Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Nutrients. 2021 Dec 23;14(1):42. doi: 10.3390/nu14010042.
Non-alcoholic steatohepatitis (NASH) can cause liver cirrhosis and hepatocellular carcinoma (HCC), with cases increasing worldwide. To reduce the incidence of liver cirrhosis and HCC, NASH is targeted for the development of treatments, along with viral hepatitis and alcoholic hepatitis. Lactoferrin (LF) has antioxidant, anti-cancer, and anti-inflammatory activities. However, whether LF affects NASH and fibrosis remains unelucidated. We aimed to clarify the chemopreventive effect of LF on NASH progression. We used a NASH model with metabolic syndrome established using connexin 32 (Cx32) dominant negative transgenic (Cx32ΔTg) rats. Cx32ΔTg rats (7 weeks old) were fed a high-fat diet and intraperitoneally injected with dimethylnitrosamine (DMN). Rats were divided into three groups for LF treatment at 0, 100, or 500 mg/kg/day for 17 weeks. Lactoferrin significantly protected steatosis and lobular inflammation in Cx32ΔTg rat livers and attenuated bridging fibrosis or liver cirrhosis induced by DMN. By quantitative RT-PCR, LF significantly down-regulated inflammatory (, , , and ) and fibrosis-related (, , and ) cytokine mRNAs. Phosphorylated nuclear factor (NF)-κB protein decreased in response to LF, while phosphorylated JNK protein was unaffected. These results indicate that LF might act as a chemopreventive agent to prevent hepatic injury, inflammation, and fibrosis in NASH via NF-κB inactivation.
非酒精性脂肪性肝炎（NASH）可导致肝硬化和肝细胞癌（HCC），全球病例数不断增加。为了降低肝硬化和 HCC 的发病率，除了病毒性肝炎和酒精性肝炎外，NASH 也成为了治疗的目标。乳铁蛋白（LF）具有抗氧化、抗癌和抗炎作用。然而，LF 是否会影响 NASH 和纤维化仍不清楚。我们旨在阐明 LF 对 NASH 进展的化学预防作用。我们使用了一种代谢综合征的 NASH 模型，该模型是通过连接蛋白 32（Cx32）显性负转基因（Cx32ΔTg）大鼠建立的。Cx32ΔTg 大鼠（7 周龄）喂食高脂肪饮食，并腹腔内注射二甲基亚硝胺（DMN）。大鼠分为三组，分别用 LF 治疗 0、100 或 500mg/kg/天，共 17 周。LF 显著保护了 Cx32ΔTg 大鼠肝脏中的脂肪变性和小叶炎症，并减轻了 DMN 诱导的桥接纤维化或肝硬化。通过定量 RT-PCR，LF 显著下调了炎症（、、、和）和纤维化相关（、、和）细胞因子的 mRNA。LF 可使磷酸化核因子（NF）-κB 蛋白减少，而磷酸化 JNK 蛋白不受影响。这些结果表明，LF 可能通过 NF-κB 失活，作为一种化学预防剂，预防 NASH 中的肝损伤、炎症和纤维化。
