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目的 探讨Toll样受体4(TLR4)是否参与实验脑型疟的发生.方法 采用伯氏疟原虫ANKA株(P.b ANKA),以三种方式感染TLR4-/- C57BL/6小鼠和对照WT C57BL/6小鼠,分别为:模拟自然感染的按蚊叮咬、子孢子定量感染以及红内期疟原虫感染.按蚊叮咬感染和子孢子定量感染:复苏液氮冻存P.b ANKA原虫一管,腹腔注射2只C57BL/6小鼠,待小鼠原虫率增殖至5%~10%时取全血传至6只C57BL/6小鼠,供3~5日龄斯氏按蚊血餐,按蚊血餐19d后,捆绑TLR4-/- C57BL/6小鼠和WT C57BL/6小鼠供按蚊叮咬感染,或者抓取感染性按蚊解剖出蚊唾液腺获得子孢子,然后定量感染实验小鼠;红内期原虫感染:液氮复苏P.b ANKA原虫,腹腔接种2只C57BL/6小鼠, 3~4 d后取106感染疟原虫红细胞腹腔接种感染实验小鼠.结果 三种感染方式下,在原虫率上,TLR4-/-C57BL/6小鼠和WT C57BL/6小鼠原虫生长曲线接近,说明TLR4缺失后不影响P.b ANKA原虫在小鼠体内的增殖;在实验脑型疟发生率和存活率上,TLR4-/- C57BL/6小鼠和WT C57BL/6小鼠均在5~10d内全部发生脑型疟并死亡,脑型疟发生率均为100%,存活率均为0%.两组实验小鼠在原虫增殖、脑型疟发生率及存活率上均无差别.结论 TLR4不参与实验脑型疟的发生发展.“,”Objective To investigate whether Toll-like receptor 4 is involved in the development of experimental cerebral malaria.Methods Plasmodium berghei ANKA(P.b ANKA)was used to infect TLR4-/- C57BL/6 mice and WT C57BL/6 mice in 3 ways:stimulation of natural infection by mosquito bite,sporozoites quantitative infection and blood stage infection. For mosquito bite,sporozoites quantitative infection,whole blood was collected from mice with a parasitemia of 5%~10% and introduced into 6 naive C57BL/6 mice for 3~5 days old Anopheles stephensi blood meal. 19 days after feeding,TLR4-/- C57BL/6 mice and WT C57BL/6 mice were infected with infectious mosquitoes or quantitative sporozoites which came from salivary gland of infectious mosquitoes.For blood stage infection, cryopreserved P. berghei ANKA parasites were thawed and intraperitoneally injected into 2 C57BL/6 mice,and 106 parasitized red blood cells were gathered from these mice 3~4 days after infection and introduced into experimental mice.Results The growth curve of parasites in TLR4-/- C57BL/6 mice was similar to that in WT C57BL/6 mice in 3 kinds of infection. This indicated that the deletion of TLR4 did not affect the proliferation of P. berghei ANKA parasitesin vivo. All TLR4-/- C57BL/6 mice and WT C57BL/6 mice developed cerebral malaria and died in 5~10 days post infection. The incidence rate of experimental cerebral malaria was 100% and survival rate was 0% in both groups. There was no difference in parasites proliferation,incidence rate of experimental cerebral malaria and survival rate between the two groups. Conclusion TLR4 did not engaged in the development of experimental cerebral malaria.