小白薇不同萃取物对非酒精性脂肪性肝炎的改善作用及机制
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篇名: 小白薇不同萃取物对非酒精性脂肪性肝炎的改善作用及机制
TITLE: Improvement effect and mechanism of different extracts from Tylophora yunnanensis on non-alcoholic steato-hepatitis
摘要: 目的 探讨小白薇不同萃取物对非酒精性脂肪性肝炎(NASH)的改善作用和作用机制。方法用游离脂肪酸诱导人正常肝细胞LO2脂肪变性,实验分为正常组、模型组、水飞蓟宾组(100μmol/mL)、小白薇乙醇萃取物(TYS)组(50μg/mL)、小白薇乙酸乙酯萃取物(TYSA)组(50μg/mL)、小白薇正丁醇萃取物(TYSB)组(50μg/mL),药物干预24h后观察各组LO2细胞内的脂滴沉积情况,检测细胞内总胆固醇(TC)、三酰甘油(TG)、丙二醛(MDA)、谷胱甘肽(GSH)含量和天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、超氧化物歧化酶(SOD)活性以及Kelch样环氧氯丙烷相关蛋白1(Keap1)、核因子E2相关因子2(Nrf2)、血红素氧合酶1(HO-1)mRNA表达水平。用高脂饮食诱导建立NASH大鼠模型,实验分为正常组、模型组、水飞蓟宾组(12.6mg/kg)、TYS组(80mg/kg)、TYSA组(80mg/kg)、TYSB组(80mg/kg),每组6只。药物干预6周后计算各组大鼠的肝脏指数,观察肝脏病理形态变化,检测血清中TC、TG、HDL-C、LDL-C含量和AST、ALT活性以及肝组织中MDA、GSH含量和SOD活性。结果与模型组比较,TYS、TYSA、TYSB可降低LO2细胞脂肪变性后的脂滴沉积和细胞内TC、TG、MDA含量以及AST、ALT活性,升高SOD活性、GSH含量和Keap1、Nrf2、HO-1mRNA表达水平,部分差异有统计学意义(P<0.05);还可显著改善NASH模型大鼠的肝损伤,降低其肝脏指数和TC、TG、LDL-C、MDA含量以及AST、ALT活性,升高HDL-C(TYS、TYSB除外)、GSH含量和SOD活性,以TYSA效果最明显(P<0.05)。结论TYS、TYSA、TYSB对NASH具有一定的改善作用,其中TYSA效果最明显;其作用机制可能与上调Keap1/Nrf2/HO-1信号通路,抑制氧化应激有关。
ABSTRACT: OBJECTIVE To investigate the improvement effect and mechanism of different extracts from Tylophora yunnanensis on non-alcoholic steatohepatitis (NASH). METHODS Normal human liver LO2 cells were induced to steatosis by free fatty acid, then were divided into normal group, model group, silybin group (100 μmol/mL), T. yunnanensis ethanol extracts (TYS) group (50 μg/mL), T. yunnanensis ethyl acetate extracts (TYSA) group (50 μg/mL), and T. yunnanensis n-butanol extracts (TYSB) group (50 μg/mL). After 24 hours of drug intervention, the deposition of lipid droplets was observed in LO2 cells in each group. The contents of total cholesterol (TC), triacylglycerol (TG), malondialdehyde (MDA) and glutathione (GSH), the activities of aspartate transaminase (AST), alanine transaminase (ALT) and superoxide dismutase (SOD), the mRNA expressions of Kelch-like ECH-associated protein 1( Keap1), nuclear factor E2-related factor 2( Nrf2) and heme oxygenase 1( HO- 1) were detected. NASH rat model was induced by a high-fat diet, and then divided into normal group, model group, silybin group (12.6 mg/kg), TYS group (80 mg/kg), TYSA group (80 mg/kg) and TYSB group (80 mg/kg), with six rats in each group. The liver indexes of rats in each group were calculated after 6 weeks of drug intervention. The liver histopathological changes were observed, and the contents of TC, TG, HDL-C and LDL-C, AST and ALT activities in serum, the contents of MDA and GSH, SOD activities in liver tissue were detected. RESULTS Compared with model group, TYS, TYSA and TYSB could reduce lipid droplet deposition, intracellular TC, TG and MDA contents, AST and ALT activities, and increase SOD activity, GSH content, and Keap1, Nrf2, HO-1 mRNA expression levels in LO2 cells after steatosis to varying degrees, with some differences being statistically significant (P<0.05). They also significantly improved liver injury in NASH model rats, reduced their liver indexes, TC, TG, LDL-C and MDA contents, AST and ALT 1-042) activities, and increased HDL-C (except for TYS and TYSB), GSH contents and SOD activity, with TYSA having the most significant effect (P<0.05). CONCLUSIONS TYS, TYSA and TYSB have a certain improvement effect on NASH, among which TYSA has the most obvious effect. Its mechanism of action may be related to upregulating the Keap1/Nrf2/HO-1 signaling pathway and inhibiting oxidative stress
期刊: 2023年第34卷第10期
作者: 乔雪;李欣坪;薛咏梅;方琼莲;王蒙蒙;林玉萍
AUTHORS: QIAO Xue,LI Xinping,XUE Yongmei,FANG Qionglian,WANG Mengmeng,LIN Yuping
关键字: 小白薇;非酒精性脂肪性肝炎;游离脂肪酸;正常肝细胞LO2;肝功能;抗氧化活性;大鼠
KEYWORDS: Tylophora yunnanensis; non-alcoholic steatohepatitis; free fatty acids; normal liver cells LO2; liver function;
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