机构地区:[1]华中农业大学动物医学院生猪健康养殖协同创新中心,武汉430070
出 处:《畜牧兽医学报》2020年第12期3160-3170,共11页ACTA VETERINARIA ET ZOOTECHNICA SINICA
基 金:国家科技重大专项(2016ZX08006003-004)。
摘 要:防御素是一种广泛分布于动植物中的阳离子小肽,是哺乳动物先天性免疫防御系统的重要成分,具有广谱抗菌、抗病毒和抗真菌活性。猪β防御素-2(porcineβ-defensin-2,PBD-2)是猪表达的天然防御素之一,在体外具有良好的抗菌活性。本研究旨在评价PBD-2在动物体内对重要的人兽共患病原菌猪链球菌感染的治疗效果,为评估PBD-2成为治疗性药物的潜在价值提供依据。首先,在体外检测了PBD-2对猪链球菌临床分离菌株SC-19的杀菌活性,并且在鼠源巨噬细胞(RAW264.7)上检测了PBD-2的细胞毒性。随后,选取4~6周龄,体重在18~22 g的C57雌鼠,检测了PBD-2处理组和PBS对照组小鼠(n≥6)感染猪链球菌SC-19后的存活率、组织载菌量、炎性细胞因子水平和病理变化。结果表明,PBD-2(25~200μg·mL-1)可显著地抑制猪链球菌SC-19生长(P<0.05),且抑制作用随浓度升高而增强,同时,对RAW细胞无显著的毒性作用(P>0.05)。在体内,PBD-2处理能有效降低小鼠感染猪链球菌SC-19后的死亡率,并且显著降低小鼠感染细菌后的脑、肺、脾组织和血液中的细菌载量,以及血清中炎性细胞因子IL-6、IL-12和TNF-α的水平(P<0.05)。同时,PBD-2治疗也显著降低了小鼠感染细菌后肺和脾组织的病理变化程度(P<0.05)。这些结果说明,PBD-2在体外具有良好的抗猪链球菌的活性,无显著细胞毒性,同时,在小鼠体内对猪链球菌感染具有治疗效果,提示,PBD-2具有进一步开发为治疗性药物的潜力。Defensin is a small cationic peptide widely distributed in animals and plants.It is an important component of the innate immune defense system of mammals.It has a broad spectrum of antibacterial,antiviral and antifungal activities.Porcineβ-defensin-2(PBD-2)is one of the natural defensins expressed in pigs and has good antibacterial activity in vitro.The purpose of this study is to evaluate the therapeutic effect of PBD-2 in the treatment of Streptococcus suis infection in animals and to provide more insights for evaluating the value of PBD-2 as a therapeutic drug.Firstly,the bactericidal activity of PBD-2 against S.suis clinical isolate SC-19 was measured in vitro,and the cytotoxicity of PBD-2 was tested on mouse-derived macrophages(RAW264.7).Subsequently,C57 female mice aged 4-6 weeks and weighing between 18-22 g infected with S.suis SC-19 were treated with PBD-2 or PBS(n≥6).The survival rate of mice,and the bacteria loads,inflammatory cytokine levels,and pathological changes of tissues were determined.The results showed that PBD-2(25-200μg·mL-1)could significantly inhibit the growth of S.suis SC-19 in a concentration-dependent manner(P<0.05).At the same time,PBD-2 had no significant toxic effect on RAW cells(P>0.05).The in vivo study revealed that PBD-2 treatment could effectively reduce the mortality of mice infected with S.suis SC-19.At the same time,PBD-2 treatment significantly reduced bacteria loads in brain,lung,spleen and blood of mice,and decreased the levels of inflammatory cytokines IL-6,IL-12 and TNF-αin mouse sera(P<0.05).At the same time,PBD-2 treatment also significantly alleviated the degree of pathological damages in lung and spleen tissues of mice infected with bacteria(P<0.05).These results indicate that PBD-2 confers great resilience to S.suis in vitro without significant cytotoxicity,while it also exhibits a therapeutic effect on S.suis infection in mice,suggesting that the use of PBD-2 as a therapeutic drug and substitutes for antibiotics is of an excellent prospect.
分 类 号:S855.11[农业科学—临床兽医学]
正在载入数据...
正在载入数据...
正在载入数据...
正在载入数据...
正在载入数据...
正在载入数据...
正在载入数据...