摘要
目的:探讨组织蛋白酶K(cathepsin K,Cat K)在高血压性心脏病心室重塑发生发展中的表达及其活性与心肌纤维化的关系。方法:7周龄雄性Dahl盐敏感(DS)大鼠分别给予高负荷食盐(8%)或正常负荷食盐(0.3%)19周,建立高血压性心脏病心衰(H-HF)模型和对照组(19W-C)。另设人心肌活检标本作研究对象(H-HF患者10例和对照组6例)。用RT-PCR和免疫组化分别检测Cat K mRNA及蛋白表达,酶谱法测定大鼠心肌组织中的组织蛋白酶活性,心脏石蜡切片Azan染色法分析左心室肌间质和血管周围纤维化程度,细胞荧光染色法分析白介素-β1(IL-β1)对培养心肌细胞的Cat K的表达及其胶原蛋白分解能的影响。结果:H-HF组大鼠和患者心肌中的Cat K mRNA的表达显著高于19W-C组和对照组人(P<0.01)。免疫组化法和in situ法分析显示增高的Cat K mRNA和蛋白主要表达于心肌细胞。H-HF组大鼠心肌组织蛋白酶依赖性胶原蛋白分解能显著高于19W-C组。H-HF组大鼠心肌中IL-β1表达也在显著增高。IL-β1刺激心肌细胞的Cat K蛋白及其胶原蛋白分解活性。心肌中的Cat K mRNA表达与左心室肌纤维化面积呈显著正相关(r=0.68,P<0.01)。结论:在心肌中Cat K表达及分泌受IL-β1的调控,并参与高血压性心脏病的发生、发展过程,提示心肌Cat K在H-HF的心肌重塑及纤维化发展中起重要作用。
Objective： Cardiac fibrosis is characterized by tisssue remodling resulting from an imbalance between synthesis and degradation of extracellular riganic matrics. Cathepsin （Cat） K has been imphcated m extracellular matrix proteins clegraaanon during various tissue remodeling processes. The aims of this study were to investigate the expression of Cat K in left ventricular （LV） tissues, the correlation between Cat K expression and LV fibrosis, and the contribution of Cat K to cardiac myocyte- medited collagen degradation. Methods： The expression of Cat K was examined in the LV tissues of rats with hypertensive heart failure （H-HF） and control rats. Results： Reverse transcription and real-time polymerase chain reaction analysis revealed that the abundance of Cat K mRNA in the LV tissues was greater in rats with H-HF than in control rats. Immunohistochemistry revealed that Cat K was localized predominantly to cardiacmyocytes （CMCs） in H-HF rats. The Cat K-dependent collagenolytic activity in extracts of the LV tissues was markedly increased in H-HF rats. Expression levels of Cat K in the LV tissues showed a highly significant positive correlation with LV fibrosis in H-HF rats （r= 0.68, P〈0.01）. The expressions of interleukin （IL）-1β; was increased in the LV tissue of H-HF rats, and this inflammatory cyto- kine was found to increase the Cat K mRNA expression and collagenolytic cativity in cultured neonatal CMCs. Conclusion： These data suggest that Cat K may contribute to control hypertension-induced LV remodeling and fibrosis, IL-1β appears to regulate its overexpression in CMCs.
出处
《中国临床医学》
北大核心
2008年第4期449-453,共5页
Chinese Journal of Clinical Medicine
基金
2005~2006年度日本文部科学省科研基金(17590719
X.W.C)
第31届日本心脏财团优秀青年科研奖励基金(26-007508
X.W.C)
第3届日本心脏财团-Novartic循环器分子细胞研究优秀青年科研奖励基金(26-007523
X.W.C)
2007年度日本武田财团优秀青年科研奖励基金(26-007527
X.W.C)
