下瘀血汤对酒精性肝病小鼠肝脏炎症和脂肪变性的改善作用  

Effects of Xia-yu-xue decoction on improving liver inflammation and steatosis in mice with alcoholic liver disease

作　　者：马文婷 刘旭凌[1,2] 陶乐 吴柳 杨广越 张玮 沈东晓 张洁[1,2] 薛冬英[1,2] 刘成[2,3] 严萍[1,2] Ma Wenting;Liu Xuling;Tao Le;Wu Liu;Yang Guangyue;Zhang Wei;Shen Dongxiao;Zhang Jie;Xue Dongying;Liu Cheng;Yan Ping(Department of Infectious Diseases,Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China;Laboratory of Liver Disease,Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China;Central Laboratory,Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China)

机构地区：[1]上海中医药大学附属普陀医院感染科,上海200062 [2]上海中医药大学附属普陀医院肝病实验室,上海200062 [3]上海中医药大学附属普陀医院中心实验室,上海200062

出　　处：《中国肝脏病杂志（电子版）》2021年第2期40-51,共12页Chinese Journal of Liver Diseases：Electronic Version

基　　金：国家自然科学基金项目(81803232、81673788、81873136、81803898);上海市卫生健康委员会卫生行业临床研究专项(202040149);上海市普陀区卫生系统自主创新科学基金(ptkws201904);普陀医院人才类项目(培英计划2017207A)。

摘　　要：目的观察下瘀血汤对酒精性肝病(alcoholic liver disease,ALD)小鼠肝脏炎症和脂肪变性的改善作用,初步探讨其可能的作用机制。方法将48只雄性C57BL/6小鼠随机分为对照组、对照美他多辛组、对照下瘀血汤组、酒精组、酒精美他多辛组和酒精下瘀血汤组,每组各8只。对照组、对照美他多辛组和对照下瘀血汤组造模过程中全程给予液体对照饲料。酒精组、酒精美他多辛组和酒精下瘀血汤组采用4周慢性乙醇喂养加急性乙醇灌胃法造模,造模第3周第1 d起,对照下瘀血汤组和酒精下瘀血汤组小鼠以0.4678 g/kg下瘀血汤灌胃,对照美他多辛组和酒精美他多辛组小鼠以2.857 mg/kg美他多辛灌胃。其余组小鼠以等体积蒸馏水灌胃。第32 d酒精组、酒精美他多辛组和酒精下瘀血汤组小鼠以31.5%乙醇灌胃,对照组、对照美他多辛组、对照下瘀血汤组小鼠以45%糊精灌胃。9 h后处死小鼠,留取静脉血和肝脏。计算各组小鼠肝体比值,检测丙氨酸氨基转移酶(alanine aminotransferase,ALT)、血清甘油三酯(triglyceride,TG)及肝脏TG水平。采用HE染色和油红染色观察肝脏病理形态学变化。采用免疫组织化学法检测中性粒细胞标志物髓过氧化物酶(myeloperoxidase,MPO)的表达。采用实时荧光定量聚合酶链式反应(real time polymerase chain reaction,RT-PCR)检测肝组织白细胞介素-6(interleukin 6,IL-6)、白细胞介素1β(interleukin 1β,IL-1β)和单核细胞趋化蛋白1(monocyte chemotactic protein 1,MCP1)mRNA的相对表达量。采用Western blot和RT-PCR检测脂肪酸合成酶(fatty acid synthase,FAS)、肉毒碱棕榈酰基转移酶-1α(carnitine palmitoyltransferase 1α,CPT-1α)和过氧化物酶体增殖激活受体α(peroxisome proliferator-activated receptor alpha,PPARα)的表达。结果与对照组相比,酒精组小鼠肝体比值[(4.78±0.48)%vs(3.71±0.36)%]、ALT [(44.71±25.37)U/L vs(20.41±7.11)U/L]、血清TG [(4.16±1.27)mmol/L vs(1.4Objective To observe the effects of Xia-yu-xue decoction on improving liver inflammation and steatosis in mice with alcoholic liver disease(ALD)and to investigate its possible mechanism.Methods A total of 48 male C57/BL6 mice were randomly divided into blank control group,control metadoxine group,control Xia-yu-xue decoction group,alcohol group,alcohol metadoxine group and alcohol Xia-yu-xue decoction group,8 mice in each group.Mice in control group,control metadoxine group and control Xia-yu-xue decoction group were given liquid control feed throughout the process of modeling.Mice in alcohol group,alcohol metadoxine group and alcohol Xia-yu-xue decoction group were fed with ethanol liquid diet for 4 weeks and gavage with alcohol.From the 1st day of the 3rd week,mice in control Xia-yu-xue decoction group and the alcohol Xia-yu-xue decoction group were given 0.4678 g/kg of Xia-yu-xue decoction by gavage,mice in control metadoxine group and alcohol metadoxine group were given 2.857 mg/kg of metadoxine by gavage.Mice in other groups were given equal volume of distilled water by gavage.On the 32nd day,mice in alcohol group,alcohol metadoxine group and alcohol Xia-yu-xue decoction group were given 31.5%ethanol by gavage,while mice in control group,control metadoxine group and control Xia-yu-xue decoction group were given 45%dextrin.Then the mice were sacrificed 9 hours later,and venous blood and liver were collected.The ratio of liver to body weight was calculated and levels of serum alanine aminotransferase(ALT),triglyceride(TG)and liver TG contents were detected.The pathological changes of liver were observed by HE staining and oil red staining.Immunohistochemical method was used to detect the expression of myeloperoxidase(MPO),which was a marker of neutrophils in liver tissue.Real-time polymerase chain reaction(RT-PCR)was used to detect mRNA relative expression levels of interleukin 6(IL-6),interleukin 1β(IL-1β)and monocytes monocyte chemotactic protein 1(MCP1)in liver tissue.The expression of fatty acid synthase

关 键 词：下瘀血汤 酒精性肝病 炎症 脂肪变性 

分 类 号：R285.5[医药卫生—中药学]