基于Nrf2/CYP2E1通路探讨刺梨多糖对酒精性肝损伤小鼠的保护机制

Exploration of the protective mechanism of Rosa roxburghii polysaccharide against alcoholic liver injury in mice based on Nrf2/CYP2E1 pathway

中文关键词:  刺梨多糖  酒精性肝损伤  氧化应激  核因子-红细胞2相关因子2 (Nrf2)信号通路  细胞色素P450 2E1(CYP2E1)

英文关键词:Rosa roxburghii polysaccharide  alcoholic liver injury  oxidative stress  nuclear factor erythroid 2-related factor 2 signaling pathway  cytochrome P450 2E1

中文摘要:

      目的 探讨刺梨多糖(Rosa roxburghii polysaccharide, RP)对食用酒精诱导的酒精中毒小鼠肝脏的影响及保护机制。方法 采用热水浸提法制得纯度为64%的RP。将60只健康KM雄性小鼠分为空白组、模型组、阳性组、RP低、中、高剂量组, 连续给药15 d, 于末次给药4 h后, 除空白组外, 其余各组一次性灌胃16 mL/kg 50%的食用酒精建立酒精性肝损伤(alcoholic liver injury, ALI)小鼠模型; 解剖后记录脏器质量, 测定血清中谷丙转氨酶(alanine aminotransferase, ALT)、谷草转氨酶(aspartate aminotransferase, AST)、总胆固醇(total cholesterol, TC)、甘油三酯(triglyceride, TG)含量, 测定肝脏氧化应激指标含量、核因子-红细胞2相关因子2 (nuclear factor erythroid 2-related factor 2, Nrf2)信号通路相关蛋白表达量及细胞色素P450 2E1 (cytochrome P450 2E1, CYP2E1)蛋白表达量, 并进行肝脏病理和肝细胞凋亡观察。结果 与模型组相比, RP各剂量组均能降低肝脏指数、血清中ALT、AST、血脂指标TC、TG含量、肝脏丙二醛(malonaldehyde, MDA)含量, 提高谷胱甘肽(glutathione, GSH)、超氧化物歧化酶(superoxide dismutase, SOD)含量, 上调Nrf2、血红素氧合酶1 (heme oxygenase-1, HO-1)、超氧化物歧化酶1 (superoxide dismutase-1, SOD-1)蛋白表达量, 下调CYP2E1蛋白表达量, 并改善肝脏病变和肝细胞凋亡情况。结论 RP对ALI小鼠起到良好的护肝效果, 这可能与调控Nrf2信号通路起到抗氧化作用及调节脂质代谢有关。

英文摘要:

      Objective To investigate the effects of Rosa roxburghii polysaccharide (RP) on the liver of mice with alcohol-induced alcoholism and its protective mechanism. Methods RP with a purity of 64% was prepared by hot water extraction. Sixty healthy KM male mice were divided into blank group, model group, positive group, low, medium and high dose RP groups, which were given continuous administration for 15 d. After the last administration 4 h, except the blank group, the other groups were given 16 mL/kg 50% edible alcohol at one time to establish alcoholic liver injury (ALI) mouse model. After dissection, the organ mass was recorded, the content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG) in serum were determined, and the content of oxidative stress index in liver were determined. The protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and cytochrome P450 2E1 (CYP2E1) protein were observed. Liver pathology and hepatocyte apoptosis were also observed. Results Compared with model group, each dose group of RP could reduce liver index, ALT, AST, TC, TG content in serum, malondialdehyde (MDA) content in liver, and increase glutathione (GSH) and superoxide dismutase (SOD) content in liver. The expression of Nrf2, heme oxygenase 1 (HO-1) and superoxide dismutase 1 (SOD-1) protein was up-regulated, and the expression of CYP2E1 protein was down-regulated, and the liver disease and apoptosis of liver cells were improved. Conclusion RP has a good effect on liver protection in ALI mice, which may be related to the regulation of Nrf2 signaling pathway to play an antioxidant role and regulate lipid metabolism.