Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Life Sci. 2013 Jul 10;92(24-26):1186-94. doi: 10.1016/j.lfs.2013.05.010. Epub 2013 May 20.
To investigate whether losartan has protective effects in mice with chronic viral myocarditis induced by coxsackievirus B3 (CVB3).
Thirty two male Balb/c mice were intraperitoneally injected with CVB3 (10×TCID50) to induce chronic viral myocarditis (CVM). Losartan at 12.5mg/kg (n=16) or normal saline (n=16) were orally administered daily for 28 days to these mice. Uninfected mice (n=6) were used as controls. On day 29, all mice underwent anesthesia and echocardiography prior to sacrifice. Serum IL-17, IL-4, IFN-γ and TNF-α levels were measured by enzyme-linked immunosorbent assay, and cardiac tissues were histologically examined after hematoxylin & eosin staining. In addition, the effect of losartan on the virus titers in primary cultured neonatal rat cardiomyocytes infected with CVB3 was measured on Hep-2 cells at 72 h post infection.
Mice infected with CBV3 had significantly increased mortality, heart/body weight ratios, necrosis and inflammatory scores and decreased cardiac ejection fractions, compared with the controls (all P<0.05). Losartan significantly decreased mortality from 40.0% to 12.5%, heart/body weight ratios from 7.08 ± 2.17 to 4.15 ± 0.99, and necrosis and inflammatory scores from 3.33 ± 0.50 to 2.50 ± 0.65 (all P<0.05), and increased ejection fractions from 55.80 ± 9.25 to 72.31 ± 12.15 (P<0.05). Losartan significantly enhanced IL-4, and decreased IFN-γ, TNF-α and IL-17 (all P<0.05). In the in vitro experiment, losartan had no influence on virus titers.
Losartan protects mice against CVB3-induced CVM, most likely through upregulating Th2 responses, and down-regulating Th1 and Th17 responses.
探讨氯沙坦对柯萨奇病毒 B3（CVB3）诱导的慢性病毒性心肌炎（CVM）小鼠是否具有保护作用。
32 只雄性 Balb/c 小鼠经腹腔注射 CVB3（10×TCID50）诱导慢性病毒性心肌炎（CVM）。12.5mg/kg 氯沙坦（n=16）或生理盐水（n=16）每日灌胃给药 28 天。未感染的小鼠（n=6）作为对照。第 29 天，所有小鼠在麻醉后行超声心动图检查，然后处死。酶联免疫吸附试验（ELISA）检测血清白细胞介素 17（IL-17）、IL-4、干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）水平，苏木精和伊红（HE）染色后观察心肌组织病理学改变。此外，在感染后 72 小时，在 Hep-2 细胞上测量氯沙坦对感染 CVB3 的原代培养新生大鼠心肌细胞病毒滴度的影响。
与对照组相比，CBV3 感染小鼠的死亡率、心脏/体重比、坏死和炎症评分显著升高，射血分数显著降低（均 P<0.05）。氯沙坦可显著降低死亡率（从 40.0%降至 12.5%）、心脏/体重比（从 7.08±2.17 降至 4.15±0.99）、坏死和炎症评分（从 3.33±0.50 降至 2.50±0.65）（均 P<0.05），并增加射血分数（从 55.80±9.25 增至 72.31±12.15）（P<0.05）。氯沙坦可显著增加 IL-4，降低 IFN-γ、TNF-α 和 IL-17（均 P<0.05）。在体外实验中，氯沙坦对病毒滴度无影响。
氯沙坦可保护 CVB3 诱导的 CVM 小鼠，可能通过上调 Th2 反应，下调 Th1 和 Th17 反应来实现。
