%);TIMP-2的 mRNA 在左心房中下调46.3%,蛋白表达在左、右心房中均无明显改变,但 MMP-2/TIMP-2和其蛋白表达在左、右心房中分别显著升高285.3%、143.8%和106.1%、134.7%;在心衰组中,房颤持续时间与左心房纤维化程度、Col Ⅰ的基因表达量呈正相关,同时左心房MMP-2/TIMP-2比值与 Col Ⅰ的基因表达及纤维化程度呈正相关。结论心房组织 MMP-2、TIMP-2和 Col Ⅰ的基因表达改变可能是心衰时房颤发生与维持的分子机制之一,而 MMP-2/TIMP-2的失衡引起 Col Ⅰ的分子重构,可能是心衰时发生心房纤维化的重要机制之一。
Objective To study the relationship between Couagen I, MMP-2, TIMP-2 gene expression and atrial fibrosis during heart failure（HF） in dog. Methods Fourteen dogs were used and randomized into HF induced by ventrieular taehypaeing and control group. Burst atrial pacing was used to induce atrial fibrillation（AF）. And the mRNA and protein level of collagen I, MMP-2 and TIMP-2 were detected by RT-PCR and immunohistoehemical technique. Tissue samples were stained with Mallory triehrome. Results Left ventrieular ejection fraction （LVEF） decreased from （67.4 ±6.0）% to（29.2±7.8）%, the indueible rate of AF（7/7 vs 2/7） and sustained AF（5/7 vs 0/7） increased and duration of AF stabeatrial fibrillation（SAF）[（462. 12 ±181.43）s vs （0.57 ± 0. 57） s3 prolonged significantly in HF group. Atrial fibrous tissue content and atrial size of HF group were significantly greater than the controls dogs（268.8% in lefe atria and 190.3% in right atria）. The mRNA and protein level of collagen I （56.2% and 132.2% in lefe atria,37.4% and 78.0% in right atria）and MMP-2 （100.0% and 115.7% in lefe atria, 65.7% and 96.8% in right atria） increased evidently in both lefe atria and right atria, TIMP-2 mRNA decreased 46.3 % in lefe atria and had no change in right atria and that its protein had no change in both atrium, whereas the ratio of MMP-2/ TIMP-2 of mRNA and protein increased markedly in both lefe atria （285.3% and 143.8%）and right atria （106.1% and 134.7%）of HF group. SAF had a positive correlation with fibrosis and the gene level of collagen I in lefe atria, the ratio of MMP-2/TIMP-2 had a positive correlation with fibrosis and collagen I gene level in lefe atria during HF. Conclusions The changes of collagen I , MMP-2 and TIMP-2 gene expression appear to be a molecular mechanism of AF ,and the molecular remodeling of collagen I induced by regulation unbalance of MMP-2/TIMP-2 appears to be an important mechanism of atrial fibrosis during HF.
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2006年第2期141-145,共5页
Chinese Journal of Geriatrics
关键词
心房颤动
心力衰竭
基质金属蛋白酶
Atrial fibrillation
Heart failure
Matrix metalloproteinases
