【摘要】 旨在探讨高脂饮食诱导的肥胖与常见霉菌毒素黄曲霉毒素B1(aflatoxin B1,AFB1)联合作用对肝脏氧化应激及炎症反应的影响机制。将36只体质量相近的4周龄SD大鼠随机分成4组，每组9只，分别为：空白对照组(基础日粮)、AFB1组(0.4 mg/kg AFB1+基础日粮)、HFD组(高脂日粮)、HFD+AFB1组(高脂日粮+0.4 mg/kg AFB1)。通过苏木精-伊红(HE)染色和油红O染色观察组织病理学变化及脂肪沉积情况；通过试剂盒检测氧化应激因子和炎症相关因子的含量；并利用Western blot检测Nrf2-Keap1信号通路相关因子的蛋白相对表达水平。HE染色结果显示，AFB1组肝细胞广泛性水样变性，细胞核萎缩破裂，炎症细胞浸润，成纤维组织增生。HFD组出现肝细胞脂肪变性，胞浆出现脂滴浸润，门管区可见肝纤维化，纤维化区域肝细胞坏死，并伴随炎症细胞浸润，出现脂褐素颗粒。而HFD作用于AFB1组时，肝脏组织间质及间隙异常的状态进一步加剧，出现了大量的脂滴。油红O染色结果显示，HFD组的肝组织可见大量颜色较深的红色脂滴，呈条索状融合。AFB1组大鼠的肝组织内也能观察到红色脂滴，但数量和程度都明显少于HFD组。HFD+AFB1组大鼠的肝组织红色脂滴的数量和程度都分别高于AFB1组和HFD组；HFD通过升高ROS、MDA水平和降低抗氧化应激因子CAT、SOD、Nrf2、HO-1、NQO1、GCLC的表达加重了AFB1诱导的氧化应激。此外，HFD与AFB1的联合作用进一步显著提升了体内炎症因子IL-2、IL-6、TNF-α、IL-1β水平。综上所述，HFD处理通过Nrf2-keap1信号通路显著加剧了AFB1诱导的大鼠肝脏氧化应激和炎症反应。更多还原

【Abstract】 This study aims to investigate the mechanisms underlying the effects of the combined action of high-fat diet-induced obesity and the aflatoxin B1(AFB1) on hepatic oxidative stress and inflammatory responses,Thirty-six rats of similar weight and 4 weeks old were randomly divided into 4 groups,with 9 rats in each group:the blank control group(basal diet),the AFB1 group(0.4 mg/kg AFB1+basal diet),the HFD group(high-fat diet),and the HFD+AFB1 group(highfat diet+0.4 mg/kg AFB1).Histological changes and lipid deposition were observed via hematoxylin-eosin(HE) staining and Oil Red O staining.Levels of oxidative stress and inflammation-related factors were measured using commercial assay kits,The relative protein expression levels of factors involved in the Nrf2-Keapl signaling pathway were assessed by Western blot analysis.The HE staining results showed that in the AFB1 group,the liver cells exhibited widespread watery degeneration,with shrunk and ruptured nuclei,inflammatory cells infiltration,and increased fibrosis.In the HFD group,liver cell fatty degeneration was observed,with cytoplasmic lipid droplet infiltration.In the portal area,liver fibrosis was seen,with liver cell necrosis and inflammatory cell infiltration in the fibrotic area,accompanied by lipofuscous granules.When HFD was applied to the AFB1 group,the abnormal state of liver interstitial and interstitial spaces was further aggravated,and a large number of lipid droplets appeared.The Oil Red O staining results showed that there were large numbers of dark red lipid droplets in the liver tissue of the HFD group,which were fused in strands.In the AFB1 group,lipid droplets could also be observed in the liver tissue of rats,but the number and degree were significantly less than those in the HFD group.The number and degree of red lipid droplets in the liver tissue of rats in the HFD+AFB1 group were higher than those in the AFB1 group and the HFD group.HFD exacerbated AFB1-induced oxidative stress by elevating ROS,MDA levels,and decreasing the expression of antioxidant stress factors such as CAT,SOD,Nrf2,HO-1,NQO1,and GCLC.Furthermore,the combined effect of HFD and AFB1further significantly increased the levels of pro-inflammatory cytokines IL-2,IL-6,TNF-α,and IL-1β in the body.In summary,HFD treatment significantly exacerbated liver oxidative stress and inflammatory responses in rats exposed to AFB1 through the Nrf2-keapl signaling pathway.更多还原