特莫普利上调心肌硫氧化还原蛋白表达减轻心肌炎

目的 特莫普利是否能通过加强氧化还原调节机制减轻心肌炎。方法 Lewis大鼠自身免疫性心肌炎及离体培养的心肌细胞,免疫杂交检测特莫普利治疗前后硫氧化还原蛋白(TRX)表达,及其对心肌炎的影响。结果 特莫普利加强心肌细胞胞质定位的TRX表达,但对线粒体定位的TRX2表达则无明显改变。超氧化物歧化酶表达也无明显变化。特莫普利治疗从第1。21天,可减轻心肌炎的严重程度和降低氧化蛋白含量;但治疗从第15-21天,则无明显效果。本组心肌炎模型炎症大致从第15天开始,到21d达高峰,特莫普利从第1-21天治疗,可看做有2周的预治疗来上调心肌细胞TRX表达,通过加强TRX表达减轻心肌炎症。结论 TRX和经TRX修饰的氧化还原状态在自身免疫性心肌炎的发病中起重要作用,特莫普利治疗通过加强心肌TRX表达减轻心肌炎症。

Temocapril treatment upregulated cardiomyocyte thioredoxin expression and improved autoimmune myocarditis

OBJECTIVE: Thioredoxin (TRX) is a redox regulatory protein that protects cells from various stresses. Angiotensin-converting enzyme (ACE) inhibitor was reported to enhance endogenous antioxidant enzyme activities. This study was carried out to investigate whether temocapril, a novel non-sulfhydryl containing ACE inhibitor, reduces the severity of myocarditis via redox regulation mechanisms involving TRX. METHODS: The up-regulation of TRX by temocapril treatment was checked by Western blot in normal rat myocytes in vitro and in vivo, as well as in rats with experimental autoimmune myocarditis (EAM). RESULTS: Temocapril enhanced cytosolic redox regulatory protein TRX expression, but neither mitochondrial TRX2 nor antioxidant enzymes, such as copper-zinc superoxide dismutase (Cu/Zn-SOD) or manganese superoxide dismutase (Mn-SOD) expression, was up-regulated by the preconditioning treatment. In rats with EAM, the severity of myocarditis and the protein carbonyl contents were less increased in temocapril treatment (10 mg x kg(-1) x d(-1), orally) from day 1 to day 21, but not in temocapril treatment from day 15 to day 21. If the characteristics of this model that myocardial inflammation begins around day 15 and keeps on until day 21 is considered, temocapril treatment for 3 weeks might be thought as a preconditioning treatment. CONCLUSIONS: TRX and the redox state modified by TRX may play a crucial role in the pathophysiology of EAM. Temocapril ameliorates myocarditis with inducing TRX up-regulation in a preconditioning manner, although the mechanism of TRX up-regulation by temocapril remains to be elucidated.