近日，國(guó)際知名《BioLogy Open》雜志在線發(fā)表了中國(guó)科學(xué)院昆明動(dòng)物研究所梁斌課題組題為“Tree shrew (Tupaia belangeri chinensis), a novel non-obese animal model of non-alcoholic fatty liver disease”的研究論文，研究報(bào)道稱(chēng)樹(shù)鼩是一種非肥胖型脂肪肝動(dòng)物模型。模型回答了樹(shù)鼩到底可以作為哪些人類(lèi)疾病模型。博士研究生張林強(qiáng)為第一作者，梁斌研究員為通訊作者。
非酒精性脂肪肝病目前正在逐漸成為一個(gè)嚴(yán)重的公共健康問(wèn)題，影響著大多數(shù)人的健康。隨著社會(huì)經(jīng)濟(jì)的快速發(fā)展，生活方式發(fā)生改變，大多數(shù)人處于高熱量食物攝入過(guò)多(營(yíng)養(yǎng)過(guò)剩)和長(zhǎng)時(shí)間久坐等狀態(tài)，加劇了非酒精性脂肪肝的流行。在歐美等發(fā)達(dá)國(guó)家，大約有20-30%的人患有非酒精性脂肪肝;在中國(guó)，有12-24%的人患有同樣的疾病。
臨床上，非酒精性脂肪肝患者常常伴有肥胖、高血糖、高血脂、胰島素抵抗甚至還有2型糖尿病等癥狀，對(duì)于這一類(lèi)非酒精性脂肪肝已經(jīng)有諸多的動(dòng)物模型來(lái)研究其發(fā)病機(jī)理。然而，在亞太地區(qū)，大約有15-40%，甚至更高的非酒精性脂肪肝患者卻并沒(méi)有表現(xiàn)出肥胖和糖尿病癥狀，遺憾的是，目前沒(méi)有合適的動(dòng)物模型來(lái)研究此類(lèi)非肥胖型非酒精性脂肪肝。
和常用的實(shí)驗(yàn)動(dòng)物大鼠和小鼠相比，樹(shù)鼩(Tupaia belangeri chinensis)在進(jìn)化上更加接近靈長(zhǎng)類(lèi)。然而，作為一種新型的實(shí)驗(yàn)動(dòng)物，我們不清楚，樹(shù)鼩到底可以作為哪些人類(lèi)疾病動(dòng)物模型。研究組前期開(kāi)展了樹(shù)鼩的體重、血糖、性別和年齡之間的研究，發(fā)現(xiàn)它們之間的關(guān)系和靈長(zhǎng)類(lèi)、人類(lèi)很類(lèi)似，提示樹(shù)鼩可以作為研究代謝性疾病的動(dòng)物模型(Relationships between body weight, fasting blood glucose concentration, sex and age in tree shrews (Tupaia belangeri chinensis)）。隨后，他們用高脂高膽固醇食物誘導(dǎo)的方法成功建立了樹(shù)鼩非酒精性脂肪肝動(dòng)物模型，該模型能夠模擬非酒精性脂肪肝的全部發(fā)病過(guò)程;比小鼠模型相比，其發(fā)病時(shí)間短，病癥顯著;并發(fā)現(xiàn)脂蛋白脂酶(LPL)在其發(fā)病過(guò)程中起著關(guān)鍵作用(Cholesterol induces lipoprotein lipase expression in a tree shrew (Tupaia belangeri chinensis) model of non-alcoholic fatty liver disease)。
然而，該模型的一個(gè)特點(diǎn)是不肥胖，由此帶來(lái)的科學(xué)問(wèn)題是，樹(shù)鼩是否是一種非肥胖型脂肪肝模型?因此，他們使用了4種不同的方法來(lái)處理樹(shù)鼩，每種方法包含有不同高熱量食物(如高糖、高脂、高膽固醇、高糖高脂組合)的組合。處理之后，各組樹(shù)鼩表現(xiàn)出不同程度的肝功能受損，同時(shí)伴隨有高血脂癥，但血糖并未呈現(xiàn)明顯變化。進(jìn)一步通過(guò)組織切片檢查其肝臟組織發(fā)現(xiàn)，所有樹(shù)鼩都出現(xiàn)肝臟脂肪積累，意味著都成功誘導(dǎo)了脂肪肝。但令人驚奇的是，和對(duì)照組樹(shù)鼩相比，這些脂肪肝樹(shù)鼩的體重并沒(méi)有增加，而且在皮下和腹腔等處也沒(méi)有脂肪組織的出現(xiàn)，說(shuō)明它們沒(méi)有出現(xiàn)肥胖，表明樹(shù)鼩是一種非肥胖型非酒精性脂肪肝動(dòng)物模型，但其發(fā)病機(jī)制有待未來(lái)繼續(xù)研究。 研究總結(jié)了樹(shù)鼩可以作為人類(lèi)非肥胖型脂肪肝模型，用來(lái)研究其發(fā)病機(jī)理和治療策略
原文鏈接：
Tree shrew (Tupaia belangeri chinensis), a novel non-obese animal model of non-alcoholic fatty liver disease
原文摘要：
Non-alcoholic fatty liver disease (NAFLD) is becoming a severe public health problem that is affecting a large proportion of the world population. Generally, NAFLD in patients is usually accompanied by obesity, hyperglycemia, insulin resistance (IR) and type 2 diabetes (T2D), for which numerous animal models have been generated in order to explore the pathogenesis and therapies of NAFLD. On the contrary, quite a number of NAFLD subjects, especially in Asian regions, are non-obese and non-diabetic; however, few animal models are available for the research of non-obese NAFLD. Here, four approaches (here called approach 1 to 4) corresponding to the variable compositions of diets were used to treat tree shrews (Tupaia belangeri chinensis), which have a closer evolutionary relationship to primates than rodents. Analysis of plasma biochemical parameters, hepatic histology, and the expression of hepatic lipid metabolic genes revealed that all four approaches led to hepatic lipid accumulation, liver injury and hypercholesterolemia, but had no effect on body weight and adipose tissue generation, or glycemia. Hepatic gene expression in tree shrews treated by approach 4 might suggest a different or non-canonical pathway leading to hepatic steatosis. In conclusion, the tree shrew displays hepatic steatosis and dyslipidemia, but remains non-obese and non-diabetic under high energy diets, which suggests that the tree shrew may be useful as a novel animal model for the research of human non-obese NAFLD.
