槲皮素对黄药子致肝损伤小鼠的保护作用及其机制  

Protective effect and mechanism of quercetin on mice with liver injury induced by Dioscorea bulbifera

作　　者：王欣[1] 张雨涵 史磊磊 上官惠子 宋佳莲 安宇宇 谢允东 刘继平[1,2,3] WANG Xin;ZHANG Yuhan;SHI Leilei;SHANGGUAN Huizi;SONG Jialian;AN Yuyu;XIE Yundong;LIU Jiping(Shaanxi University of Chinese Medicine,Xianyang 712046,China;Shaanxi Key Laboratory for Safety Monitoring of Food and Drug,Xianyang 712046,China;Key Laboratory of Pharmacodynamic Mechanism and Material Basis of Chinese Medicine of Shaanxi Administration of Traditional Chinese Medicine,Xianyang 712046,China)

机构地区：[1]陕西中医药大学,陕西咸阳712046 [2]陕西省食品药品安全监测重点实验室,陕西咸阳712046 [3]陕西省中医药管理局中药药效机制与物质基础重点研究室,陕西咸阳712046

出　　处：《中草药》2024年第10期3345-3353,共9页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(82204790)。

摘　　要：目的探究槲皮素对黄药子致肝损伤的保护作用及其机制。方法将48只昆明小鼠随机分为对照组、模型组、水飞蓟宾(100 mg/kg)组和槲皮素高、中、低剂量(80、50、20 mg/kg)组。对照组ig 0.5%羧甲基纤维素钠溶液,其余各组小鼠ig相应药物及黄药子醇提物(2 g/kg),1次/d,连续30 d。实验结束后称定小鼠体质量和肝脏质量,计算肝脏指数;测定血浆中天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、超氧化物歧化酶(superoxide dismutase,SOD)活性及丙二醛(malonaldehyde,MDA)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-10(interleukin-10,IL-10)、IL-1β水平;苏木素-伊红(hematoxylin-eosin staining,HE)染色观察肝脏组织病理学变化;TUNEL染色法检测肝脏细胞凋亡情况;采用Western blotting检测肝脏核因子E2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)、磷酸化核因子-κB p65(phosphorylated nuclear factor-κB p65,p-NF-κB p65)、血红素加氧酶-1(heme oxygenase-1,HO-1)、B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)、Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)、多药耐药相关蛋白2(multidrug resistance-associated protein 2,MRP2)、尿苷二磷酸葡萄糖醛酸基转移酶1A1(uridine diphosphate-glucuronosyltransferase 1A1,Ugt1a1)、P-糖蛋白(P-glycoprotein,P-gp)表达;采用qRT-PCR检测肝脏MRP2、P-gp、Ugt1a1的mRNA表达。结果与模型组比较,槲皮素显著降低小鼠肝脏指数及肝功能(P<0.05、0.01),减轻肝脏组织病理变化,降低血浆中MDA水平(P<0.05、0.01),升高SOD活性(P<0.01),降低TNF-α、IL-1β水平(P<0.05、0.01),升高IL-10水平(P<0.01),抑制肝脏p-NF-κB p65、Bax蛋白表达(P<0.05、0.01),促进Nrf2、HO-1及药物转运体蛋白表达(P<0.05、0.01),并上调MRP2、P-gp、Ugt1a1的mRNA表达(P<0.01)。结论槲皮素对黄药子诱导的肝损伤有一定保护作用,其作用机制可能与减轻炎症、抑制细�Objective To investigate the protective effect and mechanism of quercetin against Dioscorea bulbifera(DB)-induced liver injury.Methods A total of 48 KM mice were randomly divided into control group,model group,silybin(100 mg/kg)group,and quercetin high-,medium-,low-dose(80,50,20 mg/kg)groups.Mice in control group was ig 0.5%CMC-Na solution.The remaining groups were administered with drug and ethanol extract(2 g/kg)of DB,once a day for 30 d.After the experiment,the body weight and liver weight were measured and liver index was calculated;Activities of aspartate aminotransferase(AST),alanine aminotransferase(ALT),superoxide dismutase(SOD),and levels of malonaldehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),IL-1βin plasma were detected;Pathological changes in liver were observed by hematoxylin-eosin staining(HE);Apoptosis of liver cells was detected using TUNEL staining;Western blotting was used to determine protein expressions of nuclear factor erythroid 2-related factor 2(Nrf2),phosphorylated nuclear factor-κB p65(p-NF-κB p65),heme oxygenase-1(HO-1),B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),multidrug resistance-associated protein 2(MRP2),uridine diphosphate-glucuronosyltransferase1A1(Ugt1a1)and P-glycoprotein(P-gp)in liver;qRT-PCR was used to detect mRNA expressions of MRP2,P-gp and Ugt1a1 in liver.Results Compared with model group,quercetin significantly reduced liver index and liver function(P<0.05,0.01),reduced pathological change in liver tissue,reduced MDA level in plasma(P<0.05,0.01),increased SOD activity(P<0.01),reduced levels of TNF-α,IL-1β(P<0.05,0.01),increased IL-10 level(P<0.01),inhibited p-NF-κB p65 and Bax protein expressions in liver(P<0.05,0.01),promoted Nrf2,HO-1 and drug transporter protein expressions(P<0.05,0.01),and up-regulated the mRNA expressions of MRP2,P-gp and Ugt1a1(P<0.01).Conclusion Quercetin has a certain protective effect on DB-induced liver injury,and its mechanism may be related to reducing inflammation,inhibiting cell apoptosis,regulating

关 键 词：槲皮素 黄药子 肝损伤 炎症 凋亡 核因子E2相关因子2 药物转运体 

分 类 号：R285.5[医药卫生—中药学]