[关键词]
[摘要]
目的 探讨红花提取物(Carthamus tinctorius L. extract,CTLE)对乙醇诱导的酒精性肝病小鼠氧化应激和炎 症水平的影响及其作用机制。方法 SPF 级 C57BL/6 雄性小鼠随机分为 4 组:对照组、模型组、红花提取物低剂 量组(50 mg·kg-1 )、红花提取物高剂量组(100 mg·kg-1 )。对照组给予 Lieber-Decarli 液体饲料,其他组给予 LieberDecarli 酒精饲料构建小鼠慢性酒精性肝损伤模型。收集小鼠血清和肝组织,检测小鼠血清生化指标。通过 HE 和 油红 O 染色观察小鼠肝组织病理变化。qRT-PCR 和 Western Blot 法检测 Keap1/Nrf2 和 STAT3/NF-κB 通路相关因 子的 mRNA 和蛋白表达水平。结果 与模型组比较,给药组丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、低密 度脂蛋白胆固醇(LDL-C)、丙二醛(MDA)的水平明显降低(P<0.05,P<0.01),而高密度脂蛋白胆固醇(HDL-C)、 超氧化物歧化酶(SOD)和谷胱甘肽(GSH)的水平明显升高(P<0.05,P<0.01),表明红花提取物对小鼠酒精性肝 损伤具有一定的保护和抗氧化作用; HE 染色和油红 O 染色观察到小鼠肝脏病变和脂质沉积有所改善。并且通 过激活 Keap1/Nrf2 通路相关抗氧化因子的 mRNA 和蛋白表达水平,抑制 STAT3/NF-κB 通路及相关炎症因子的 mRNA 和蛋白表达水平(P<0.05,P<0.01),从而增强机体的抗氧化和抗炎作用。结论 红花提取物可以通过调节 Keap1/ Nrf2 和 STAT3/NF-κB 信号通路发挥抗氧化应激和抗炎作用,减轻小鼠的酒精性肝损伤,为治疗酒精性肝病和后 续分子机制研究提供新的思路。
[Key word]
[Abstract]
Objective To investigate the effects of Carthamus tinctorius L. extract (CTLE) on the levels of oxidative stress and inflammation in mice with ethanol-induced alcoholic liver disease and its mechanism of action. Methods SPF-grade C57BL/6 male mice were randomly divided into four groups:control group,model group,low-CTLE group (50 mg·kg-1 ),and high-CTLE group (100 mg·kg-1 ). The control group was given Lieber-Decarli liquid diet, and the other groups were given Lieber-Decarli alcohol diet to construct a chronic alcoholic liver injury model in mice. Serum and liver tissues of mice were collected and serum biochemical indexes of mice were detected. HE and oil red O staining were applied to observe pathological changes in mouse liver tissues. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression levels of Keap1/Nrf2 and STAT3/NF- κB pathway-related factors. Results Compared with the model group,the ALT,AST,LDL-C,and MDA levels were significantly reduced (P<0.05,P<0.01),while the levels of HDL-C,SOD,and GSH were increased dramatically in the administered group (P<0.05, P<0.01), which indicated that CTLE has specific protective and antioxidant effects on alcoholic liver injury in mice. HE staining and oil red O staining showed that the hepatic lesions and lipid deposition of mice were ameliorated. It enhances the antioxidant and anti-inflammatory effects of the body by activating the mRNA and protein expression levels of antioxidant factors related to the Keap1/ Nrf2 pathway and inhibiting the mRNA and protein expression levels of inflammatory factors related to STAT3/ NF- κB pathway (P<0.05,P<0.01). Conclusion It was shown that CTLE could exert anti-oxidative stress and anti-inflammatory effects through regulating Keap1/Nrf2 and STAT3/NF-κB signaling pathways to attenuate alcoholic liver injury in mice. This study may provide a new idea for the treatment of alcoholic liver disease and the subsequent study of molecular mechanisms.
[中图分类号]
R285.5
[基金项目]
国家自然科学地区基金(82160121)