Transgenic mice expressing human sickle hemoglobin are partially resistant to rodent malaria

The polymorphic frequency of the gene for beta s-globin involved in the generation of sickle trait and sickle cell anemia in the human population is caused by the enhanced resistance of sickle trait individuals to Plasmodium falciparum malaria, as supported by epidemiologic and in vitro studies. However, the mechanism for the protective effect of sickle hemoglobin in vivo has not been fully defined. The generation of transgenic mice expressing high levels of human beta s- and alpha-chains has allowed us to study this phenomenon in vivo in an experimental model. We infected the transgenic beta s mice with two species of rodent malaria and found a diminished and delayed increase in parasitemia as compared with controls. This is in contrast to our previous studies involving the introduction of a beta A transgene, which does not alter the infection. The use of this model allowed us to address the question of the mechanism of protection against malaria in mice expressing sickle hemoglobin. We find that splenectomy of transgenic mice completely reverses the protection against Plasmodium chabaudi adami infection. The results reported have shown a relationship between the presence of the beta s gene product and partial resistance to malaria in an experimental model in vivo and shows that the spleen plays an important role in this protection.     

非转流小型猪原位肝移植模型的建立及评价

目的:建立标准化程度高、重复性和稳定性好的小型猪原位肝移植模型。方法:实验于2004-06/2006-02在南方医科大学南方医院动物研究所完成。选用健康中国版纳小型猪36只,按随机数字表法分为供、受体各18只,施行非转流小型猪原位肝移植手术18例。在非体外静脉转流的条件下行同种异体原位肝移植术,严格控制动物无肝期时间,应用套管法吻合胆总管,另外加强围手术期的处理,使无肝期的血压维持在满意水平。监测动物无肝期时间、手术时间、失血量、输血量及动物存活期;术中监测动物的血液动力学及动脉血气分析、生化指标变化;猪死后当天行尸体解剖明确死亡原因。结果:成功建立非转流小型猪原位肝移植模型18只,均纳入结果分析,无脱失。①实验动物无术中死亡,术后当天死亡1只,死亡原因为急性肺水肿;术后第2天死亡1只,死亡原因为胆总管吻合口胆瘘。术后7d存活率为88.9%。②手术时间、无肝期时间、术中失血量及输血量分别为(179.61±14.27)min,(27.28±3.43)min,(422.22±66.91)mL及(444.44±51.13)mL。③与无肝前期相比,实验动物无肝期平均动脉压、中心静脉压、pH值及碱剩余明显下降(P<0.05￣0.01),心率及血清钾水平显著升高(P<0.01);手术结束时平均动脉压及中心静脉压恢复,经药物调整后血清钾水平下降,pH值逐渐恢复。结论:非转流条件下的小型猪原位肝移植模型是肝移植实验的理想动物模型。