心脏糜酶活性改变在心肌肥厚患者心肌纤维化中的意义

Role of cardiac chymase in cardiac myofibrosis of patients with myocardial hypertrophy

目的:观察心脏糜酶与心肌肥厚患者心肌组织胶原合成和心肌纤维化的关系。方法:应用病理检查、放射免疫、计算机分析和逆转录-聚合酶链式反应等方法,检测心肌肥厚患者(心肌肥厚组)和正常人(对照组)心脏糜酶活性、心肌局部血管紧张素Ⅱ(Ang Ⅱ)水平、心肌胶原容积分数(CVF)、心肌血管周围胶原面积比(PVCA)及心肌组织Ⅰ型和Ⅲ型胶原mRNA表达。心脏糜酶活性和心肌局部Ang Ⅱ水平与CVF及PVCA之间的关系采用相关分析。结果:心肌肥厚组心脏糜酶活性为(0.27±0.06)kU/g蛋白,对照组为(0.12±0.06)kU/g蛋白,心肌肥厚组心脏糜酶活性明显高于对照组(P<0.01)。心肌肥厚组心肌组织匀浆液Ang Ⅱ水平为(179.3±36.1)ng/g心肌组织,对照组心肌组织匀浆液Ang Ⅱ水平为(103.2±13.6)ng/g心肌组织,心肌肥厚组心肌组织Ang Ⅱ水平明显高于对照组(P<0.01)。心肌肥厚组CVF为39.5%±9.8%,对照组为20.9%±8.2%,心肌肥厚组明显高于对照组(P<0.01);心肌肥厚组PVCA为1.98±1.05,对照组为0.41±0.12,心肌肥厚组也明显高于对照组(P<0.01)。心肌肥厚患者心肌组织Ⅰ型胶原及Ⅲ型胶原mRNA表达相对含量均明显高于正常人(均P<0.01)。心脏糜酶活性与CVF及PVCA呈明显正相关(相关系数分别为0.52和0.69,P<0.05和P<0.01)。心肌局部Ang Ⅱ水平也与CVF及PVCA呈明显正相关(相关系数分别为0.49和0.58,均P<0.05)。结论:心脏糜酶可增加胶原的合成,参与细胞外基质的形成和降解,促进心肌纤维化。

AIM： To evaluate the role of cardiac chymase on collagen synthesis in myocardial tissue and cardiac myofibrosis in patients with myocardial hypertrophy. METHODS： Using the methods of pathological examination and computer processing, the cardiac collagen volume fraction （CVF） and perivascular circumferential area （PVCA） of the heart in myocardial hypertrophy group and control group were observed. Cardiac chymase activities and cardiac local angio- tensin Ⅱ （ Ang Ⅱ） concentrations were measured by radioimmunoassay. The mRNA expressions of type Ⅰ - and type Ⅲ - collagen in myocardial tissue were analyzed using the reverse transcriptase - polymerase chain reaction. The correlation analysis was performed between the activity of cardiac chymase, cardiac local Ang Ⅱ level and the cardiac CVF, PVCA. RESULTS： Cardiac chymase activity was （0. 27 ±0.06） kU/g protein in myocardial hypertrophy group and significantly increased compared with control group [ （0. 12 ±0. 06） kU/g protein, P 〈0. 01 ]. The contents of Ang Ⅱ in cardiac local tissue were also markedly increased in cardiac tissue in myocardial hypertrophy group compared with control group [ （ 179. 3 ±36. 1 ） ng/g tissue vs （ 103.2 ± 13.6） ng/g tissue, P 〈0. 01 ]. The cardiac CVF and PVCA were 39. 5% ±9. 8% and 1.98 ± 1.05 in myocardial hypertrophy group vs 20. 9% ± 8.2% and 0.41 ± 0. 12 in control （ P 〈 0. 01, respectively）.The mRNA expressions of type Ⅰ - and type Ⅲ - collagen in myocardial tissue were markedly higher in myocardial hypertrophy group than those in control group （P 〈0.01, respectively）. Cardiac chymase activity and the cardiac local Ang Ⅱ level in myocardium tissue in myocardial hypertrophy group were positively correlated with CVF and PVCA （ r = 0. 52, 0. 69 vs r = 0. 49, 0. 58, P 〈 0.05 or P 〈 0.01, respectively）. CONCLUSION ： This study supports the hypothesis that the cardiac chymase may increase collagen synthesis and participate the formation and degradation of extracellular matrix in myocardial tissue and accelerate cardiac myofibrosis in patients with myocardial hypertrophy.