替米沙坦对压力超负荷左心室肥厚大鼠心肌Ⅰ型胶原代谢的影响

目的:探讨压力超负荷左心室肥厚大鼠Ⅰ型胶原代谢特点及替米沙坦的干预效果。方法:24只雄性SpargueDawley大鼠随机分为假手术组(n=8)、左心室肥厚组(n=8)和替米沙坦组(n=8)。行腹主动脉缩窄术建立高血压左心室肥厚大鼠模型。各组干预4周后处死大鼠,称其体质量及左心室质量,计算左心室质量指数(LVMI)。将左心室心肌行Masson染剂染色,观察并测量其胶原容积分数(CVF)。用ELISA法检测3组大鼠血清Ⅰ型前胶原羧基端肽(PICP)及Ⅰ型胶原羧基端交联肽(ICTP)的浓度,并计算PICP/ICTP的比值,直线相关分析PICP及PICP/ICTP比值与CVF的相关性。结果:与假手术组相比,左心室肥厚组左心室质量、LVMI、CVF、血清PICP及PICP/ICTP的比值均显著升高(均P0.05);与左心室肥厚组相比,替米沙坦组左心室质量、LVMI、CVF、血清PICP、PICP/ICTP的比值均显著降低(均P0.05)。3组间的ICTP相比较,差异无统计学意义;PICP及PICP/ICTP比值均与CVF呈正相关(r值分别为0.830、0.842,均P0.01)。结论:压力超负荷左心室肥厚大鼠Ⅰ型胶原合成增加、降解相对不足,合成与降解的不平衡是造成其左心室心肌间质纤维化的原因之一。替米沙坦可以抑制Ⅰ型胶原的合成,纠正其合成与降解不平衡,从而有效地抑制及逆转心肌间质纤维化。

Effect of telmisartan on metabolism of cardiac type I collagen in rats with pressure-overloaded left ventricular hypertrophy

AIM:To explore the metabolic characteristics of type I collagen in rats with pressure-overloaded left ventricular hypertrophy and the effect of telmisartan intervention. METHODS: Twenty-four male Spargue Dawley rats were randomly divided into three groups: sham-operation group (n=8), left ventricular hypertrophy group (n=8) and telmisartan group (n=8). Abdominal aorta constriction operation was performed to construct a rat model of hypertensive left ventricular hypertrophy. Rats in each group were killed after 4 weeks of treatment. Body and left ventricular mass were weighed and left ventricular mass index (LVMI) was calculated. Left cardiac ventricle was stained with Masson and observed. The collagen volume fraction (CVF) was measured. ELISA was employed to detect serum carboxy-terminal propeptide of type I procollagen (PICP) and type I collagen carboxy-terminal cross-linked peptide (ICTP) concentration to calculate the ratio of PICP to ICTP in the three groups. Linear correlation analysis was conducted to analyze, respectively, the correlation between PICP and CVF and between the ratio of PICP to ICTP and CVF. RESULTS: Compared with those in sham-operation group, left ventricular mass, LVMI, CVF, serum PICP and the ratio of PICP to ICTP in left ventricular hypertrophy group all significantly increased (all P<0.05) and compared with those in left ventricular hypertrophy group, left ventricular mass, LVMI, CVF, serum PICP and the ratio of PICP to ICTP in the telmisartan group all significantly decreased (all P<0.05). No statistical difference was observed in ICTP among the three groups. Both PICP and the ratio of PICP to ICTP were positively related with CVF (all P<0.01). CONCLUSION: Type I collagen synthesis in rats with pressure-overloaded left ventricular hypertrophy increases and its degradation is relatively insufficient and the imbalance between synthesis and degradation is one cause of cardiac mesenchymal fibrosis. Telmisartan could inhibit the synthesis of type I collagen and improve the balance between its synthesis and degradation, which effectively inhibits and reverses the cardiac mesenchymal fibrosis.