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灯盏花素对肝纤维化大鼠的干预作用及机制
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| 篇名： | 灯盏花素对肝纤维化大鼠的干预作用及机制 |
| TITLE： | Intervention effect and mechanism of breviscapine on hepatic fibrosis in rats |
| 摘要： | 目的 基于转化生长因子β（1TGF-β1）/Smad2/胞外信号调节激酶1（ERK1）通路和Kelch样环氧氯丙烷相关蛋白1（Keap1）/核转录因子红系2相关因子2（Nrf2）/血红素加氧酶1（HO-1）通路，探讨灯盏花素对肝纤维化（HF）大鼠的干预作用及潜在机制。方法将60只大鼠随机分为正常对照组，模型组，灯盏花素低、中、高剂量组（5.4、10.8、21.6mg/kg）和秋水仙碱组（阳性对照，0.45mg/kg），每组10只，雌雄各半。除正常对照组外，其余各组大鼠均以四氯化碳诱导构建HF模型。随后，各药物组大鼠灌胃相应药液，每天1次，连续28d。观察各组大鼠的肝脏外观并计算其肝脏系数，检测其血清中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）水平和肝组织中ALT、AST、超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）水平，观察其肝组织炎症和纤维化情况，检测肝组织中TGF-β1、Smad、ERK1、Nrf2、Keap1、HO-1蛋白及mRNA的表达情况。结果与正常对照组比较，模型组大鼠肝脏可见大面积的白色结节灶、明显的炎症细胞浸润和胶原纤维沉积；其体重，肝组织中SOD、GSH-Px水平和Nrf2、HO-1蛋白及mRNA的表达水平均显著降低（P＜0.05）；肝脏系数，Masson染色阳性面积百分比，血清及肝组织中ALT、AST水平，肝组织中MDA水平和TGF-β1、Smad2、ERK1、Keap1蛋白及mRNA的表达水平显著升高（P＜0.05）。与模型组比较，各药物组大鼠肝组织病变均有所改善，上述定量指标普遍逆转（P＜0.05）。结论灯盏花素对大鼠HF有较好的干预作用，其作用可能与抑制TGF-β1/Smad2/ERK1通路来抗纤维化，调控Keap1/Nrf2/HO-1通路来抑制氧化应激有关。 |
| ABSTRACT： | OBJECTIVE To investigate the intervention effect and potential mechanism of breviscapine on hepatic fibrosis （HF） in rats based on the transforming growth factor-β（1 TGF-β1）/Smad2/extracellular signal-regulated protein kinase 1（ERK1） and Kelch-like epichlorohydrin-associated protein 1（Keap1）/nuclear factor-erythroid 2-related factor 2（Nrf2）/heme oxygenase-1（HO-1） pathways. METHODS Totally 60 rats were randomly divided into normal control group， model group， breviscapine low-dose， medium-dose and high-dose groups （5.4， 10.8， 21.6 mg/kg）， and colchicine group （positive control， 0.45 mg/kg）， with 10 rats in each group， half male and half female. Except for the normal control group， HF model of the other groups was induced by carbon tetrachloride. Subsequently， each drug group was given corresponding medicine by gavage once a day for 28 days. The liver appearance of rats in each group was observed and their liver coefficients were calculated. The levels of alanineaminotransferase （ALT） and aspartate aminotransferase （AST）in serum， those of ALT， AST， superoxide dismutase （SOD），malondialdehyde （MDA） and glutathione peroxidase （GSH- Px） in liver tissue were detected. The liver tissue inflammatory and fibrotic changes were observed. The protein and mRNA expressions of TGF-β1， Smad2， ERK1， Nrf2， Keap1 and HO-in liver tissue were detected. RESULTS Compared with the normal control group， the model group showed large areas of white nodular lesions in the liver， obvious inflammatory cell infiltration and collagen fiber deposition. The body weight， the levels of SOD and GSH-Px in liver tissue， the protein and mRNA expressions of Nrf2 and HO-1 were significantly lowered in the model group （P＜0.05）； the liver coefficient， the percentage of Masson staining positive area， ALT and AST levels of serum and liver tissue， MDA level of liver tissue， the protein and mRNA expressions of TGF-β1， Smad2， ERK1 and Keap1 were significantly increased （P＜0.05）. Compared with the model group， the liver lesions of rats in each drug group were improved， and the above quantitative indexes were generally reversed （P＜0.05）. CONCLUSIONS Breviscapine has a good intervention effect on HF rats， which may be related to inhibiting TGF-β1/Smad2/ERK1 pathway for anti-fibrosis and regulating Keap1/Nrf2/HO-1 pathway to inhibit oxidative stress. |
| 期刊： | 2024年第35卷第06期 |
| 作者： | 魏丹丹；李闪闪；张明昊；魏雨润；王红玲；柴爽爽；殷晶晶；张敏；赵菡；吴宗耀；朱奎成；王庆波 |
| AUTHORS： | WEI Dandan，LI Shanshan，ZHANG Minghao，WEI Yurun，WANG Hongling， CHAI Shuangshuang，YIN Jingjing，ZHANG Min，ZHAO Han，WU Zongyao，ZHU Kuicheng，WANG Qingbo |
| 关键字： | 灯盏花素；肝纤维化；氧化应激；转化生长因子β1/Smad2/胞外信号调节激酶 1通路；Kelch样环氧氯丙烷相关蛋白 1/核转 |
| KEYWORDS： | breviscapine； hepatic fibrosis； oxidative stress； TGF-β1/Smad2/ERK1 pathway； Keap1/Nrf2/HO-1 pathway |
| 阅读数： | 35 次 |
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