Lima V L, Sena V L, Stewart B, Owen J S, Dolphin P J
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Brazil.
Biochim Biophys Acta. 1998 Aug 28;1393(2-3):235-43. doi: 10.1016/s0005-2760(98)00076-9.
Human infection with the parasite Schistosoma mansoni is a relatively common occurrence in regions of South America and is associated with liver dysfunction and dyslipoproteinemia. Specifically, the activity of plasma lecithin:cholesterol acyltransferase (LCAT) activity is reduced, the concentration of plasma cholesterol esters falls, phospholipid concentrations are elevated and erythrocyte membranes become cholesterol enriched. Previous studies have utilized rodents (rats and mice) as experimental models to study the dyslipoproteinemia induced by S. mansoni infection. However, the plasma lipoprotein profiles in these animals is very different from humans and infection is not accompanied by decreases in LCAT activity or cholesterol enrichment of their erythrocyte membranes. Here we have evaluated the suitability of the marmoset Callithrix jacchus (sagüi) which is small and readily available in Brazil, as a potential animal model for the study of the dyslipoproteinemia of S. mansoni infections. The plasma lipoprotein compositions and distributions in sagüi, unlike rats or mice, approximate those of man with the LDL representing a major lipoprotein species. The molecular species of phospholipids, cholesterol esters and triglycerides present in sagüi plasma are also very similar to man, whereas those of rats and mice favor the longer chain more unsaturated species, Sagüi, like rodents, can be successfully infected with S. mansoni and after 60 days, this results in a 50% reduction in plasma LCAT activity, an 11% reduction in plasma cholesterol esters, an absolute increase of 46% in plasma phospholipids and an 18% increase in the cholesterol content of erythrocyte membranes. These changes are qualitatively and quantitatively very similar to those previously reported following human infections. Based upon these changes, and the observation that the plasma lipoprotein profile of sagüi and human is similar, we conclude that C. jacchus (sagüi) is an appropriate animal model for the study of dyslipoproteinemia associated with S. mansoni infections.
人体感染曼氏血吸虫在南美洲地区较为常见,且与肝功能障碍和血脂蛋白异常有关。具体而言,血浆卵磷脂:胆固醇酰基转移酶(LCAT)的活性降低,血浆胆固醇酯浓度下降,磷脂浓度升高,红细胞膜胆固醇含量增加。以往的研究利用啮齿动物(大鼠和小鼠)作为实验模型来研究曼氏血吸虫感染诱发的血脂蛋白异常。然而,这些动物的血浆脂蛋白谱与人类有很大差异,感染时其LCAT活性不会降低,红细胞膜也不会出现胆固醇富集现象。在此,我们评估了狨猴(Callithrix jacchus,即普通狨)作为研究曼氏血吸虫感染所致血脂蛋白异常潜在动物模型的适用性。普通狨的血浆脂蛋白组成和分布与大鼠或小鼠不同,与人类相近,低密度脂蛋白(LDL)是主要的脂蛋白种类。普通狨血浆中存在的磷脂、胆固醇酯和甘油三酯的分子种类也与人类非常相似,而大鼠和小鼠则倾向于更长链、更不饱和的种类。普通狨与啮齿动物一样,能够成功感染曼氏血吸虫,60天后,会导致血浆LCAT活性降低50%,血浆胆固醇酯降低11%,血浆磷脂绝对增加46%,红细胞膜胆固醇含量增加18%。这些变化在质量和数量上与先前报道的人类感染后的变化非常相似。基于这些变化以及普通狨与人类血浆脂蛋白谱相似的观察结果,我们得出结论,普通狨是研究与曼氏血吸虫感染相关的血脂蛋白异常的合适动物模型。