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、抑制细胞凋亡、调控Nrf2及药物转运体的表达相关。

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-1β in 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 the expression of Nrf2 and drug transporters.

R285.5

国家自然科学基金资助项目（82204790）