不同种鼠对实验脑型疟发生的影响研究

Effect of diverse donor mice used on the development of experimental cerebral malaria

目的比较昆明小鼠和C57BL/6小鼠作为种鼠对实验脑型疟模型的影响。方法分别以伯氏疟原虫ANKA株感染C57BL/6小鼠和昆明小鼠作为传代用种鼠,当种鼠原虫率为5%～15%时接种子代C57BL/6小鼠,观察两组小鼠原虫率、脑型疟发生率以及死亡率。同时,通过脑组织切片和脑部淋巴细胞的流式检测,观察两组发生脑型疟小鼠的脑部微血管中感染疟原虫红细胞和CD8+T细胞的粘附情况,另外,通过感染CD8+TKO小鼠,证实CD8+T细胞在两组小鼠发生脑型疟中的作用。结果用昆明小鼠作为种鼠的实验组的原虫率和脑型疟发生率均明显高于用C57BL/6小鼠作为种鼠的实验组,发生脑型疟小鼠的脑部组织切片发现,脑部微血管可见明显的感染疟原虫红细胞的粘附和CD8+T淋巴细胞浸润;而用昆明小鼠作为种鼠感染CD8+T细胞缺失的C57BL/6小鼠并不能诱导实验脑型疟的发生。结论与C57BL/6小鼠相比,昆明小鼠作为种鼠的实验组的脑型疟发病率更高,而且感染疟原虫红细胞和CD8+T细胞在脑部微血管内的粘附也是该脑型疟发生的主要因素,因此,更适合用于实验脑型疟模型的建立及其机制的探讨。

Objective To compare the Kunming mice（KM） and C57BL/6 mice as donor mice of experimental model of cerebral malaria （CM）. Methods Both C57BL/6 mice and Kunming mice infected by Plasmodium berghei ANKA were used as donor mice, when the parasitemia of donor mice reached 5% to 15%, infected red blood cells were transferred to the recipient mice to observe the parasitemia,incidence and mortality of CM in the two experimental groups.The adherence of parasitized red blood cells and CD8＋ T cells in the microvascular of brain through brain tissue slice exploring and FACS analysis of brain lymphocytes was observed at the same time.Morever,the role of CD8＋ T cell in the CM was confirmed by comparing the infection CD8-/- C57BL/6 mice with control. Results Parasitemia and CM incidence of mice group used KM as donor mice was significantly higher than that used C57BL/6 mice as donor mice. Parasitized red blood cells and CD8＋ T cells were found in the brain microvascular of CM mice when examining brain tisse slice,meanwhile,CD8-/- C57BL/6 mice used KM as donor mice could not induce the development of ECM. Conclusions CM morbidity of experimental group used KM as donor mice was higher than that of C57BL/6 mice as donor mice.Parasitized red blood cells and CD8＋ T cells play a centre role in the development of ECM in this model. Collectively,KM was preferred to be used to establish experimental mode of cerebral malaria and to investigate its mechanisms.