Basic and clinical investigation of the mechanism in the aldosterone regulation by the sympathetic system

本研究的目的是探讨基质金属蛋白酶(MMPI)抑制剂多西环素对SS激动剂诱导的心肌纤维化及基质金属蛋白酶表达的影响。将大鼠分为3组：对照组、异丙肾上腺素(ISO)组和异丙肾上腺素联合多西环素(ISO DOX)组。与对照组相比，ISO可引起心肌肥大和心肌纤维化，但与DOX合用可减轻心肌肥大和心肌纤维化。在ISO处理组中，MMP2活性也升高，但在与DOX共同处理时，其活性降低。同样，免疫印迹显示，在ISO组中，MMP-2水平显著增加，而在DOX联合治疗组中，其水平显著降低。结果提示，在β激动剂信号通路中，基质金属蛋白酶-2的表达增强在促进心肌纤维化中起着重要作用，基质金属蛋白酶抑制物可减轻心肌纤维化。

Our objectivewas to investigate the effectsof doxycycline, a matrix metalloproteinase(MMP) inhibitor(MMPi) on ss-agonist-induced myocardial fibrosis and MMP expression. Rats were divided into 3groups : control, Isoproterenol(ISO), and Isoproterenolwith doxycycline(ISO+DOX). Compared to the control, ISO induced the myocardial hypertrophyand cardiacfibrosis, but were attenuated by co-treatment with DOX. MMP-2 activity alsoincreased in the ISO treatment, but decreased by co-treatment with DOX. Similarly, immunoblotting showedsignificant increaseinMMP-2levelin the ISO, and decreased levels in the DOX co-treatment. Ourresults suggest that the enhanced expression of MMP-2plays a prominent role inpromoting myocardial fibrosis inβ-agonist signaling pathway, and that MMP-inhibiting compoundsmay attenuate myocardial fibrosis.