桑葚总多糖对对乙酰氨基酚诱导小鼠急性肝损伤的保护作用

Alleviation effects of total polysaccharides from fruits of Morus alba L. on acetaminophen-induced acute liver injury in mice

目的:研究桑葚总多糖(MFP)对APAP引起的HepG2肝细胞毒性的缓解效应,探讨MFP对APAP诱导小鼠急性肝损伤的保护作用及可能机制.方法:采用MTT法检测MFP对细胞活力的影响,将32只小鼠随机分为正常组、模型组、MFP低、高剂量组(50,150 mg·kg^-1),腹腔注射300 mg·kg^-1 APAP建立小鼠急性肝损伤模型,检测血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)和乳酸脱氢酶(LDH)活力,肝组织中丙二醛(MDA)、还原型谷胱甘肽(GSH)、总超氧化物歧化酶(T-SOD)和总抗氧化能力(T-AOC)水平;用ELISA测定肝组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)水平;HE染色法观察肝脏组织的病理学变化;用Western blot检测小鼠肝组织中核因子-κB(NF-κB)p65、血红素加氧酶(HO-1)和葡萄糖-6-磷酸脱氢酶(G6PD)的表达水平.结果:MFP可剂量依赖性地缓解APAP诱导的HepG2细胞死亡(P<0.01).与模型组相比,MFP能显著地降低肝损伤小鼠血清中ALT,AST,LDH水平(P<0.05或P<0.01),下调肝组织中MDA,TNF-α,IL-1β,IL-6的含量(P<0.05或P<0.01),改善APAP诱导的小鼠肝组织病变.此外,MFP还能明显上调模型小鼠肝组织中GSH,T-SOD,T-AOC水平(P<0.05或P<0.01),明显下调NF-κB p65蛋白的表达水平(P<0.05或P<0.01),上调HO-1和G6PD蛋白的表达水平(P<0.05或P<0.01).结论:MFP能保护APAP诱导的小鼠急性肝损伤,这与增强肝脏抗氧化能力,抑制肝脏炎症反应有关.

To study the alleviation effect of mulberry total polysaccharide(MFP)on HepG2 hepatocyte toxicity induced by APAP,and to explore the protective effect and possible mechanism of MFP on APAP-induced acute liver injury in mice.Methods:MTT assay was used to detect the effect of MFP on cell viability.32 mice were randomly divided into normal group,model group,MFP low and high dose group(50,150 mg·kg^-1),and mouse acute liver injury model were established by intraperitoneal injection of 300 mg·kg^-1 APAP.Serum activities of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and lactate dehydrogenase(LDH),and hepatic levels of malondialdehyde(MDA),glutathione(GSH),total superoxide dismutase(T-SOD),and total antioxidant capacity(T-AOC)were determined.Levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)in the livers were also detected.The pathological changes of liver tissue were observed by HE staining,and protein expression levels of nuclear factor-κB(NF-κB)p65,hemeoxygenase-1(HO-1)and glucose-6-phosphate dehydrogenase(G6 PD)were detected by Western blot.Results:MFP dose-dependently alleviated APAP-induced HepG2 cell death(P<0.01).Compared with the model group,MFP significantly declined levels of ALT,AST,and LDH in serum(P<0.05,P<0.01),reduced hepatic contents of MDA,TNF-α,IL-1βand IL-6(P<0.05,P<0.01),and ameliorated liver histopathological changes provoked by APAP.Moreover,MFP markedly elevated levels of GSH,T-SOD and T-AOC(P<0.05,P<0.01),decreased protein expressions of NF-κB p65(P<0.05,P<0.01),and up-regulated those of HO-1 and G6 PD(P<0.05,P<0.01).Conclusion:MFP can alleviate APAP-induced acute liver injury in mice,which is related to enhancement of the antioxidation and inflammation inhibition capacity of liver.