Li Qigui, Xie Lisa, Caridha Diana, Roncal Norma, Zeng Qiang, Zhang Jing, Zhang Ping, Hickman Mark, Read Lisa
Experimental Therapeutics Branch, Military Malaria Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue Silver Spring, MD 02910.
Mil Med. 2017 Mar;182(S1):360-368. doi: 10.7205/MILMED-D-16-00090.
The liver stages of Plasmodium parasites are important targets for the discovery and development of prophylactic drugs.
A real-time in vivo imaging system was used to determine the level of luminescence measured from firefly luciferase expression by sporozoites developing in hepatocytes in different strains of mice.
The luminescence values (photon counts/sec) measured from the anatomical liver location in the untreated mice infected with 10,000 Plasmodium berghei sporozoites were 8.15 × 10 for C57BL/6 Albino, 2.12 × 10 for C3H/HeNCrL, 0.91 × 10 for C57BL/6 WT, 0.28 × 10 for BALB/c, and 0.16 × 10 for ICR/CD-1 mice. This data suggests that the C57BL/6 Albino strain is most susceptible to luminescent photon, mainly because the less light scattering and absorption from deeper tissues and the skin in the strain of mouse. The photon count observed in black C57BL/6 wild type mice was shown to be 88.83% lower compared to C57BL/6 Albino mice. Although the highest growth rate of sporozoites in hepatocytes was found for C57BL/6 wild type mice in this study, the black skin of this mouse significantly reduced parasite-associated bioluminescence.
The minimal light scattering and absorption and also enhanced susceptibility to liver infection of C57BL/6 Albino mice makes this strain preferable sensitivity for discovery and development of prophylactic antimalarial drugs.
疟原虫的肝脏阶段是预防性药物发现和开发的重要靶点。
使用实时体内成像系统来测定不同品系小鼠肝细胞中发育的子孢子表达萤火虫荧光素酶所产生的发光水平。
感染10,000个伯氏疟原虫子孢子的未处理小鼠肝脏解剖部位测得的发光值(光子计数/秒),C57BL/6白化小鼠为8.15×10,C3H/HeNCrL小鼠为2.12×10,C57BL/6野生型小鼠为0.91×10,BALB/c小鼠为0.28×10,ICR/CD-1小鼠为0.16×10。该数据表明C57BL/6白化品系对发光光子最敏感,主要是因为该品系小鼠来自更深组织和皮肤的光散射和吸收较少。黑色C57BL/6野生型小鼠观察到的光子计数比C57BL/6白化小鼠低88.83%。尽管本研究中发现C57BL/6野生型小鼠肝细胞中子孢子的生长速率最高,但该小鼠的黑色皮肤显著降低了寄生虫相关的生物发光。
C57BL/6白化小鼠的最小光散射和吸收以及对肝脏感染的易感性增强,使其成为发现和开发预防性抗疟药物的首选敏感品系。