促红细胞生成素（EPO）被认为在红细胞生成中具有功能，然而其对肝纤维化的潜在抗纤维化效果尚不清楚。本研究检测了EPO是否会影响硫代乙酰胺（TAA）引起的肝纤维化，重点关注Toll样受体4（TLR4）级联和磷脂酰肌醇3-激酶（PI3K）/Akt通路作为可能的途径。雄性Wistar大鼠随机分为四组，包括：阴性对照组、TAA组（腹腔注射；每周三次，TAA 100 mg/kg，连续2周）和EPO处理组（150 和 300 IU/kg，腹腔注射），在TAA注射后连续2周。EPO剂量依赖性地减轻了肝纤维化，表现为血清丙氨酸转氨酶和天冬氨酸转氨酶活性降低，白蛋白水平增加。EPO抑制了组织中肿瘤坏死因子-α、白细胞介素-1β、转化生长因子-β1和TLR4的水平增加，提高了PI3K和p-PI3K的水平。EPO的抗氧化性质通过恢复肝谷胱甘肽和超氧化物歧化酶，防止肝马来醛的积累而得到证明。此外，EPO增加了PI3K和Akt的蛋白表达，降低了TLR4的蛋白表达。免疫组化结果显示，EPO处理改变了组织组织学，下调了丝裂原活化蛋白激酶蛋白的表达。总之，研究表明EPO可以通过上调PI3K/Akt信号级联和下调TLR4下游轴来预防TAA引起的肝纤维化。

Erythropoietin (EPO) is recognized for its function in erythropoiesis; however, its potential antifibrotic effect against liver fibrosis remains unknown. This study examined whether EPO affects thioacetamide (TAA)-induced liver fibrosis by concentrating on the Toll-like receptor 4 (TLR4) cascade and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway as possible pathways. Male Wistar rats were randomized into four groups, which included: the negative control group, the TAA group (intraperitoneal; TAA 100 mg/kg three times per week for 2 weeks), and EPO-treated groups (150 and 300 IU/kg, i.p.) for 2 weeks after TAA injections. EPO attenuated hepatic fibrosis in a dosage-dependent way, as manifested by the diminution in serum alanine aminotransferase and aspartate aminotransferase activities, as well as the increase in albumin level. EPO inhibited the increase in tissue levels of tumor necrosis factors-α, interleukin-1β, transforming growth factor-β1, and TLR4 and raised tissue levels of PI3K and p-PI3K. EPO antioxidant properties were demonstrated by restoring hepatic glutathione and superoxide dismutase by preventing the accumulation of hepatic malondialdehyde. Further, EPO increased the protein expression of PI3K and Akt and decreased TLR4 protein expression. Immunohistochemically, EPO treatment altered tissue histology and downregulated mitogen-activated protein kinase protein expression. Overall, the research suggested that EPO could prevent TAA-induced hepatic fibrosis through upregulating the PI3K/Akt signaling cascade and downregulation the TLR4 downstream axis.Copyright © 2023 Marawan A. Elbaset et al.