药学学报, 2021, 56(4): 1057-1062
引用本文:
杨婧, 范晓明, 张巧仙, 冯柯鑫, 杨榆青, 宋波, 武俊紫. 银杏内酯B调节长链脂肪酸代谢相关蛋白表达及抗氧化治疗非酒精性脂肪肝病分子机制研究[J]. 药学学报, 2021, 56(4): 1057-1062.
YANG Jing, FAN Xiao-ming, ZHANG Qiao-xian, FENG Ke-xin, YANG Yu-qing, SONG Bo, WU Jun-zi. The molecular mechanism of ginkgolide B regulating the expression of long-chain fatty acid metabolism-related proteins and antioxidant therapy for non-alcoholic fatty liver disease[J]. Acta Pharmaceutica Sinica, 2021, 56(4): 1057-1062.

银杏内酯B调节长链脂肪酸代谢相关蛋白表达及抗氧化治疗非酒精性脂肪肝病分子机制研究
杨婧1, 范晓明2, 张巧仙3, 冯柯鑫3, 杨榆青1, 宋波1*, 武俊紫1*
1. 云南中医药大学基础医学院, 云南 昆明 650404;
2. 桂林医学院, 广西系统医学重点实验室, 广西 桂林 541100;
3. 吕梁学院生命科学学院, 山西 吕梁 033000
摘要:
本文研究银杏内酯B(ginkgolide B)对非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)大鼠肝脏中长链脂肪酸代谢相关酶蛋白过氧化物酶体增殖剂激活受体α(peroxisome proliferators-activated receptors α,PPARα)、长链特异性酰基辅酶A脱氢酶(long-chain specific acyl-CoA dehydrogenase,LCAD)、肉毒碱棕榈酰转移酶-1(carnitine palmitoyl transterase-1,CPT-1)和脂酰辅酶A氧化酶1(acyl coenzyme A oxidase 1,ACOX1)表达的影响。动物福利和实验过程均遵循云南中医药大学动物伦理委员会的规定。成功建立非酒精性脂肪性肝病大鼠模型,将大鼠随机分为模型组、辛伐他汀组、银杏内酯B低、中和高剂量组,给予相应药物治疗4周。检测肝脏病理学指标并测定血液血脂、转氨酶和抗氧化指标,采用Western blot和RT-PCR法检测肝脏PPARα、LCAD、CPT-1和ACOX1蛋白及mRNA水平。结果显示:①肝脏组织病理学显示,模型组大鼠肝脏切片出现明显的结构紊乱,细胞核受到挤压,同时有明显的脂肪空泡,各治疗组相较于模型组明显好转;②与正常组相比,模型组大鼠肝功能、血脂指标明显升高,抗氧化指标则明显降低,与模型组相比,各治疗组均明显改善;③与正常组相比,模型组大鼠肝脏组织中PPARα、ACOX1、CPT-1和LCAD蛋白及mRNA表达均明显降低,相较于模型组,各治疗组均明显上调。本研究发现银杏内酯B可通过调节长链脂肪酸代谢相关蛋白PPARα、ACOX1、CPT-1和LCAD的表达,同时提高机体抗氧化能力,进而降低血脂并改善肝功能,保护肝脏。
关键词:    银杏内酯B      非酒精性脂肪肝病      脂质代谢      过氧化物酶体增殖剂激活受体α      抗氧化     
The molecular mechanism of ginkgolide B regulating the expression of long-chain fatty acid metabolism-related proteins and antioxidant therapy for non-alcoholic fatty liver disease
YANG Jing1, FAN Xiao-ming2, ZHANG Qiao-xian3, FENG Ke-xin3, YANG Yu-qing1, SONG Bo1*, WU Jun-zi1*
1. Basic Medical College, Yunnan University of Traditional Chinese Medicine, Kunming 650404, China;
2. Guangxi Key Laboratory of Systematic Medicine, Guilin Medical University, Guilin 541100, China;
3. College of Life Sciences, Lüliang University, Lüliang 033000, China
Abstract:
This study investigated the effects of ginkgolide B on the long-chain fatty acid metabolism-related enzyme protein peroxisome proliferators-activated receptors α (PPARα), long-chain specific acyl-CoA dehydrogenase (LCAD), carnitine palmitoyl transterase-1 (CPT-1), and acyl coenzyme A oxidase 1 (ACOX1) expression in the liver of rats with non-alcoholic fatty liver disease (NAFLD). All the animal welfare and experimental procedures are in accordance with the regulations of the Animal Ethics Committee of Yunnan University of Traditional Chinese Medicine. After successfully building the rat model of non-alcoholic abnormal liver disease, the rats were divided into the model group, the simvastatin group, and the low-dose, middle-dose, and high-dose groups of ginkgolide B according to random number method, and were given corresponding drug treatment 4 weeks. We detected liver pathological indicators and determined blood lipids, transaminase and anti-oxidation indexes. Western blot and RT-PCR assays were used to detect the protein and mRNA levels of PPARα, LCAD, CPT-1, and ACOX1 in livers. The results showed that:① the liver histopathology showed that the liver slices of the model group had obvious structural disorder, the nucleus was squeezed, and there were obvious fat vacuoles. The treatment groups improved significantly compared with the model group; ② compared with the normal group, the liver function and blood lipid indexes of the model group increased significantly, while the anti-oxidation indexes decreased significantly. Compared with the model group, each treatment groups were significantly improved; ③ compared with the normal group, the protein and mRNA expression levels of PPARα, ACOX1, CPT-1, and LCAD in the model group were significantly reduced, compared with the model group, those indexes in the treatment groups were significantly up-regulated. This study found that ginkgolide B could regulate the expression of long-chain fatty acid metabolism-related proteins PPARα, ACOX1, CPT-1, and LCAD, meanwhile improve the body's antioxidant capacity, thereby reduce blood lipids, further improve liver function and protect the liver.
Key words:    ginkgolide B    non-alcoholic fatty liver disease    fat metabolism    peroxisome proliferators-activated receptors α    anti-oxidation   
收稿日期: 2020-08-12
DOI: 10.16438/j.0513-4870.2020-1321
基金项目: 云南省应用基础研究计划项目(2019FF002-055).
通讯作者: 宋波,Tel:86-871-65918230,E-mail:ynkmsongbo6@126.com;武俊紫,E-mail:beached@126.com
Email: ynkmsongbo6@126.com;beached@126.com
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