An evaluation of the marmoset Callithrix jacchus (sagüi) as an experimental model for the dyslipoproteinemia of human Schistosomiasis mansoni

Vera L.M. Lima , Vera L.M. Sena , Bruce Stewart , James S. Owen , Peter J. Dolphin
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引用次数: 18

Abstract

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.

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作为人类曼氏血吸虫病异常脂蛋白血症实验模型的狐猴贾克斯狐猴(sag i)的评价
人感染曼氏血吸虫在南美地区相对常见,并与肝功能障碍和脂蛋白异常血症有关。具体表现为血浆卵磷脂活性:胆固醇酰基转移酶(LCAT)活性降低,血浆胆固醇酯浓度下降,磷脂浓度升高,红细胞膜胆固醇富集。以往的研究利用啮齿类动物(大鼠和小鼠)作为实验模型来研究曼氏梭菌感染引起的脂蛋白异常血症。然而,这些动物的血浆脂蛋白谱与人类非常不同,感染并不伴随着LCAT活性降低或红细胞膜胆固醇富集。在这里,我们评估了狨猴Callithrix jacchus (sag i)的适用性,这种狨猴体型小,在巴西很容易获得,作为研究曼氏沙门氏菌感染的脂蛋白异常血症的潜在动物模型。与大鼠或小鼠不同,sag i的血浆脂蛋白组成和分布近似于人类,LDL代表了主要的脂蛋白种类。在sag i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,而大鼠和小鼠的分子种类倾向于长链更不饱和的种类。像啮齿类动物一样,sag i可以成功感染曼氏链球菌,60天后,这导致血浆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以前报告的人类感染后的变化非常相似。基于这些变化,并观察到sag i与人类的血浆脂蛋白谱相似,我们得出结论,雅库斯贾库斯(sag i)是研究与mansoni感染相关的脂蛋白异常血症的合适动物模型。
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