苦参碱对对乙酰氨基苯酚诱导的小鼠药物性肝损伤的保护作用及机制

Protective mechanism of matrine against liver injury induced by acetaminophen in mice

目的探讨苦参碱(KSJ)对对乙酰氨基苯酚(APAP)诱导的小鼠药物性肝损伤的保护作用及机制。方法雄性C57BL/6小鼠40只,随机分为空白对照组、APAP组、KSJ大剂量组[2.8 mg/(kg·d)]、KSJ中剂量组[1.4 mg/(kg·d)]和KSJ小剂量组[0.7 mg/(kg·d)],每组8只。空白对照组和APAP组小鼠尾静脉注射10%葡萄糖溶液10 ml/(kg·d);KSJ大剂量组、KSJ中剂量组和KSJ小剂量组分别注射相应浓度的KSJ葡萄糖溶液10 ml/(kg·d),连续给药7 d。末次给药后1 h,除空白对照组外其他各组小鼠腹腔注射APAP 400 mg/kg,复制急性药物性肝损伤模型,空白对照组小鼠予以等量无菌生理盐水进行一次性腹腔注射,模型复制结束后禁食不禁水24 h。24 h后,小鼠眼球采血,检测天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、超氧化物歧化酶(SOD)和丙二醛(MDA)水平;酶联免疫吸附试验(ELISA)检测IL-6、TNF-α水平;取肝脏组织行苏木精-伊红(HE)染色,观察小鼠肝脏病理学改变。结果与APAP组比较,KSJ对APAP诱导的小鼠药物性肝损伤具有一定的保护作用,包括降低血清AST和ALT水平(P<0.05),提高SOD活力,降低MDA含量(P<0.05),以及减轻肝脏病理损伤程度和肝细胞凋亡程度。同时KSJ对APAP刺激诱导产生的TNF-α和IL-6具有抑制作用(P<0.05),并且呈剂量依赖性。结论KSJ对APAP诱导的小鼠药物性肝损伤具有保护作用,其机制与降低炎症因子水平,降低氧化应激,提高抗氧化能力有关。

Objective To observe the effects of matrine(KSJ)on liver injury induced by acetaminophen(APAP)in mice.Methods Forty healthy male C57BL/6 mice were randomly divided into blank group,model group,KSJ high dose group 2.8 mg/(kg·d),KSJ medium dose group 1.4 mg/(kg·d),and KSJ low dose group 0.7 mg/(kg·d),eight in each group.Blank group and APAP group were injected with 10%glucose solution 10 ml/(kg·d)in the tail vein;KSJ high dose group 2.8 mg/(kg·d),KSJ medium dose group 1.4 mg/(kg·d),KSJ low dose group 0.7 mg/(kg·d)were injected with the corresponding concentration of matrine glucose solution 10 ml/(kg·d),continuous injection for 7 days.One hour after the last injection,acetaminophen(400 mg/kg)was injected intraperitoneally into each group except blank group to establish acute liver injury model.Equal amount of saline was injected intraperitoneally into the blank group.After the end of modeling,fasting within 24 hours but water is allowed.Serum levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),superoxide dismutase(SOD),malondialdehyde(MDA),IL-6,TNF-α,and hepatic histopathology was detected routinely after eyeball blood sampling.Results Compared with the model group,matrine has protective effects on liver injury induced by acetaminophen(APAP)in mice,including lowering serum ALT and AST levels(P<0.05),increasing SOD activity,lowering MDA content(P<0.05),and reducing the degree of liver pathological and hepatocyte apoptosis.Meanwhile,the levels of IL-6 and TNF-αwere reduced(P<0.05),and the effect was dose dependent.Conclusions Matrine can obviously decrease liver injury induced by acetaminophen(APAP)in mice,which may be related to reducing inflammatory factor levels,reducing oxidative stress,and improving antioxidant capacity.