Chandrasekar B, Melby P C, Troyer D A, Freeman G L
Department of Medicine, University of Texas Health Science Center, San Antonio, USA.
Biochem Biophys Res Commun. 1996 Jun 14;223(2):365-71. doi: 10.1006/bbrc.1996.0900.
One of the hallmarks of Chagas' disease (caused by Trypanosoma cruzi) is progressive cardiomyopathy. The disease is associated with increased serum TNF-alpha levels, and TNF-alpha is known to depress cardiac function. It is, however, not known whether the cytokines are produced within the infected myocardium. One-month-old male Lewis rats were injected with cell culture-derived T. cruzi trypomastigotes and killed 15 days post-infection. As compared to normal animals, histologic analysis of infected animals revealed dense infection with amastigotes within myocytes and a minimal inflammatory infiltrate in the myocardium. Northern blot analysis of total RNA revealed no signal for IL-1beta or TNF-alpha, and a weak signal for IL-6 in the control rat hearts, and high levels of expression for the three genes in the infected rats. Western blots revealed results similar to that of mRNA levels, suggesting that, in addition to mechanical damage, infection by T. cruzi induces proinflammatory cytokine production in the myocardium itself, which may further exacerbate the pathology, and affect adversely myocardial function.
恰加斯病(由克氏锥虫引起)的一个显著特征是进行性心肌病。该疾病与血清肿瘤坏死因子-α(TNF-α)水平升高有关,并且已知TNF-α会抑制心脏功能。然而,尚不清楚这些细胞因子是否在受感染的心肌内产生。给1月龄雄性Lewis大鼠注射细胞培养来源的克氏锥虫锥鞭毛体,并在感染后15天处死。与正常动物相比,对感染动物的组织学分析显示,心肌细胞内有大量无鞭毛体感染,心肌中有少量炎性浸润。对总RNA的Northern印迹分析显示,在对照大鼠心脏中,白细胞介素-1β(IL-1β)或TNF-α无信号,IL-6有微弱信号,而在感染大鼠中这三种基因有高水平表达。蛋白质免疫印迹显示结果与mRNA水平相似,表明除了机械损伤外,克氏锥虫感染还会诱导心肌自身产生促炎细胞因子,这可能会进一步加重病理变化,并对心肌功能产生不利影响。