Gender and strain-specific differences in the development of steatosis in rats
Gender and strain-specific differences in the development of steatosis in rats
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DOI：
10.1177/0023677212473717
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发表时间：
2013-01
影响因子：
2.4
通讯作者：
S. Stöppeler;Daniel Palmes;M. Fehr;J. Hölzen;Andree Zibert;R. Siaj;H. Schmidt;H. Spiegel;R. Bahde
中科院分区：
文献类型：
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作者：
S. Stöppeler;Daniel Palmes;M. Fehr;J. Hölzen;Andree Zibert;R. Siaj;H. Schmidt;H. Spiegel;R. Bahde
非酒精性脂肪性肝病（NAFLD）是一种常见的问题，具有多种表型。虽然其发病机制尚未完全了解，但已确定了疾病进展的几个风险因素。因此，定义适当的动物模型可能有助于揭示NAFLD的发病机制。我们研究了刘易斯和Sprague-Dawley大鼠的两种性别（n = 6）喂养标准（标准）或高脂肪（HF）饮食三周。通过苏木精-伊红、Azan Heidenheim和油红染色评估疾病阶段，通过单链DNA（ssDNA）检测评估细胞凋亡，通过Ki-67染色评估肝再生。分析肝损伤和脂代谢（包括脂肪细胞因子）的血清标志物。喂食HF饲料的两种品系和性别的肝脏均表现出脂肪变性的证据。刘易斯大鼠出现微泡性脂肪变性，而Sprague-Dawley大鼠出现大泡性脂肪变性伴明显纤维化。两株乳腺癌中女性的脂肪变性程度较低，增殖率较高（P < 0.05）。性别特异性差异在HF饮食的刘易斯大鼠中最为显著，雌性大鼠的碱性磷酸酶、胆固醇、甘油三酯和瘦素水平低于雄性大鼠，低密度脂蛋白/高密度脂蛋白比值更有利（P < 0.05）。进行逆转录聚合酶链反应分析以证明对肝再生、纤维化和脂肪变性重要的各种基因表达的变化。HF饮食诱导的促血管生成基因如血管内皮生长因子受体1和2在雄性中下调（P < 0.05）在雌性中不存在。总之，菌株和性别在疾病进展中起主要作用。在设计研究时应考虑这些差异，并可能为推进治疗策略提供新的方法。
Non-alcoholic fatty liver disease (NAFLD) is a common problem with a wide variety of phenotypes. While its pathogenesis is still not fully understood, several risk factors for disease progression have been identified. Therefore, defining adequate animal models may serve to unreveal the pathogenesis in NAFLD. We studied Lewis and Sprague-Dawley rats of both genders (n = 6) fed standard (Std) or high-fat (HF) diet for three weeks. Disease stage was assessed by haematoxylin–eosin, Azan Heidenheim and Oil-Red staining, apoptosis by single-stranded DNA (ssDNA) detection and liver regeneration by Ki-67 staining. Serum markers of liver injury and lipid metabolism including adipocytokines were analysed. Livers of both strains and genders fed with HF diet demonstrated evidence of steatosis. Lewis rats developed microvesicular steatosis whereas Sprague-Dawley rats presented macrovesicular steatosis accompanied by pronounced fibrosis. Female gender of both strains was associated with lower steatosis grade and higher proliferation rate (P < 0.05). Gender-specific differences were most prominent in Lewis rats on a HF diet, where females showed lower alkaline phosphatase, cholesterol, triglyceride and leptin levels and a more favourable low-density lipoprotein/high-density lipoprotein ratio than males (P < 0.05). Reverse transcriptase-polymerase chain reaction analysis was performed to demonstrate changes in expression of various genes important for liver regeneration, fibrosis and steatosis. HF diet induced downregulation of proangiogenic genes such as vascular endothelial growth factor receptor 1 and 2 (P < 0.05) in males was not present in females. In conclusion, strain and gender served major roles in disease progression. These differences should be considered when designing studies and may offer new ways to advance therapeutic strategies.