[氯沙坦和辛伐他汀对压力超负荷大鼠心脏胶原含量、MMP-2 mRNA、MMP-9 mRNA及TIMP-1 mRNA、TIMP-2 mRNA心肌表达的影响]

[Effects of losartan and simvastatin on collagen content, myocardial expression of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in pressure overload rat hearts].

作者信息

Xing Xiao-qian, Xu Jian, Lü Xiong-wen, Huang Yan, Zhu Peng-li

机构信息

Department of Cardiology, The Affiliated Provincial Hospital of Anhui Medical University, Hefei 230001, China.

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2009 Oct;37(10):887-91.

PMID:20137537

Abstract

OBJECTIVE

To investigate the effects of simvastatin(Sim) and losartan(Los) on cardiac fibrosis and myocardial expression of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in pressure overloaded rat hearts.

METHODS

The pressure overload model was induced by descending aortic constriction (DAC) in rats. SD rats were randomized into 6 groups (n = 20 each): normol control group, control sham group, DAC group, Los group (DAC + Los, 5 mg/kg), Sim group (DAC + Sim, 2 mg/kg), Los + Sim group (DAC + Los + Sim, Los 5 mg/kg, Sim 2 mg/kg). Water, Los or Sim drug was administrated by gavage daily beginning from day 5 after operation for 30 days. Collagen was measured on Masson stained myocardial sections, and the level of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in left ventricle were detected by RT-PCR.

RESULTS

Collagen volume fraction (CVF) in DAC group was significantly higher than the normal control and sham groups (P < 0.01) which could be significantly reduced by Los and Sim (P < 0.05), especially in DAC + Los + Sim group (P < 0.01). The levels of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA were also significantly higher in DAC group than in normal control and sham groups (P < 0.01). Treatment Sim and Los alone and especially in combination significantly decreased the TIMP-1 mRNA, TIMP-2 mRNA expressions (P < 0.01) while MMP-2 mRNA, MMP-9 mRNA levels remained unchanged (P > 0.05).

CONCLUSION

Upregulation of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA expressions might contribute to myocardial fibrosis in this model, Sim and Los significantly inhibited myocardial fibrosis possibly by downregulating myocardial TIMP-1 mRNA, TIMP-2 mRNA expressions in this model.

摘要

目的

研究辛伐他汀（Sim）和氯沙坦（Los）对压力超负荷大鼠心脏心肌纤维化及基质金属蛋白酶-2（MMP-2）mRNA、基质金属蛋白酶-9（MMP-9）mRNA、金属蛋白酶组织抑制因子-1（TIMP-1）mRNA和金属蛋白酶组织抑制因子-2（TIMP-2）mRNA表达的影响。

方法

采用腹主动脉缩窄（DAC）法建立大鼠压力超负荷模型。将SD大鼠随机分为6组（每组n = 20）：正常对照组、假手术对照组、DAC组、氯沙坦组（DAC + Los，5 mg/kg）、辛伐他汀组（DAC + Sim，2 mg/kg）、氯沙坦+辛伐他汀组（DAC + Los + Sim，Los 5 mg/kg，Sim 2 mg/kg）。术后第5天开始每天经口灌胃给予水、氯沙坦或辛伐他汀药物，持续30天。对Masson染色的心肌切片进行胶原含量测定，采用逆转录聚合酶链反应（RT-PCR）检测左心室中MMP-2 mRNA、MMP-9 mRNA、TIMP-1 mRNA和TIMP-2 mRNA的水平。

结果

DAC组的胶原容积分数（CVF）显著高于正常对照组和假手术对照组（P < 0.01），氯沙坦和辛伐他汀可使其显著降低（P < 0.05），尤其是在DAC + Los + Sim组（P < 0.01）。DAC组心肌MMP-2 mRNA、MMP-9 mRNA、TIMP-1 mRNA和TIMP-2 mRNA水平也显著高于正常对照组和假手术对照组（P < 0.01）。单独使用辛伐他汀和氯沙坦治疗，尤其是联合使用时，可显著降低TIMP-1 mRNA和TIMP-2 mRNA的表达（P < 0.01），而MMP-2 mRNA和MMP-9 mRNA水平保持不变（P > 0.05）。