矮地茶黄酮对大鼠肝纤维化保护作用及机制研究  

Protective effect and mechanism of flavonoids of Ardisa japonica on liver fibrosis in rats

作　　者：曹庆生[1] 李志超 韩立旺 CAO Qing-sheng;LI Zhi-chao;HAN Li-wang(Department of Pathology,Yutian Hospital of Tangshan City in Hebei Province,Yutian064100,China;Department of Pain,Yutian Traditional Chinese Medicine Hospital of Tangshan City in Hebei Province,Yutian064100,China)

机构地区：[1]河北省唐山市玉田县医院病理科,河北玉田064100 [2]河北省唐山市玉田县中医医院疼痛科,河北玉田064100

出　　处：《中国当代医药》2020年第13期4-8,F0003,共6页China Modern Medicine

基　　金：河北省“三三三人才工程”培养经费资助项目(A201901133)。

摘　　要：目的研究矮地茶黄酮对肝纤维化的保护作用及相关机制。方法随机将60只大鼠分为正常组、模型组、矮地茶黄酮高剂量组(600 mg/kg)、矮地茶黄酮中剂量组(400 mg/kg)和矮地茶黄酮低剂量组(200 mg/kg),每组各12只。采用腹腔注射0.5%二甲基亚硝胺的方法制备肝纤维化模型,同时,各用药组灌服矮地茶黄酮,每天1次,共8周。观察大鼠的一般形态,检测大鼠血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、超氧化物歧化酶(SOD)、丙二醛(MDA)、透明质酸(HA)、层粘连蛋白(LN)水平,苏木素-伊红(HE)染色观察大鼠的肝脏变化,免疫组化方法检测各组大鼠调控转化生长因子-β1(TGF-β1)、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-1(MMP-1)及基质金属蛋白酶抑制剂-1(TIMP-1)表达情况。结果矮地茶黄酮高、中剂量组大鼠的血清ALT、AST、MDA、HA、LN水平低于模型组,SOD水平高于模型组,肝脏炎症程度和纤维化程度均好于模型组,TGF-β1、TNF-α、TIMP-1表达阳性率低于模型组,MMP-1表达阳性率高于模型组,差异均有统计学意义(P<0.05);矮地茶黄酮低剂量组大鼠的血清ALT、AST、MDA、LN水平低于模型组,差异有统计学意义(P<0.05),SOD、HA水平与模型组比较,差异无统计学意义(P>0.05),炎症程度及纤维化程度与模型组比较,差异无统计学意义(P>0.05),TGF-β1、TNF-α、MMP-1及TIMP-1的表达阳性率与模型组比较,差异无统计学意义(P>0.05)。结论矮地茶黄酮对肝纤维化具有保护作用,并与剂量有关;其作用机制可能与保护肝细胞、降低炎症程度、防止氧化应激的发生,抑制肝星状细胞的活化、减少细胞外基质形成有关。Objective To study the protective effect and mechanism of flavonoids of Ardisa japonica(FAJ)on liver fibrosis.Methods Sixty rats were randomly divided into a normal control group,a model group,a high-dose of FAJ group(600 mg/kg),a medium-dose of FAJ group(400 mg/kg),and a low-dose of FAJ group(200 mg/kg),with 12 rats in each group.Hepatic fibrosis model was prepared by intraperitoneal injection of 0.5%dimethylnitrosamine.At the same time,each group with intervention was administered with FAJ once a day for 8 weeks.The general morphology of rats was observed.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),superoxide dismutase(SOD),malondialdehyde(MDA),hyaluronic acid(HA),and laminin(LN)were tested.The changes of liver in rats were observed via hematoxylin-eosin(HE)staining,and the expression of transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),matrix metalloproteinase-1(MMP-1),tissue inhibitor of matrix metalloproteinase-1(TIMP-1)was detected using immunohistochemical methods.Results The levels of ALT,AST,MDA,HA,and LN in the serum of rats in the high and medium-dose of FAJ groups were lower than those in the model group,and the SOD levels were higher than those in the model group,the degree of inflammation and fibrosis of liver was better compared with that in the model group,the positive rates of expression of TGF-β1,TNF-α,TIMP-1 were lower than those of the model group,and the positive rates of expression of MMP-1 were higher than those of the model group,the differences were statistically significant(P<0.05).The serum levels of ALT,AST,MDA,and LN in rats in the low-dose of FAJ group were lower than those in the model group,and the differences were statistically significant(P<0.05).There were no significant differences in the levels of SOD or HA when compared with the model group(P>0.05).There were no significant differences in the degree of inflammation and fibrosis compared with the model group(P>0.05).There were no significant differences in the posi

关 键 词：矮地茶黄酮 肝纤维化 二甲基亚硝胺 免疫组化 

分 类 号：R285.5[医药卫生—中药学]