Establishment of a Spontaneous Liver Fibrosis Model in NOD/SCID Mice Induced by Natural Aging.
Establishment of a Spontaneous Liver Fibrosis Model in NOD/SCID Mice Induced by Natural Aging.
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肝纤维化是一种慢性疾病，可导致严重的健康问题，包括肝癌。然而，自然衰老引起的肝纤维化的发病机制尚未完全清楚。对于研究肝纤维化的研究人员来说，进行机制研究和测试抗肝纤维化疗法的重要工具是能够反映肝纤维化病理原因的体内模型。本研究旨在建立自然衰老诱导的NOD/SCID小鼠自发性肝纤维化模型。使用最先进的纤维化相关测量证实了该模型的有效性。该研究为进一步研究肝纤维化的病因和潜在的治疗方法提供了有用的工具。这些发现可能有助于开发慢性肝病的新疗法，这些慢性肝病影响着全球数百万人。肝纤维化是慢性肝病的重要病理特征，由多种致病因素引起。因此，建立合适的动物模型来模拟肝纤维化对了解其发病机制具有重要意义。尽管有许多方法可用于生成肝纤维化模型，但它们通常基本上偏离自发的年龄相关性肝纤维化过程。在本研究中，与青年（12周）和中年（32周）NOD/SCID小鼠相比，老年NOD/SCID小鼠（43周，43 W）肝组织中有大量的纤维间隔和胶原。免疫组织化学分析明确表明43 W小鼠肝组织中α-SMA含量升高，从而强调了衰老在触发上皮向间质转化中的作用。此外，43 W小鼠的SA-β-gal染色和P21表达增加，SIRT 1和SIRT 3表达减少。一个全面的评价，包括透射电子显微镜和荧光定量分析阐明受损的线粒体功能和降低抗氧化能力的43 W小鼠的肝细胞。此外，衰老过程激活了促纤维化TGF-β-SMAD通路，同时诱导肝细胞炎症。本研究的结果不仅验证了通过自然衰老诱导的自发性肝纤维化小鼠模型的成功构建，而且还为年龄诱导的肝纤维化的机制提供了初步见解。
Liver fibrosis is a chronic disease that can lead to serious health problems, including liver cancer. However, the pathogenesis of liver fibrosis caused by natural aging is not fully understood. For researchers studying liver fibrosis, an important tool for conducting mechanism research and testing anti-liver fibrosis therapies is an in vivo model that can reflect the pathological causes of liver fibrosis. This study aimed to establish a model of spontaneous liver fibrosis in NOD/SCID mice induced by natural aging. This model’s validity was confirmed using cutting-edge fibrosis-related measurements. This study provides a useful tool for further research into the causes and potential treatments for liver fibrosis. The findings may help to develop new therapies for chronic liver diseases which affect millions of people worldwide. Liver fibrosis, a critical pathological feature of chronic liver diseases, arises from a multitude of pathogenic factors. Consequently, establishing an appropriate animal model to simulate liver fibrosis holds immense significance for comprehending its underlying pathogenesis. Despite the numerous methodologies available for generating liver fibrosis models, they often deviate substantially from the spontaneous age-related liver fibrosis process. In this study, compared with young (12 weeks) and middle-aged NOD/SCID mice (32 weeks), there were a large number of fibrous septum and collagen in the liver tissue of old NOD/SCID mice (43 weeks, 43 W). Immunohistochemical analysis unequivocally indicated heightened α-SMA content within the liver tissue of the 43 W mice, thereby underscoring aging’s role in triggering the epithelial-to-mesenchymal transition. In addition, SA-β-gal staining as well as P21 expression were increased, and SIRT1 and SIRT3 expression were decreased in 43 W mice. A comprehensive evaluation encompassing transmission electron microscopy and fluorescence quantitative analysis elucidated compromised mitochondrial function and reduced antioxidant capacity in hepatocytes of the 43 W mice. Furthermore, the aging process activated the pro-fibrotic TGF-β-SMAD pathway, concurrently inducing hepatocellular inflammation. The results of the present study not only validate the successful construction of a spontaneous liver fibrosis mouse model through natural aging induction but also provide initial insights into the mechanisms underpinning age-induced liver fibrosis.
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影响因子：
64.5
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11.4
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5.3
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