本研究旨在评估雌激素和雌激素受体对二乙基亚硝胺（DEN）诱导的大鼠肝细胞癌（HCC）的潜在保护作用。单独接受 DEN 的卵巢切除 (OVX) 大鼠和 SHAM 大鼠的肝损伤血清生物标志物水平、肝脏白细胞介素 6 (IL-6) 含量、相对肝脏重量和肝脏组织学图像失真均显着升高，且当接受 DEN 治疗时进一步升高。与非 DEN 治疗的大鼠相比，DEN 联合氟维司群 (F)。 OVX 大鼠比 SHAM 大鼠表现出更高的损伤。在接受苯甲酸雌二醇 (EB)、水飞蓟素 (S) 或奥利司他 (ORS) 的 OVX 大鼠中，这些参数的逐渐减少的影响很明显。肝组织的免疫组织化学和/或蛋白质印迹分析显示，与SHAM大鼠相比，接受DEN和/或F的OVX和SHAM大鼠的脂肪酸合酶（FASN）和分化簇36（CD36）表达显着增加。与S相反，用EB治疗OVX大鼠可减轻DEN诱导的肝组织中FASN和CD36的表达，而ORS则改善DEN诱导的FASN表达。总之，对 HCC 的保护作用是通过雌激素受体 α (ER-α) 介导的，雌激素受体 α 消除了参与脂质代谢的下游基因，即 FASN 和 CD36，从而剥夺了肿瘤生存的重要能量来源。此外，ORS 对 DEN 诱导的 HCC 具有类似的缓解作用，这可能归因于 FASN 抑制和抗炎作用。此外，S 还可以减轻 DEN 诱发的 HCC，而与雌激素作用无关。

This study was designed to evaluate the potential protective impact of estrogen and estrogen receptor against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. The levels of liver injury serum biomarkers, liver content of interleukin-6 (IL-6), relative liver weight and distortion of liver histological pictures were significantly increased in ovariectomized (OVX) rats and SHAM rats that received DEN alone and were further exaggerated when DEN was combined with fulvestrant (F) compared to non-DEN treated rats. The OVX rats showed higher insults than SHAM rats. The tapering impact on these parameters was clear in OVX rats that received estradiol benzoate (EB), silymarin (S) or orlistat (ORS). The immunohistochemistry and/or Western blot analysis of liver tissues showed a prominent increase in fatty acid synthase (FASN) and cluster of differentiation 36 (CD36) expressions in OVX and SHAM rats who received DEN and/ or F compared to SHAM rats. In contrast to S, treatment of OVX rats with EB mitigated DEN-induced expression of FASN and CD36 in liver tissue, while ORS improved DEN-induced expression of FASN. In conclusion, the protective effect against HCC was mediated via estrogen receptor alpha (ER-α) which abrogates its downstream genes involved in lipid metabolism namely FASN and CD36 depriving the tumor from survival vital energy source. In addition, ORS induced similar mitigating effect against DEN-induced HCC which could be attributed to FASN inhibition and anti-inflammatory effect. Furthermore, S alleviated DEN-induced HCC, independent of its estrogenic effect.