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AJPGLP:动物模型帮助科学家理解脂肪肝的发病机制

  1. AJPGLP
  2. 动物模型
  3. 发病机制
  4. 理解
  5. 脂肪肝

来源:生物谷 2012-11-18 11:28

近日,来自德克萨斯州的科学家们开发出了一种实验室的负鼠(opossum)可以作为新型的动物模型来研究常见的肝脏疾病。非酒精性脂肪性肝炎(NASH)类似于酒精性肝病,但是常常高发于那些不饮酒或者饮酒很少的人身上。NASH的主要特征是肝脏中脂肪的积累,而且和炎症、功能性的肝损伤伴生。

近日,来自德克萨斯州的科学家们开发出了一种实验室的负鼠(opossum)可以作为新型的动物模型来研究常见的肝脏疾病。非酒精性脂肪性肝炎(NASH)类似于酒精性肝病,但是常常高发于那些不饮酒或者饮酒很少的人身上。NASH的主要特征是肝脏中脂肪的积累,而且和炎症、功能性的肝损伤伴生。

NASH影响着2%-5%的美国人的健康,而且另有15%-30%的美国人肝脏中存在过多的脂肪,但是没有炎症和肝损伤,这种病症成为脂肪肝或者非酒精性脂肪肝(NAFLD)。研究者的相关研究成果刊登在了近日的国际杂志Physiology-Gastrointestinal and Liver Physiology上。

这项新的研究中,当喂食高胆固醇和高脂肪食物时候,高反应的负鼠可以产生高水平的胆固醇以及脂肪肝疾病,低反应的负鼠并不会产生这种效应。高应答个体会携带ABCB4基因的突变,这会影响其将肝脏过多胆固醇分泌成为胆汁的能力,反过来,这种个体会将胆固醇通过排泄运输至肠组织。因此携带有基因突变的负鼠会在肝脏中积累胆固醇,最终胆固醇水平会在血液中体现。

研究者Jeannie表示,高效应个体的脂肪肝包含了大量的胆固醇,负鼠将成为一种新的动物模型来研究胆固醇介导肝损伤的途径和机制,这将使得我们更好地理解NASH的发病机制。(生物谷Bioon.com)

编译自:New Animal Model May Lead to Treatments for Common Liver Disease

Steatohepatitis in laboratory opossums exhibiting a high lipemic response to dietary cholesterol and fat

Jeannie Chan1,2, Francis E. Sharkey3, Rampratap S. Kushwaha1, Jane F. VandeBerg1,2, and John L. VandeBerg1,2 .

Plasma VLDL and LDL cholesterol were markedly elevated (>40-fold) in high-responding opossums, but moderately elevated (6-fold) in low-responding opossums after they had consumed a high-cholesterol and high-fat diet for 24 wk. In both high- and low-responding opossums, plasma triglycerides were slightly elevated, threefold and twofold, respectively. Dietary challenge also induced fatty livers in high responders, but not in low responders. We studied the lipid composition, histopathological features, and gene expression patterns of the fatty livers. Free cholesterol (2-fold), esterified cholesterol (11-fold), and triglycerides (2-fold) were higher in the livers of high responders than those in low responders, whereas free fatty acid levels were similar. The fatty livers of high responders showed extensive lobular disarray by histology. Inflammatory cells and ballooned hepatocytes were also present, as were perisinusoidal fibrosis and ductular proliferation. In contrast, liver histology was normal in low responders. Hepatic gene expression revealed differences associated with the development of steatohepatitis in high responders. The accumulation of hepatic cholesterol was concomitant with upregulation of the HMGCR gene and downregulation of the CYP27A1, ABCG8, and ABCB4 genes. Genes involved in inflammation (TNF, NFKB1, and COX2) and in oxidative stress (CYBA and NCF1) were upregulated. Upregulation of the growth factor genes (PDGF and TGFB1) and collagen genes (Col1A1, Col3A1, and Col4A1) was consistent with fibrosis. Some of the histological characteristics of the fatty livers of high-responding opossums imitate those in the livers of humans with nonalcoholic steatohepatitis.

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