胡黄连苷Ⅱ对CCl_(4)致大鼠急性肝损伤的保肝利胆作用研究  

Study on hepatoprotective and choleretic effects of picrosideⅡon CCl_(4)-induced acute liver injury in rats

作　　者：谭琴[1] 李鹏[1] 丁选胜[2] TAN Qin;LI Peng;DING Xuansheng(Yangtze River Pharmaceutical Co.,Ltd.,Taizhou 225321,China;China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]扬子江药业集团有限公司,江苏泰州225321 [2]中国药科大学,江苏南京211198

出　　处：《药物评价研究》2022年第7期1343-1349,共7页Drug Evaluation Research

摘　　要：目的研究胡黄连苷Ⅱ对四氯化碳(CCl_(4))诱导的大鼠急性肝损伤的保肝和利胆作用。方法保肝作用和利胆作用研究各选取60只健康SD大鼠,均随机分为6组:对照组、模型组、溶剂对照组和胡黄连苷Ⅱ低、中、高剂量(2.5、5.0、10.0 mg·kg^(−1))组,除对照组外,其余5组大鼠分别1次性ip给予CCl_(4)油溶液(50%橄榄油、2 mL·kg^(−1))制备急性肝损伤模型。保肝作用研究:在造模后3、24和48 h ig给药1次,对照组和模型组ig给予等体积生理盐水,溶剂对照组ig给予等体积溶剂,试剂盒法检测血清中丙氨酸氨基转移酶(ALT)、天氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、总胆红素(TBIL)、总胆汁酸(TBA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)及白细胞介素-6(IL-6)水平和肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽S转移酶(GST)、谷胱甘肽(GSH)及谷胱甘肽过氧化物酶(GSH-Px)水平;HE染色观察肝组织病理改变。利胆作用研究:大鼠造模12 h之后进行胆管插管,并通过十二指肠给药,给药前及给药后30、60、90及120 min分别记录胆汁流量。结果与模型组比较,胡黄连苷Ⅱ能显著降低血清中肝功能生化指标ALT、AST、ALP、TBA和TBIL水平(P<0.01);显著降低大鼠肝脏MDA水平,并显著增加肝脏SOD、CAT、GSH、GST及GSH-Px水平(P<0.01);显著降低血清TNF-α、IL-6及IL-8水平(P<0.01),且呈剂量相关性。胡黄连苷Ⅱ各剂量均可不同程度减轻模型大鼠肝脏病变范围与程度。与模型组比较,各给药后时间点胡黄连苷Ⅱ均可显著增加胆汁流量(P<0.01),且呈剂量相关性。结论胡黄连苷Ⅱ能显著缓解CCl_(4)诱导的大鼠急性肝损伤并增加胆汁流量。Objective To study the hepatoprotective and choleretic effects of picroside Ⅱ on carbon tetrachloride(CCl_(4))-induced acute liver injury in rats.Methods Sixty healthy SD rats were selected respectively for liver protection and cholagogic effects,and were randomly divided into six groups respectively:control group,model group,solvent control group and picroside Ⅱ low-dose,medium-dose and high-dose(2.5,5.0,10.0 mg·kg^(−1))groups.Except for the control group,rats were given CCl_(4)oil solution(50%olive oil,2 mL·kg^(−1))by ip once to prepare acute liver injury model.Study on liver protection:The drug was administered once at 3,24 and 48 h after modeling,control group and model group were ig given equal volume of normal saline,and solvent control group was ig given equal volume of solvent.The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),total bilirubin(TBIL),total bile acid(TBA),tumor necrosis factor-α(TNF-α),interleukin-8(IL-8)and interleukin-6(IL-6)in serum and malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT),glutathione S transferase(GST),glutathione(GSH)and glutathione peroxidase(GSH-Px)in liver tissues were detected by kit method.HE staining was used to observe the pathological changes of liver tissue.Cholagogic effect study:Bile duct intubation was performed 12 h after rat modeling,and bile flow was recorded before and 30,60,90 and 120 min after administration.Results Compared with model group,picrosideⅡcould significantly reduce the levels of ALT,AST,ALP,TBA and TBIL in serum(P<0.01),increased the levels of SOD,CAT,GSH,GST and GSH-Px in liver significantly(P<0.01),significantly decreased serum TNF-α,IL-6 and IL-8 levels(P<0.01),in a dose-dependent manner.The range and degree of liver lesions in model rats could be alleviated by different doses of picrosideⅡ.Compared with model group,picrosideⅡsignificantly increased bile flow at time points after administration(P<0.01),in a dose-dependent manner.Conclusion Picroside Ⅱ could a

关 键 词：胡黄连苷Ⅱ 急性肝损伤 肝脏保护 利胆 氧化应激 炎症 

分 类 号：R285.5[医药卫生—中药学]