Cocaethylene and heart disease during murine AIDS.
Cocaethylene and heart disease during murine AIDS.
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小鼠艾滋病期间的可卡乙烯和心脏病。
DOI：
10.1016/s1567-5769(01)00157-6
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Watson,RonaldRoss
中科院分区：
文献类型：
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作者：
Liu,Yingying;Montes,Sergio;Zhang,Dongqin;Sepulveda,RamonTomas;Yu,Qianli;Zhang,Jin;Larson,DouglasF;Watson,RonaldRoss
可卡因乙烯是一种活性可卡因代谢物，据信在同时服用酒精和可卡因的个体中心脏性猝死的发生率增加中起着致病作用。长期和过度滥用可卡因和酒精将导致宿主免疫力的显著改变，从而增加对感染的易感性。为了检测可卡因对心脏功能的慢性直接影响，在本研究中使用了电导导管系统（CCS）。为了测试在小鼠AIDS期间可卡因注射是否加重柯萨奇病毒B3（CVB 3）或巨细胞病毒（CMV）心肌病，用LP-BM 5逆转录病毒感染雌性C57 BL/6小鼠，并用CVB 3或CMV进行超感染。每天给小鼠腹膜内注射溶于0.9%盐水溶液中的古柯乙烯（浓度从15 mg/ml逐渐增加至25 mg/ml）。对各组大鼠心脏组织进行组织病理学分析，并对CMV感染组大鼠脾脏细胞因子进行检测。结果表明，注射可卡因对心血管系统无明显影响。在小鼠逆转录病毒感染期间注射可卡因大大加剧了CVB 3或CMV感染的发病机制，而CMV感染的小鼠与CVB 3感染相比表现出相对温和的心脏病理学。CMV和逆转录病毒感染均抑制Th 1应答。我们的数据表明，古柯叶治疗转移细胞因子的平衡，特别是抑制Th 1反应，促进增加CVB 3或CMV诱导的心肌炎。
Cocaethylene is an active cocaine metabolite believed to play a causative role in the increased incidence of sudden cardiac death in individuals who co-administer alcohol and cocaine. Prolonged and excessive abuse of cocaine and alcohol will result in marked alteration of host immunity to increased susceptibility to infection. To test the chronic direct effect of cocaethylene on the heart function, a conductance catheter system (CCS) was used in vivo in this study. To test whether cocaethylene injection exacerbates coxsackievirus B3 (CVB3) or cytomegalovirus (CMV) cardiomyopathy during murine AIDS, female C57BL/6 mice were infected with LP-BM5 retrovirus and superinfected with CVB3 or CMV. Daily, mice were injected intraperitoneally with cocaethylene in 0.9% saline solution (concentration increased gradually from 15 to 25 mg/ml). Histopathology of heart tissue was analyzed in all groups, and cytokines of spleen were measured in the CMV-infected groups. Results showed there was little effect on the cardiovascular system after cocaethylene injection. Cocaethylene injection during murine retrovirus infection greatly exacerbated the pathogenesis of CVB3 or CMV infection, whereas CMV-infected mice showed relatively moderate cardiac pathology compared with CVB3 infection. Both CMV and retrovirus infection suppressed the Th1 response. Our data suggest that cocaethylene treatment shifts the cytokine balance and suppresses Th1 response particularly, facilitating increased CVB3- or CMV-induced myocarditis.