紫苏叶总黄酮对APAP诱导的急性肝损伤的保护作用OA北大核心CSTPCD
Protective Effect of Total Favonoids of Perilla frutescens on APAP-Induced Acute Liver Injury
目的:本文主要研究紫苏叶总黄酮(Perilla flavone,PF)纯化的最佳方法,以及其对对乙酰氦基酚(Paracetamol,APAP)诱导的急性肝损伤的保护作用及可能的作用机制.方法:采用单因素实验确定大孔树脂纯化紫苏叶总黄酮的最佳条件.将BALB/c雄性小鼠随机分为6组,空白对照组(CON)、模型组(MOD)、联苯双酯组(DDB)、PF 低剂量组(L-PF,12.5 mg/kg)、PF 中剂量组(M-PF,25 mg/kg)、PF 高剂量组(H-PF,50 mg/kg),连续灌胃给药15 d.末次给药1h后,除CON组外,每组腹腔注射APAP建立肝损伤模型.测定小鼠血清中谷草转氦酶(AST)、谷丙转氦酶(ALT)水平;测定小鼠肝脏中丙二醛(MDA)、超氧化物歧物酶(SOD)、还原型谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-PX)的水平;对小鼠肝脏进行HE染色观察病理学变化;Western Blot法检测小鼠肝脏中Nrf2、Keap1和HO-1蛋白表达.结果:最佳纯化条件:D101树脂10g,上样溶液浓度为2.0 mg/mL,上样体积为30 mL,50 mL的80％乙醇溶液洗脱,纯化后黄酮含量为70.32％±1.49％.与CON组比较,MOD组小鼠血清中AST、ALT表达显著升高(P＜0.01),说明肝损伤造模成功.与MOD组比较,给予PF组小鼠肝脏指数、AST、ALT、MDA、GSH水平和Keap 1蛋白表达显著降低25％～60％(P＜0.01 或P＜0.05),SOD、GSH-PX 水平和 Nrf2、HO-1 蛋白表达水平显著升高 15％～35％(P＜0.01 或P＜0.05).HE染色结果显示PF可有效改善APAP引起的肝损伤.结论:紫苏叶总黄酮对APAP诱导的急性肝损伤有一定的保护作用,其机制与调控氧化应激的Nrf2/HO-1信号通路相关.
Objective:To study the best purification method of Perilla flavone(PF),and to investigate its protective effect and potential mechanism on Paracetamol(APAP)-induced acute liver injury.Methods:Single factor experiments were used to determine the optimal conditions for the purification of PF by macroporous resin.BALB/c male mice were randomly divided into 6 groups,blank control group(CON),model group(MOD),diphenylene dibenzoate group(DDB),low dose group of PF(L-PF,12.5 mg/kg),middle dose group of PF(M-PF,25 mg/kg),and high dose group of PF(H-PF,50 mg/kg).DDB and PF were given by continuous intragastric administration for 15 days according to the dosage.After the last administration for 1 h,APAP was injected intraperitoneally to establish liver injury model in each group except CON group.The serum levels of AST and ALT of mice were determined,and the levels of MDA,SOD,GSH,and GSH-PX in the liver of mice were tested.HE staining of the livers was performed to observe pathological changes.The expressions of Nrf2,Keapl and HO-1 proteins in the livers were detected by Western Blot.Results:The optimal purification conditions were as follows:10 g of D101 resin,2.0 mg/mL of up-sampling solution,up-sampling volume of 30 mL,50 mL of 80％ethanol solution elution.After purification,the flavonoid content was 70.32％±1.49％.Compared with CON group,the expressions of AST and ALT in the serum were significantly higher in MOD group(P＜0.01),indicating successful modeling of liver injury.Compared with MOD group,the liver index,AST,ALT,MDA,GSH levels and Keap 1 protein expression in PF-given groups were significantly reduced by 25％～60％(P＜0.01 or P＜0.05),the concentrations of SOD,GSH-PX,and the expression levels of Nrf2 and HO-1 protein were significantly increased by 15％～35％(P＜0.01 or P＜0.05).HE staining results showed that PF could significantly improve APAP-induced liver injury.Conclusion:The PF can protect APAP-induced acute liver injury,and its mechanism is related to the Nrf2/HO-1 signaling pathway which regulates oxidative stress.
孟庆霖;褚齐;宋健;董红畅;李贺;林珈羽;赵南晰
北华大学药学院,吉林吉林 132000吉林市中心医院病理科,吉林吉林 132011
轻工业
紫苏总黄酮对乙酰氨基酚肝损伤
Perillaflavonoidsacetaminophenliver injury
《食品工业科技》 2024 (014)
344-351 / 8
吉林市科技创新发展计划项目(紫苏叶总黄酮对小鼠非酒精性肝损伤的保护作用及机制研究);北华大学自然科学青年科研创新团队(BHQNTD202202).
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