Abstract：
The purpose of this study was to investigate the effect of combined therapy of diacerein and gold nanoparticles (AuNP) on diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in a rat model. Normal healthy and DEN-induced (HCC) rats were divided into five groups. Group I healthy rats served as normal control, Group II untreated HCC rats, Group III HCC rats administered diacerein, Group IV HCC rats administered AuNP, and Group V HCC rats administered diacerein and AuNP. All treatments were given once daily for 4 weeks. Liver morphology and necroinflammation in all groups were evaluated using hematoxylin and eosin (H&E), Masson\'s trichrome for fibrosis, and immunohistochemistry assays for expression of TNF-α, IL-6, β-catenin, and caspase-3. Liver sections from Group II HCC rats showed loss of lobular architecture, thick fibrous tissue deposition, leukocyte infiltration, degenerated hepatocytes and HCC neoplastic nodules surrounded by extensive fibrosis. Group II had high expression of TNF-α, IL-6, and β-catenin, and low caspase-3 expression as compared to Group I. HCC rats treated with the combined therapy of diacerein and AuNP (Group V) showed markedly decreased HCC lesions, significant necroinflammation reduction (p ˂ 0.05) and 90% reduction in fibrosis as compared to Group II HCC + diacerein. This combined therapy also reduced (p ˂ 0.05) TNF-α, IL-6, β-catenin expression and increased caspase-3 expression. In conclusion, diacerein combined with AuNP synergistically attenuated the severity of HCC lesions by reducing necroinflammation and fibrosis, decreased TNF-α, IL-6, β-catenin expression, and increased caspase-3 expression for apoptosis.
摘要：
目的探讨双醋瑞因与纳米金（AuNP）联合治疗对二乙基亚硝胺（DEN）诱导的大鼠肝细胞癌（HCC）模型的影响。将正常健康和DEN诱导的（HCC）大鼠分为五组。Ⅰ组健康大鼠作为正常对照组,第二组未经治疗的肝癌大鼠，第三组肝癌大鼠服用双醋瑞因，IV组HCC大鼠给予AuNP，和第V组HCC大鼠施用双醋瑞因和AuNP。所有治疗每天给予一次,持续4周。使用苏木精和伊红（H&E）评估所有组的肝脏形态和坏死性炎症，Masson的纤维化三色，和免疫组织化学检测TNF-α的表达，IL-6，β-catenin，和caspase-3。来自II组HCC大鼠的肝脏切片显示小叶结构丧失，厚纤维组织沉积，白细胞浸润,变性肝细胞和肝癌肿瘤结节周围广泛的纤维化。Ⅱ组高表达TNF-α,IL-6和β-catenin，与I组相比，caspase-3表达低。用双醋瑞因和AuNP联合治疗的HCC大鼠（第V组）显示出明显减少的HCC病变，与II组HCC+双醋瑞因相比，坏死炎症显著减少(p=0.05)，纤维化减少90%。这种联合疗法也降低了(p=0.05)TNF-α，IL-6，β-catenin表达和caspase-3表达增加。总之,双醋瑞因联合AuNP通过减少坏死性炎症和纤维化协同减轻HCC病变的严重程度，降低TNF-α，IL-6，β-catenin表达，并增加caspase-3表达以促进细胞凋亡。
