逍遥散改善卵巢切除大鼠脂代谢异常和脂肪性肝炎的作用机制  

Mechanism of Xiaoyaosan in Improving Abnormal Lipid Metabolism and Steatohepatitis of Ovariectomized Rats

作　　者：杨皓然 刘丽娜[1,2] 严晶[1] 葛飞[3] 陆玮婷[2] 史会连[2] 乔飞[2] YANG Hao-ran;LIU Li-na;YAN Jing;GE Fei;LU Wei-ting;SHI Hui-lian;QIAO Fei(The First College of Clinical Medicine,Nanjing University of Chinese Medicine,Nanjing 210046,China;Department of Hepatology,Affiliated Hospital to Nanjing University of Chinese Medicine,Nanjing 210029,China;Haian Hospital of Traditional Chinese Medicine,Haian 226600,China)

机构地区：[1]南京中医药大学第一临床医学院,南京210046 [2]南京中医药大学附属医院,南京210029 [3]海安中医院,江苏海安226600

出　　处：《中国实验方剂学杂志》2020年第3期1-7,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81603578);江苏省自然科学基金面上项目(BK20181235);江苏省中医药管理局科技项目(YB2017066);江苏高校优势学科建设工程项目。

摘　　要：目的:研究逍遥散(Xiaoyaosan,XYS)对卵巢切除(OVX)SD雌性大鼠肝脏脂代谢和脂肪性肝炎的影响及作用机制。方法:将40只雌性SD大鼠随机分为假手术组,OVX模型组,XYS低、高剂量组(3,9 g·kg^-1)。切除大鼠双侧卵巢制作去势大鼠肥胖模型,连续灌胃给药6周后,比较各组大鼠的体质量变化率、血脂及肝功能水平;苏木素-伊红(HE)染色观察肝细胞组织形态;油红染色比较肝内脂肪沉积情况;实时荧光定量聚合酶链式反应(Real-time PCR)测定肝内促炎症因子和雌激素受体β(ERβ)mRNA表达的水平。结果:与假手术组比较,OVX模型组大鼠随给药周期变化体质量变化率显著增加(2~6周,P<0.05,P<0.01);OVX模型组血清总胆固醇(TC),丙氨酸氨基转移酶(ALT),天冬氨酸氨基转移酶(AST),低密度脂蛋白(LDL)水平明显增加(P<0.05,P<0.01);肝组织学中的肝索结构紊乱,肝细胞胞浆内出现脂滴堆积;OVX模型组肝脏白细胞介素-1β(IL-1β),白细胞介素-6(IL-6)mRNA转录水平亦明显增高(P<0.05)。与OVX模型组比较,XYS低、高剂量组体质量变化率随给药周期增加均显现出不同程度的下降(3~6周);XYS可明显降低OVX模型大鼠的血清TC,ALT,AST,LDL水平(P<0.05),呈剂量依赖性;而血清甘油三酯(TG),碱性磷酸酶(AKP),高密度脂蛋白(HDL)水平各组之间无统计学意义;XYS可改善OVX模型大鼠肝细胞排列结构和脂质变性;XYS可剂量依赖地降低OVX模型大鼠肝脏IL-6,IL-1βmRNA转录水平(P<0.05,P<0.01),但肿瘤坏死因子-α(TNF-α)mRNA转录水平各组之间无显著差异;XYS低、高浓度均可提高OVX模型组肝脏ERβ的转录水平(P<0.05,P<0.01)。结论:XYS可以改善OVX模型大鼠的体质量增长率,肝脏脂质代谢异常和脂肪性肝炎,其机制可能与XYS促进肝脏ERβ表达,进而抑制肝内促炎因子表达有关。Objective:To investigate the effect of Xiaoyaosan(XYS)on hepatic lipid metabolism and steatohepatitis in ovariectomized(OVX)female SD rats and its mechanism.Method:Forty female SD rats were randomly divided into sham surgery group,OVX group,low-dose XYS group(3 g·kg^-1),and high-dose XYS group(9 g·kg^-1).Bilateral ovaries of rats were excised to replicate the obesity model of ovariectomized rat.After6 weeks of intragastric administration,the change rate of body mass in each group,the levels of blood lipids and liver function of rats were detected.Hematoxylin-eosin(HE)staining and oil red staining were used to observe the hepatocyte histomorphology and the intrahepatic fatty deposits.The expressions of hepatic proinflammatory cytokines and estrogen receptor beta(ERβ)were determined by quantitative real time polymerase chain reaction(Real-time PCR).Result:Compared with sham surgery group,the change rate of body mass of OVX group was significantly increased(2-6 weeks)with the changes in the course of drug administration and the levels of serum total cholesterol(TC),alanine aminotransferase(ALT)(P<0.05),aspartate amino transferase(AST)(P<0.01),low-density lipoprotein(LDL)(P<0.05)were markedly increased too(P<0.05,P<0.01).By histological method,in OVX group,the structure of hepatic cord became disordered,and there were new lipid droplets in hepatocyte cytoplasm,transcription levels of hepatic interleukin-1β(IL-1β)and interleukin-6(IL-6)in OVX group were significantly increased(P<0.05).Compared with OVX group,the growth rate of body weight in lowdose and high-dose XYS group showed significant decreases with the increase of the cycle of drug administration(3-6 weeks).XYS significantly reduced levels of serum TC,ALT,AST,and LDL levels of OVX rats(P<0.05)in a dose-dependent manner,while serum triglyceride(TG),alkaline phosphatase(AKP)and high-density lipoprotein(HDL)levels in the four groups showed no statistical significance,XYS can improve hepatocyte structure and steatosis of OVX rats,XYS could reduce the transcri

关 键 词：逍遥散 卵巢切除 肥胖 脂质代谢 脂肪性肝炎 雌激素受体Β 

分 类 号：R2-0[医药卫生—中医学] R22