盐酸小檗碱缓解高胆固醇所致肝脏损伤的机制体外及动物实验研究

Animal and in vitro study on mechanism of berberine alleviating high cholesterol induced liver injury

Objective: To investigate the protective effect of berberine (BBR) on liver damage under high-cholesterol diet challenge. Methods: Eight-week old male C57BL/6J mice were randomly divided into normal diet group, high cholesterol diet (1.25% cholesterol+0.5% cholic acid) group and high cholesterol diet+BBR (100 mg/kg per day by gavage) group, with 10 mice in each group. Liver and serum plasma samples were collected after 8-week feeding. Hepatic mRNA expressions of genes involved in endoplasmic reticulum stress (ER stress), oxidative stress and inflammatory cytokines were determined by real-time quantitative PCR, and content of malondialdehyde (MDA) in liver tissues was measured. HepG₂ cell line was used to investigate the effect of BBR on ER stress under high cholesterol challenge. Results: Compared with normal diet group, hepatic mRNA expressions of genes in ER stress, oxidative stress and inflammatory cytokines increased significantly in high cholesterol diet group (P<0.05), and were reduced closely to levels of normal diet group by BBR treatment (P<0.05). BBR also down-regulated the increased hepatic MDA content induced by high cholesterol diet (P<0.05). Furthermore, BBR decreased the expression of GRP78, a key protein marker concerning ER stress (P<0.05), as well as the fluorescence intensity of DHE probe after high cholesterol treatment in HepG₂ cells. Conclusions: BBR could effectively ameliorate hepatic ER stress, oxidative stress and inflammatory response under high cholesterol challenge, which might protect liver from damage when overloaded with cholesterol.