首页|基于Nrf2-Keap1通路探讨小槐花不同提取物对CCl4所致肝损伤的保护机制

基于Nrf2-Keap1通路探讨小槐花不同提取物对CCl4所致肝损伤的保护机制

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目的 探讨小槐花不同提取物对CCl4所致肝损伤的保护机制.方法 采用0.5％CCl4花生油溶液构建小鼠肝损伤模型.苏木精-伊红(hematoxylin-eosin staining,HE)染色观察肝脏病变;试剂盒检测丙氨酸转氨酶(alanine amin-otransferase,ALT)、天冬氨酸转氨酶(aspartate aminotransferase,AST)、丙二醛(malondialdehyde,MDA)、还原型谷胱甘肽(glutathione,GSH)、超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、活性氧(reactive oxygen species,ROS)水平;Western blot检测肝脏组织中核因子促红细胞生成素2相关因子2(nuclear factor erythropoietin-2-related factor 2,Nrf2)、Kelch 样环氧氯丙烷相关蛋白 1(Kelch like epichlorohydrin related protein-1,Keap1)、血红素加氧酶 1(heme oxyge-nase 1,HO-1)蛋白的相对表达量.结果 与模型组相比,小槐花水提物与醇提物中、高剂量组能显著降低肝重指数以及血清中ALT、AST水平(P＜0.05,P＜0.01).小槐花水提物与醇提物中、高剂量组小鼠肝组织匀浆MDA、TNF-α、IL-6、ROS含量显著降低(P＜0.05,P＜0.01),SOD、CAT酶活性显著升高(P＜0.05,P＜0.01),GSH含量显著升高(P＜0.05,P＜0.01).其中小槐花水提物作用效果优于醇提物.小槐花水提物高剂量组显著上调Nrf2、HO-1,下调Keap1蛋白的表达(P＜0.05).结论 小槐花不同提取物对CCl4肝损伤小鼠具有保护作用,水提物保肝效果优于醇提物,作用机制与激活Nrf2-Keap1通路,减轻氧化应激反应有关.
Exploring Protective Mechanism of Different Extracts of Xiaohuaihua[Desmodium caudatum(Thunb.)DC.]Against Liver Injury Induced by CCl4 Based on Nrf2-Keap1 Pathway
Objective To explore the protective mechanism of different extracts of Xiaohuaihua[Desmodium caudatum(Thunb.)DC.]on CCl4 induced liver injury.Methods 0.5％CCl4 peanut oil solution was used to establish a mouse liver inju-ry model.HE staining was used to observe liver lesions.The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD),catalase(CAT),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and reactive oxygen species(ROS)were detected by the kits.The protein levels of nuclear factor erythropoietin-2-related factor 2(Nrf2),Kelch like epichlorohydrin related protein-1(Keap1)and heme oxygenase 1(HO-1)were analyzed by Western blot.Results Compared with the model group,medium and high dose groups of water extract and alcohol extract of Xiaohuaihua[Desmodium caudatum(Thunb.)DC.]significantly decreased liver weight index and serum levels of ALT and AST(P＜0.05,P＜0.01).The contents of MDA,TNF-α,IL-6 and ROS in liver homogenate of mice in medium and high dose groups of water extract and alcohol extract of Xiaohuaihua[Desmodium caudatum(Thunb.)DC.]were significantly decreased(P＜0.05,P＜0.01),the activities of SOD and CAT were significantly increased(P＜0.05,P＜0.01)and GSH content was significantly increased(P＜0.05,P＜0.01).The effect of water extract of Xiaohuaihua[Desmodium cau-datum(Thunb.)DC.]was better than that of alcohol extract.The high dose group of water extract of Xiaohuaihua[Desmodium caudatum(Thunb.)DC.]significantly improved the protein levels of Nrf2 and HO-1 and reduced Keap1 protein expression(P＜0.05).Conclusion Different extracts of Xiaohuaihua[Desmodium caudatum(Thunb.)DC.]showed protective effects on mice with liver injury induced by CCl4 and the liver protection effect of water extract was better than that of alcohol extract.The mechanism of action was related to activating Nrf2-Keap1 pathway and alleviating oxidative stress reaction.

extracts of Xiaohuaihua[Desmodium caudatum(Thunb.)DC.]liver injuryNrf2-Keap1 pathwayoxidative stress

钟华帅、曾勇珠、陆建媚、苏晓丹、吴伟森、覃裕翠、陆国寿、叶勇

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广西医科大学药学院,广西南宁 530021

广西壮族自治区中医药研究院,广西南宁 530022

广西生物活性分子研究与评价重点实验室,广西南宁 530000

小槐花提取物 肝损伤 Nrf2-Keap1通路 氧化应激

国家自然科学基金项目国家自然科学基金项目广西自然科学基金项目广西自然科学基金项目广西自然科学基金项目广西高校中青年教师科研基础能力提升基金项目广西高校中青年教师科研基础能力提升基金项目

81960756813606892022GXNSFDA0350632018GXNSFAA0500782015GXNSFAA1391732019KY01482019KY0315

2024

10.13193/j.issn.1673-7717.2024.04.025

中华中医药学刊
中华中医药学会 ,辽宁中医药大学

中华中医药学刊

CSTPCD北大核心
影响因子：1.007
ISSN：1673-7717
年,卷(期)：2024.42(4)
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