香叶木素对非酒精性脂肪肝病幼鼠的保护作用

doi:10.13418/j.issn.1001-165x.2018.05.008

中国临床解剖学杂志 ›› 2018, Vol. 36 ›› Issue (5): 520-526.doi: 10.13418/j.issn.1001-165x.2018.05.008

香叶木素对非酒精性脂肪肝病幼鼠的保护作用

郑方芳¹，　郭新铭²，　钟北龙³，　蒋小云⁴

1.中山大学附属第五医院儿科， 2.药学部, 3.胸心外科，广东珠海 519000; 4.中山大学附属第一医院儿科，广州 510080

收稿日期:2018-05-28 出版日期:2018-09-25 发布日期:2018-10-26
通讯作者: 蒋小云，教授，主任医师，博士生导师，E-mail:?xyjiang-3208@163.com
作者简介:郑方芳（1979-），主治医师，研究方向：小儿肾脏病学，Tel：13926927870，E-mail：lmr18571531199 @sina.com
基金资助:
广东省科技计划项目（2014A020212140）；广州市科技计划项目（201607010284）；珠海市科技计划项目（20161027E030070）

The protective effect of diosmetin on non-alcoholic fatty liver disease of young rats

ZHENG Fang-fang¹, GUO Xin-ming², ZHONG Bei-long³, JIANG Xiao-yun⁴

1.Department of Pediatrics; 2. Department of faculty of pharmaceutical Sciences; 3. Department of Thoracic Surgery, the Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, Guangdong Province , China; 4. Department of Pediatrics, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China

Received:2018-05-28 Online:2018-09-25 Published:2018-10-26

摘要/Abstract

摘要：

目的　探索香叶木素对高脂饮食诱导的非酒精性脂肪肝病幼鼠的影响。方法　高脂饮食诱导非酒精性脂肪肝病大鼠模型。酶联免疫吸附实验（enzyme-linked immunosorbent assay, ELISA）检测血脂及炎症因子水平。苏木素伊红（hematoxylin- eosin, HE）染色和脱氧核糖核苷酸末端转移酶介导的缺口末端标记（terminal deoxynucleotidyl transferase- mediated dUTP nick labeling, TUNEL）染色分析肝脏组织病变及细胞凋亡。蛋白印记检测p-AMPKα1，AMPKα1，CPT-1， PPAR-α，SREBP-1c，FAS，p-P38，P38，p-AKT，AKT，p-AKT，AKT表达。结果　与对照组相比，高脂饮食组大鼠TC, TG, LDL-c水平升高，HDL-c水平下降（P<0.01）。与高脂饮食组相比，香叶木素（10, 20, 50 mg/kg）组大鼠TC, TG, LDL-c水平降低，HDL-c水平上升（P<0.01）。香叶木素可缓解高脂饮食诱导的肝脏组织病变。高脂饮食组大鼠肝脏组织细胞凋亡高于对照组（P<0.01）。香叶木素（10, 20, 50 mg/kg）组大鼠肝脏组织细胞凋亡低于高脂饮食组（P<0.01）。高脂饮食组大鼠p-AMPKα1，CPT-1 和PPAR-α 表达低于对照组（P< 0.01）。与高脂饮食组相比，香叶木素（20, 50 mg/kg）组大鼠p-AMPKα1，CPT-1 和PPAR-α 表达升高（P< 0.01）。高脂饮食组大鼠SREBP-1c 和FAS表达高于对照组（P<0.01）。与高脂饮食组相比，香叶木素（10, 20, 50 mg/kg）组大鼠SREBP-1c 和FAS表达下降（P<0.01）。而且，高脂饮食组大鼠IL-6, IL-1β和TNF-α水平高于对照组（P<0.01）。与高脂饮食组相比，香叶木素（20, 50 mg/kg）组大鼠IL-6, IL-1β和TNF-α水平下降（P<0.01）。另外，香叶木素可逆转compound C对AMPK通路的抑制作用。结论　香叶木素激活AMPK通路减轻高脂饮食诱导的非酒精性脂肪肝病幼鼠脂质代谢异常，肝脏组织病变，细胞凋亡及炎症反应。

关键词: 香叶木素, 　非酒精性脂肪肝病, 　脂代谢, 　肝损伤, 　AMPK通路, 　炎症

Abstract:

Objective　To explore the effect of diosmetin on non-alcoholic fatty liver disease of young rats induced by high-fat diet.　Methods　The rats models of non-alcoholic fatty liver disease were induced by high-fat diet. The levels of serum lipid and inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The pathological changes and apoptosis of liver tissues were observed by hematoxylin- eosin (HE) staining and terminal deoxynucleotidyl transferase- mediated dUTP nick labeling (TUNEL). The levels of p-AMPKα1, AMPKα1, CPT-1, PPAR-α, SREBP-1c, FAS, p-P38, P38, p-AKT, AKT, p-AKT, AKT were tested by western blot.　Results　Compared with control group, the levels of TC, TG, LDL-c in high fat diet group were increased with declined levels of HDL-c (P<0.01). Compared with high fat diet group, the levels of TC, TG, LDL-c in diosmetin (10, 20, 50 mg/kg) groups were reduced with enhanced levels of HDL-c (P<0.01). The high fat diet-induced pathological changes of liver tissues were reliefed by diosmetin. The apoptosis of liver tissues in high fat diet group was higher than that of control group (P<0.01). The apoptosis of liver tissues in diosmetin (10, 20, 50 mg/kg) groups was lower than that of high fat diet group (P<0.01). The levels of p-AMPKα1, CPT-1 and PPAR-α in high fat diet group were lower than that of control group (P<0.01). Compared with high fat diet group, the levels of p-AMPKα1, CPT-1 and PPAR-α in diosmetin (20, 50 mg/kg) groups were elevated (P<0.01). The levels of SREBP-1c and FAS in high fat diet group were higher than that of control group (P<0.01). Compared with high fat diet group, the levels of SREBP-1c and FAS in diosmetin (10, 20, 50 mg/kg) groups were decreased (P<0.01). Moreover, the levels of IL-6, IL-1β and TNF-α in high fat diet group were higher than that of control group (P<0.01). Compared with high fat diet group, the levels of IL-6, IL-1β and TNF-α in diosmetin (20, 50 mg/kg) groups were reduced (P<0.01). In addition, the inhibitory effect of compound C on AMPK pathway was reversed by diosmetin. Conclusion Diosmetin alleviates the abnormal lipid metabolism, pathological changes of liver tissues, apoptosis and inflammatory response in high-fat diet-induced non-alcoholic fatty liver disease rats by activating AMPK pathway.

Key words: Diosmetin;　Non-alcoholic fatty liver disease; , Lipid metabolism; , Liver injury; , AMPK pathway; , Inflammation

郑方芳，郭新铭，钟北龙，蒋小云. 香叶木素对非酒精性脂肪肝病幼鼠的保护作用[J]. 中国临床解剖学杂志, 2018, 36(5): 520-526.

ZHENG Fang-fang, GUO Xin-ming, ZHONG Bei-long, JIANG Xiao-yun. The protective effect of diosmetin on non-alcoholic fatty liver disease of young rats[J]. Chinese Journal Of Clinical Anatomy, 2018, 36(5): 520-526.

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香叶木素对非酒精性脂肪肝病幼鼠的保护作用

The protective effect of diosmetin on non-alcoholic fatty liver disease of young rats

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