Jokinen Micheal P, Lieuallen Warren G, Boyle Michael C, Johnson Crystal L, Malarkey David E, Nyska Abraham
Charles River Laboratories-Pathology Associates, Durham, North Carolina, USA.
Toxicol Pathol. 2011 Aug;39(5):850-60. doi: 10.1177/0192623311413788. Epub 2011 Jul 11.
The heart is increasingly recognized as a target for toxicity. As studies in laboratory rodents are commonly used to investigate the potential toxicity of various agents, the identification and characterization of lesions of cardiotoxicity is of utmost importance. Although morphologic criteria have been established for degenerative myocardial lesions in rats and mice, differentiation of spontaneously occurring lesions from toxin-induced or toxin-related lesions remains difficult. A retrospective light microscopic evaluation was performed on the hearts of F344 rats and B6C3F(1) mice from National Toxicology Program (NTP) studies of six chemicals identified in the NTP database in which treatment-induced myocardial toxicity was present. Two previously defined myocardial lesions were observed: "cardiomyopathy" that occurred spontaneously or as a treatment-related effect and "myocardial degeneration" that occurred as a treatment-related effect. Both lesions consisted of the same basic elements, beginning with myofiber degeneration and necrosis, with varying amounts of inflammation, interstitial cell proliferation, and eventual fibrosis. This observation is indicative of the heart's limited repertoire of responses to myocardial injury, regardless of the nature of the inciting agent. A prominent differentiating factor between spontaneous and treatment-induced lesions was distribution and lesion onset. Once the respective lesions had undergone fibrosis, however, they generally appeared morphologically indistinguishable.
心脏越来越被认为是毒性作用的靶点。由于常用实验啮齿动物来研究各种药物的潜在毒性，因此心脏毒性损伤的识别和特征描述至关重要。尽管已经为大鼠和小鼠的退行性心肌损伤建立了形态学标准，但区分自发出现的损伤与毒素诱导或毒素相关的损伤仍然很困难。对来自国家毒理学计划（NTP）研究的F344大鼠和B6C3F(1)小鼠的心脏进行了回顾性光学显微镜评估，这些研究涉及NTP数据库中确定的六种化学物质，其中存在治疗诱导的心肌毒性。观察到两种先前定义的心肌损伤：自发出现或作为与治疗相关效应出现的“心肌病”，以及作为与治疗相关效应出现的“心肌变性”。两种损伤都由相同的基本成分组成，始于肌纤维变性和坏死，伴有不同程度的炎症、间质细胞增殖以及最终的纤维化。这一观察结果表明，无论刺激因素的性质如何，心脏对心肌损伤的反应模式有限。自发损伤和治疗诱导损伤之间一个显著的区分因素是分布和损伤发生时间。然而，一旦各自的损伤发生纤维化，它们在形态上通常就难以区分了。
