Contribution of the toxic advanced glycation end-productsreceptor axis in nonalcoholic steatohepatitis-related hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most common malignancies worldwide. The main etiologies of HCC are hepatitis B virus and hepatitis C virus(HCV), and non-hepatitis B/non-hepatitis C HCC(NBNCHCC) has also been identified as an etiological factor. Although the incidence of HCV-related HCC in Japan has decreased slightly in recent years, that of NBNC-HCC has increased. The onset mechanism of NBNC-HCC, which has various etiologies, remains unclear; however, nonalcoholic steatohepatitis(NASH), a severe form of nonalcoholic fatty liver disease, is known to be an important risk factor for NBNC-HCC. Among the different advanced glycation end-products(AGEs) formed by the Maillard reaction, glyceraldehyde-derived AGEs, the predominant components of toxic AGEs(TAGE), have been associated with NASH and NBNC-HCC, including NASH-related HCC. Furthermore, the expression of the receptor for AGEs(RAGE) has been correlated with the malignant progression of HCC. Therefore, TAGE induce oxidative stress by binding with RAGE may, in turn, lead to adverse effects, such as fibrosis and malignant transformation, in hepatic stellate cells and tumor cells during NASH or NASH-related HCC progression. The aim of this review was to examine the contribution of the TAGE-RAGE axis in NASH-related HCC.

非酒精性脂肪性肝炎肝郁脾虚证大鼠模型的改进研究

目的:快速建立非酒精性脂肪性肝炎肝郁脾虚证的模型。方法:取40只SD大鼠,随机分为正常对照组(NC组)、高糖高脂饮食+生理盐水组(GTGZ+NS组)、高糖高脂饮食+10%CCl4组(GTGZ+10%CCl4组)、高糖高脂饮食+40%CCl4组(GTGZ+40%CCl4组)。NC组给予基础饲料进行常规喂养;其余3组给予高糖高脂饲料喂养并每日束缚3 h,于第7周开始分别给予3 mL/kg的0.9%生理盐水、10%CCl4油溶液、40%CCl4油溶液皮下注射,每周两次。第8周末,观察大鼠的一般行为学改变,检测血清转氨酶和血脂、海马组织5-羟色胺(5-HT)、去甲肾上腺素(NE)含量及尿D-木糖排泄率,进行肝脏HE、油红O和天狼星染色。结果:与NC组相比,各组大鼠血清转氨酶和血脂水平均明显升高(P﹤0.05),海马组织中的5-HT、NE以及尿D-木糖排泄率均降低(P﹤0.05),GTGZ+40%CCl4组大鼠的症状和体征更符合中医肝郁脾虚证的表现。结论:高糖高脂饮食加40%CCl4油溶液皮下注射结合束缚和饥饱失常的方法可快速建立非酒精性脂肪性肝炎肝郁脾虚证模型。