| 陈皓,郭丽,于晓涛,等.灵芝提取物通过Nrf2/ARE通路对肝硬化小鼠肝功能的保护作用研究[J].浙江中医药大学学报,2024,48(1):21-29. |
| 灵芝提取物通过Nrf2/ARE通路对肝硬化小鼠肝功能的保护作用研究 |
| Protective Effect of Ganoderma Lucidum Extract on Liver Function of Cirrhotic Mice through Nrf2/ARE Pathway |
| DOI：10.16466/j.issn1005-5509.2024.01.003 |
| 中文关键词: 灵芝提取物 核因子E2相关因子2/血红素加氧酶-1信号通路 氧化应激 肝硬化 肝功能 炎症反应 肝纤维化 |
| 英文关键词: Ganoderma lucidum extract nuclear factor E2 related factor 2/heme oxygenase-1 signaling pathway oxidative stress cirrhosis liver function inflammatory reaction hepatic fibrosis |
| 基金项目:漯河市2022年度重大科技创新专项项目(2) |
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| 中文摘要: |
| [目的] 探讨灵芝提取物(ganoderma lucidum extract，GLE)对肝硬化小鼠的肝保护作用及机制。[方法] 将10只雄性C57BL/6小鼠作为对照组，剩余40只小鼠采用四氯化碳橄榄油混悬液诱导肝硬化模型，并随机分为模型组和GLE低(50 mg/kg·d)、中(100 mg/kg·d)、高(200 mg/kg·d)剂量组，对照组及模型组均灌胃等量0.9%氯化钠溶液。计算肝脏指数；以全自动生化分析仪检测小鼠血清中谷氨酸转氨酶(alanine aminotransferase，ALT)、天冬氨酸转氨酶(aspartate transaminase，AST)活性和总胆固醇(total cholesterol，TC)、总胆红素(total bilirubin，TB)和肌酐(creatinine，Cr)水平；以苏木精-伊红(hematoxylin eosin，HE)染色观察肝组织病理学变化，Masson染色观察肝组织纤维化程度；以脱氧核苷酸末端转移酶介导的dUTP缺口末端标记(terminal-deoxynucleotidyl transferase mediated dUTP nick end labeling，TUNEL)染色观察肝细胞凋亡情况；酶联免疫吸附试验(enzyme linked immunosorbent assay，ELISA)检测血清肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)、白细胞介素-1β(interleukin-1β，IL-1β)、IL-6、丙二醛(malondialdehyde，MDA)水平和超氧化物歧化酶(superoxide dismutase，SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase，GSH-Px)活性；免疫印迹法检测肝组织中总核因子E2相关因子2(nuclear factor E2 related factor 2，Nrf2)和核Nrf2、血红素加氧酶-1(heme oxygenase-1，HO-1)及醌氧化还原酶1[NAD(P)H:quinone oxidoreductase 1，NQO1]、α-平滑肌肌动蛋白(α-smooth muscle actin，α-SMA)、Ⅰ型胶原蛋白(Collagen Ⅰ)及E-钙黏蛋白(E-cadherin)的表达情况。[结果] 与对照组比较，模型组小鼠肝损伤明显，肝脏指数，血清ALT、AST活性，TC、TB及Cr水平，肝纤维化程度，肝细胞凋亡指数，血清TNF-α、IL-1β、IL-6及MDA水平，α-SMA及Collagen Ⅰ蛋白相对表达量升高(P<0.05)，血清SOD和GSH-Px活性、肝组织总Nrf2和核Nrf2、HO-1、NQO1及E-cadherin蛋白表达降低(P<0.05)。与模型组比较，GLE低、中、高剂量组小鼠肝损伤逐步减轻，肝脏指数，血清ALT、AST活性，TC、TB及Cr水平，肝纤维化程度，肝细胞凋亡指数，血清TNF-α、IL-1β、IL-6及MDA水平，α-SMA及Collagen Ⅰ蛋白表达降低(P<0.05)，血清SOD和GSH-Px活性、肝组织总Nrf2和核Nrf2、HO-1、NQO1及E-cadherin蛋白表达升高(P<0.05)。[结论] GLE可减轻肝硬化小鼠组织病理损伤，改善肝功能，这可能与激活Nrf2/ARE通路，抑制氧化应激和炎症反应，进而干预肝纤维化有关。 |
| 英文摘要: |
| [Objective] To investigate the protective effect and mechanism of Ganoderma lucidum extract(GLE) on liver cirrhosis in mice. [Methods] Ten male C57BL/6 mice were randomly selected as control group， the remaining forty mice were intraperitoneally injected with carbon tetrachloride olive oil suspension to induce liver cirrhosis model. They were randomly divided into model group and GLE low(50 mg/kg·d)， medium(100 mg/kg·d) and high(200 mg/kg·d) dose groups， while the control group and model group received 0.9% sodium chloride solution gastric irrigation， and the control group mice were given the same volume of olive oil solution twice a week. Liver index was calculated. The activities of alanine aminotransferase(ALT)， aspartate transaminase(AST) and the levels of total cholesterol(TC)， total bilirubin(TB) and creatinine(Cr) in serum of mice were detected by automatic biochemical analyzer. Hematoxylin eosin(HE) staining was used to observe the histopathological changes of liver， and Masson staining was used to observe the degree of liver fibrosis. Terminal-deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL) staining was used to observe the apoptosis of hepatocytes. The levels of tumor necrosis factor-α(TNF-α)， interleukin-1β(IL-1β)， IL-6， malondialdehyde(MDA) and activity of superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) in serum were detected by enzyme linked immunosorbent assay(ELISA). The relative expression of nuclear factor E2 related factor 2(Nrf2) and nuclear Nrf2， heme oxygenase-1(HO-1) and NAD(P)H:quinone oxidoreductase 1(NQO1)， α-smooth muscle actin(α-SMA)， Collagen Ⅰ and E-cadherin protein in liver tissue were detected by Western blot. [Results] Compared with control group， the liver had significant damage， the liver index， serum ALT， AST activities， TC， TB and Cr levels， liver fibrosis degree， hepatocyte apoptosis index， the levels of serum TNF-α， IL-1β， IL-6 and MDA， the relative expression of α-SMA and Collagen Ⅰ protein increased(P<0.05)， while the activity levels of serum SOD and GSH-Px， and the relative expression of total Nrf2 and nuclear Nrf2， HO-1， NQO1 and E-cadherin protein in liver tissue decreased in model group(P<0.05). Compared with model group， liver injury gradually reduced， the liver index， serum ALT， AST activities， TC， TB and Cr levels， liver fibrosis degree， hepatocyte apoptosis index， the levels of serum TNF-α， IL-1β， IL-6， MDA and the relative expression of α-SMA， Collagen Ⅰ protein decreased(P<0.05)， while the activity levels of serum SOD and GSH-Px， and the relative expression of Nrf2 and nuclear Nrf2， HO-1， NQO1 and E-cadherin protein in liver tissue increased in GLE low， medium and high dose groups(P<0.05). [Conclusion] GLE can alleviate the histopathological damage and improve liver function in cirrhotic mice. This may be related to the decreased level of oxidative stress and inflammatory reaction after activation of Nrf2/ARE signaling pathway， which may interfere with liver fibrosis. |
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