【摘要】 目的研究广枣提取物(CAE)干预对酒精性肝病大鼠血脂代谢、肝细胞凋亡及内质网应激(ERS)相关蛋白表达的影响。方法将60只雄性Wistar大鼠随机分为正常对照组(A组)、模型组(B组)、CAE低剂量组(C组)、CAE中剂量组(D组)、CAE高剂量组(E组)和阳性对照组(F组,益肝灵片),每组各10只。采用梯度浓度酒精、分次少量灌胃的方法建立大鼠慢性酒精性肝病模型,同时给予CAE保护。干预8周后测定各组的三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、游离脂肪酸(FFA)水平,观察各组的肝细胞GRP78/Caspase3比值及凋亡情况。结果 B、C、D、E、F组的TG、TC、LDL-C、FFA水平均高于A组,B、C、D、E组的HDL-C水平均低于A组,差异有统计学意义(P<0.01或P<0.05);F组与A组的HDL-C水平比较,差异无统计学意义(P>0.05);C、D、E、F组的TG、TC、FFA、LDL-C水平均低于B组,D、E、F组的HDL-C水平均高于B组,差异有统计学意义(P<0.01);C组与B组的HDL-C水平比较,差异无统计学意义(P>0.05)。B组的肝细胞凋亡率显著高于A组,差异有统计学意义(P<0.01);C、D、E组的肝细胞凋亡率均显著低于B组,差异有统计学意义(P<0.01)。B组的肝细胞GRP78/Caspase3比值显著低于A组,差异有统计学意义(P<0.01);D、E组的肝细胞GRP78/Caspase3比值均显著高于B组,差异有统计学意义(P<0.01);C组的肝细胞GRP78/Caspase3比值高于B组,但差异无统计学意义(P>0.05)。HE染色显示CAE能明显改善大鼠肝脏组织病变范围与程度,使炎性细胞浸润减少。结论 CAE保肝功效可能与其抗氧化活性和阻制ERS诱导的肝细胞凋亡有关。更多还原

【Abstract】 Objective To investigate the effect of Choerospondias Axillaries extracts(CAE) intervention on blood lipid metabolism, hepatocyte apoptosis and endoplasmic reticulum stress(ERS)-related protein expression in rats with alcoholic liver disease. Methods Sixty male Wistar rats were randomly divided into normal control group(group A), model group(group B), CAE low dose group(group C), CAE middle dose group(group D), CAE high dose group(group E) and positive control group(group F, Yiganling Tablets), 10 rats in each group. After 8 weeks of intervention, the levels of triglyceride(TG), total cholesterol(TC), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C), and free fatty acid(FFA) were determined. The ratio of GRP78/Caspase3 and apoptosis in hepatocytes were observed. Results The levels of TG, TC, LDL-C and FFA in group B, C, D, E and F were higher than those in group A, and the levels of HDL-C in group B, C, D and E were lower than those in group A, with statistically significant differences(P<0.01 or P<0.05). There was no significant difference in HDL-C level between group F and group A(P>0.05). The levels of TG, TC, FFA and LDL-C in group C, D, E and F were lower than those in group B, the HDL-C levels in group D, E and F were higher than those in group B, and the differences were statistically significant(P<0.01). There was no significant difference in HDL-C level between group C and group B(P>0.05). The apoptosis rate of hepatocytes in group B was significantly higher than that in group A, and the difference was statistically significant(P<0.01). The apoptotic rate of hepatocytes in group C, D and E was significantly lower than that in group B, and the differences were statistically significant(P<0.01). The ratio of GRP78/Caspase3 of hepatocytes in group B was significantly lower than that in group A, and the difference was statistically significant(P <0.01). The ratio of GRP78/Caspase3 of hepatocytes in group D and E was significantly higher than that in group B, and the difference was statistically significant(P<0.01). The ratio of GRP78/Caspase3 of hepatocytes in group C was higher than that in group B, but the difference was not statistically significant(P>0.05). HE staining showed that CAE could significantly improve the range and extent of liver tissue lesions in rats, and reduce inflammatory cell infiltration. Conclusion The liver-protecting effect of CAE may be related to its antioxidant activity and inhibition of ERS-induced hepatocyte apoptosis.更多还原