Cardiovascular therapeutics · 2018
Fasudil exerts a cardio-protective effect on mice with coxsackievirus B3-induced acute viral myocarditis.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Dai Kezhi, Wang Yaoyao, Tai Sichao, Ni Huajing, Lian Hao, Yu Yan, Liao Weifang, Zheng Cheng, Chen Qing, Kuver Aarti, Li Jia
Аннотация
AIMS: To investigate whether there exists a cardio-protective effect of Fasudil, a selective Rho kinase (ROCK) inhibitor, in an experimental murine model of acute viral myocarditis.
METHODS: Male BALB/c mice were randomly assigned to three groups: control, myocarditis treated with placebo and myocarditis treated with Fasudil (n = 40 animals per group). Myocarditis was established by intraperitoneal injection with coxsackievirus B3 (CVB3). Twenty-four hours after infection, Fasudil was intraperitoneally administered for 14 consecutive days. Twenty mice were randomly selected from each group to monitor a 14-day survival rate. On day 7 and day 14, eight surviving mice from each group were sacrificed and their hearts and blood were obtained to perform serological and histological examinations. Expression of ROCKs, IL-17, IL-1b, TNFα, RORgt, and Foxp3 were quantified with RT-PCR. Plasma levels of TNF alpha, IL-1 beta, and IL-17 were measured by ELISA. In addition, protein levels of IL-17 and ROCK2 in cardiac tissues were analyzed with Western blot.
RESULTS: Fasudil treatment significantly increased survival, attenuated myocardial necrotic lesions, reduced CVB3 replication and expression of ROCK2 and IL-17 in the infected hearts. This treatment also imposed a T-cell subpopulation shift, from Th17 to Treg, in cardiac tissues.
CONCLUSIONS: ROCK pathway inhibition was cardio-protective in viral myocarditis with increased survival, decreased viral replication, and inflammatory response. These findings suggest that Fasudil might be a potential therapeutic agent for patients with viral myocarditis.
METHODS: Male BALB/c mice were randomly assigned to three groups: control, myocarditis treated with placebo and myocarditis treated with Fasudil (n = 40 animals per group). Myocarditis was established by intraperitoneal injection with coxsackievirus B3 (CVB3). Twenty-four hours after infection, Fasudil was intraperitoneally administered for 14 consecutive days. Twenty mice were randomly selected from each group to monitor a 14-day survival rate. On day 7 and day 14, eight surviving mice from each group were sacrificed and their hearts and blood were obtained to perform serological and histological examinations. Expression of ROCKs, IL-17, IL-1b, TNFα, RORgt, and Foxp3 were quantified with RT-PCR. Plasma levels of TNF alpha, IL-1 beta, and IL-17 were measured by ELISA. In addition, protein levels of IL-17 and ROCK2 in cardiac tissues were analyzed with Western blot.
RESULTS: Fasudil treatment significantly increased survival, attenuated myocardial necrotic lesions, reduced CVB3 replication and expression of ROCK2 and IL-17 in the infected hearts. This treatment also imposed a T-cell subpopulation shift, from Th17 to Treg, in cardiac tissues.
CONCLUSIONS: ROCK pathway inhibition was cardio-protective in viral myocarditis with increased survival, decreased viral replication, and inflammatory response. These findings suggest that Fasudil might be a potential therapeutic agent for patients with viral myocarditis.
Предметные рубрики MeSH
1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineAnimalsAnti-Inflammatory AgentsAntiviral AgentsCoxsackievirus InfectionsCytokinesDisease Models, AnimalEnterovirus B, HumanInflammation MediatorsMaleMice, Inbred BALB CMyocarditisMyocardiumNecrosisProtein Kinase InhibitorsT-Lymphocytes, RegulatoryTh1 CellsViral LoadVirus Replicationrho-Associated Kinases