Sakinah S, Priya Sivan Padma, Kumari Sharmilah, Amira Fatin, K Poorani, Alsaeedy Hiba, Ling Mok Pooi, Chee Hui-Yee, Higuchi Akon, Alarfaj Abdullah A, Munusamy Murugan A, Murugan Kadarkarai, Taib Che Norma Mat, Arulselvan Palanisamy, Rajan Mariappan, Neela Vasantha Kumari, Hamat Rukman Awang, Benelli Giovanni, Kumar S Suresh
Department of Medical Microbiology and Parasitology, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
Department of Biomedical Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
Tissue Cell. 2017 Feb;49(1):86-94. doi: 10.1016/j.tice.2016.11.005. Epub 2016 Nov 23.
In this research, we characterized the histopathological impact of dengue virus (serotype DENV-2) infection in livers of BALB/c mice. The mice were infected with different doses of DENV-2 via intraperitoneal injection and liver tissues were processed for histological analyses and variation was documented. In the BALB/c mouse model, typical liver tissues showed regular hepatocyte architecture, with normal endothelial cells surrounding sinusoid capillary. Based on histopathological observations, the liver sections of BALB/c mice infected by DENV-2 exhibited a loss of cell integrity, with a widening of the sinusoidal spaces. There were marked increases in the infiltration of mononuclear cells. The areas of hemorrhage and micro- and macrovesicular steatosis were noted. Necrosis and apoptosis were abundantly present. The hallmark of viral infection, i.e., cytopathic effects, included intracellular edema and vacuole formation, cumulatively led to sinusoidal and lobular collapse in the liver. The histopathological studies on autopsy specimens of fatal human DENV cases are important to shed light on tissue damage for preventive and treatment modalities, in order to manage future DENV infections. In this framework, the method present here on BALB/c mouse model may be used to study not only the effects of infections by other DENV serotypes, but also to investigate the effects of novel drugs, such as recently developed nano-formulations, and the relative recovery ability with intact immune functions of host.
在本研究中,我们描述了登革病毒(血清型DENV-2)感染对BALB/c小鼠肝脏的组织病理学影响。通过腹腔注射用不同剂量的DENV-2感染小鼠,并对肝脏组织进行处理以进行组织学分析,并记录变化情况。在BALB/c小鼠模型中,典型的肝脏组织显示肝细胞结构规则,肝血窦毛细血管周围的内皮细胞正常。基于组织病理学观察,感染DENV-2的BALB/c小鼠的肝脏切片表现出细胞完整性丧失,肝血窦间隙增宽。单核细胞浸润明显增加。观察到出血以及微泡和大泡性脂肪变性区域。坏死和凋亡大量存在。病毒感染的标志,即细胞病变效应,包括细胞内水肿和空泡形成,累积导致肝脏中的肝血窦和肝小叶塌陷。对致命人类登革热病例尸检标本的组织病理学研究对于阐明组织损伤以制定预防和治疗方案很重要,以便应对未来的登革病毒感染。在此框架下,此处介绍的关于BALB/c小鼠模型的方法不仅可用于研究其他登革病毒血清型感染的影响,还可用于研究新型药物的作用,例如最近开发的纳米制剂,以及宿主完整免疫功能下的相对恢复能力。