目的 探討大黃酚對慢性乙型病毒性肝炎（CHB）大鼠肝功能損傷及肝臟纖維化的影響，并分析相關作用機制。方法 60只雄性SD大鼠隨機分為對照組、模型組及大黃酚低、高劑量（7.5、30 mg/kg）組和拉米夫定（10 mg/kg）組，每組12只。除對照組外，其余各組均尾iv乙型肝炎病毒（HBV）抗原構建CHB模型，造模成功后個給藥組ip相應藥物。采用全自動生化分析儀檢測大鼠血清中天冬氨酸氨基轉移酶（AST）、丙氨酸氨基轉移酶（ALT）、總膽紅素（TBIL）水平；酶聯(lián)免疫吸附（ELISA）法檢測大鼠血清中透明質酸（HA）、層黏連蛋白（LN）、羥脯氨酸（HYP）水平；蘇木精–伊紅（HE）染色及Masson染色觀察大鼠肝臟組織病理形態(tài)學及纖維化；Western blotting法檢測大鼠肝臟組織中相關蛋白表達。結果 與模型組比較，大黃酚7.5、30 mg/kg組和拉米夫定組大鼠血清中ALT、AST、TBIL、HA、LN、HYP水平均降低（P＜0.05），大鼠肝組織病理性損傷和膠原纖維沉積顯著改善，肝組織中α-平滑肌肌動蛋白（α-SMA）、I型膠原α1基因（COL1A1）、葡萄糖調節(jié)蛋白（GRP）78、GRP94及磷酸化真核生物翻譯起始因子2α（p-eIF2α）/eIF2α、磷酸化蛋白激酶R樣內質網(wǎng)激酶（p-PERK）/PERK均顯著降低（P＜0.05）；且大黃酚30 mg/kg組、拉米夫定組大鼠血清和肝組織中上述指標均顯著優(yōu)于大黃酚7.5 mg/kg組（P＜0.05）。結論 大黃酚可能通過調控內質網(wǎng)應激減輕CHB大鼠肝功能損傷，改善大鼠肝纖維化。

Objective To investigate the effects of chrysophanol on liver function injury and liver fibrosis in rats with chronic viral hepatitis B (CHB),and to analyze the related mechanism.Methods Sixty male SD rats were randomly divided into control group,model group,chrysophanol low-dose and high-dose (7.5 and 30 mg/kg) groups,and lamivudine (10 mg/kg) group,with 12 rats in each group.Except for the control group,the CHB model was constructed by iv hepatitis B virus (HBV) antigen in the tail of the other groups,and the corresponding drugs were ip after successful modeling.The serum levels of AST,ALT,and TBIL were detected by automatic biochemical analyzer.The levels of HA,LN,and HYP in serum were detected by ELISA method.HE staining and Masson staining were used to observe the pathological morphology and fibrosis of liver tissue.The expression of related proteins in rat liver was detected by Western blotting.Results Compared with model group,the levels of ALT,AST,TBIL,HA,LN,and HYP in serum of rats in rheophanol 7.5,30 mg/kg groups and lamivudine groups were decreased (P<0.05),and pathological injury and collagen fiber deposition in liver tissue of rats were significantly improved.The levels of α-SMA,COL1A1,GRP78,GRP94,p-EIF2α/EIF2α,p-PERK/PERK ratio in liver tissue were significantly decreased (P<0.05).The above indexes in serum and liver tissue of rats in chrysophanol 30 mg/kg group and lamivudine group were significantly better than those in chrysophanol 7.5 mg/kg group (P<0.05).Conclusion Chrysophanol may reduce liver function injury and improve liver fibrosis in rats with CHB by regulating endoplasmic reticulum stress.

R285.5

新疆維吾爾自治區(qū)自然科學基金資助項目(2021D01C216)