糜酶抑制剂对自发性高血压大鼠心肌纤维化的影响

Effect of cardiac chymase inhibitor on cardiac myofibrosis in spontaneously hypertensive rats

目的观察心脏糜酶在自发性高血压大鼠(SHR)心肌组织胶原合成和心肌纤维化中的作用。方法应用病理检查、计算机分析结合逆转录-聚合酶链式反应等方法,检测SHR应用糜酶抑制剂组(ChyI组)、SHR组及对照正常血压大鼠WistarKyoto组(WKY组)收缩压、心肌胶原容积分数(CVF)、心肌血管周围胶原面积比(PVCA)和心肌糜酶及I、III型胶原mRNA表达。结果ChyI组心脏CVF、PVCA分别为(27±9)%和0.4±0.1,SHR组分别为(46±8)%和1.9±0.9,WKY组为(24±11)%和0.4±0.1,ChyI组比SHR组显著下降(P<0.01),与WKY组无显著差异。ChyI组心肌组织I、III型胶原和糜酶mRNA表达相对含量均显著低于SHR组(P<0.01),与WKY组无显著差异。应用ChyI后大鼠血压与SHR比较,无显著改变。结论心肌组织糜酶参与胶原的合成,参与细胞外基质的形成和降解,促进SHR心肌纤维化,糜酶抑制剂可能对改善心肌纤维化有益。

AIM To evaluate the role of cardiac chymase on collagen synthesis of myocardial tissue and cardiac myofibrosis in spontaneously hypertensive rats. METHODS Pathological examination and the reverse transcriptase-polymerase chain reaction were performed to determine systolic blood pressure （SBP） , collagen volume fraction （CVF）, perivascular circumferential area （PVCA） of the heart and mRNA expression of cardiac chymase, type-Ⅰ and type-Ⅲ collagen in chymase inhibitor （Chy-Ⅰ） group, spontaneously hypertensive rats （SHR） group and Wistar-Kyoto （WKY） group. RESULTS The cardiac CVF, PVCA were （27 ± 9） % and 0.4 ± 0.1 respectively in Chy-Ⅰ group vs （46±8） % and 1.9± 0.9 in SHR group and （24 ± 11 ） % and 0.4 ± 0.1 in WKY group. Cardiac chymase in Chy-Ⅰ group decreased significantly compared with SHR group （P 〈0.01, respectively） , whereas there was no significant difference between Chy-Ⅰ group and WKY group, mRNA expressions of type-Ⅰ and type-Ⅲ collagen and chymase in myocardial tissue in Chy-Ⅰ group were markedly lower than those in SHR group （P 〈 0.01, respectively）, but as much as those in WKY group. No changes were observed in systolic blood pressure after Chy-Ⅰ was employed. CONCLUSION The cardiac chymase may be involved in the for-mation and degradation of extracellular matrix in myocardial tissue and may increase cardiac myofibrosis in spontaneously hypertensive rats.