Viral infection and Cardiomyopathy: enteroviral Replication and Cardiocyte Injury in the Recipient Hearts of Dilated Cardiomyopathy and Perforin Knockout Mice with Viral Myocarditis

(A)扩张型心肌病（DCM）患者受者心脏中的肠病毒检测和细胞因子表达我们检测了30例接受心脏移植的DCM患者的心肌标本。(1)组织学半定量分析：dcm患者组织学表现为炎症细胞浸润14例（47%），纤维化18例（60%）。活动期心肌炎4例（13%）。(2)细胞因子在心脏中的表达：我们利用ABI PRISM7700分析了炎症细胞因子在受体心脏中的表达。12例DCM患者中有5例IL-1β mRNA过表达（42%），5例IL-8 mRNA过表达（42%）。12例患者中有1例（8%）IL-12p35、il - 15和IFN-γ mRNA表达升高。提示IL-1β和IL-8在DCM心肌炎症损伤中起重要作用。(B)穿孔素敲除（pfk）小鼠的实验性柯萨奇病毒B3型心肌炎我们检测了感染柯萨奇病毒B3型心肌炎的pfk和野生（C57BL/6）小鼠心肌的光镜和电镜（EM）变化。野生小鼠许多心肌细胞坏死，淋巴细胞和巨噬细胞浸润。免疫电镜观察到淋巴细胞颗粒中可见穿孔蛋白。这些淋巴细胞与心肌细胞密切接触。pfk小鼠心肌细胞坏死较野生小鼠少，但心肌细胞浸润较多。这些发现表明pfk在淋巴细胞介导的心肌损伤的发展中起重要作用。

(A) Enteroviral detection and cytokine expression in the recipient hearts from patients with dilated cardiomyopathy (DCM)We examined myocardial specimens obtained from 30 DCM patients who underwent heart transplantation.(1) Semiquantitative analysis of histological findings: histological findings showed inflammatory cell infiltration in 14DCM patients (47%) and fibrosis in 18 patients (60%). 4 patients (13%) had active myocarditis.(2) Cytokine expression in the heart: We elucidated the expression of inflammatory cytokine in the recipient hearts using the ABI PRISM7700. IL-1β mRNA was overexpressed in 5 of 12 DCM patients (42%), and IL-8 in 5 of 12 (42%). Expression of IL-12p35, IL15 and IFN-γ mRNA raised respectively in 1 of 12 patients (8%). The findings suggest IL-1β and IL-8 play significant role in the inflammatory lesion in the myocardium of DCM.(B) Experimental Coxsackievirus B3 Myocarditis in Perforin Knockout (pfk) MiceWe examined light and electron microscopic (EM) changes of the myocardium obtained from pfk and wild (C57BL/6) mice with Coxsackievirus B3 myocarditis. In wild mice many cardiocytes underwent necrosis with infiltration of lymphocytes and macrophages. By immuno EM perforin were often observed in the granules of lymphocytes. These lymphocytes showed close contact with cardiocytes. In pfk mice cardiocyte necrosis was less than in wild mice, although significant number of lymphocytes infiltrated in the myocardium. These findings suggest that pfk plays an important role in the development of lymphocyte-mediated cardiocyte injury.