护肝布祖热颗粒通过抑制凋亡减轻小鼠免疫性肝损伤  

Hugan Buzure Granule Reduces Immune Liver Injury in Mice by Inhibiting Apoptosis

作　　者：王梦恒 但汉雄[1] 罗来春[1] 刘焱文[1] 尹海龙 尹强 尤朋涛[1] Wang Mengheng;Dan Hanxiong;Luo Laichun;Liu Yanwen;Yin Hailong;Yin Qiang;You Pengtao(Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine,Hubei University of Chinese Medicine,Wuhan 430065,China;Xinjiang Uygur Pharmaceutical Co.,Ltd,Urumchi 830026,China)

机构地区：[1]湖北中医药大学湖北省中药资源与中药化学重点实验室,武汉430065 [2]新疆维吾尔药业有限责任公司,乌鲁木齐830026

出　　处：《世界科学技术-中医药现代化》2022年第3期1103-1112,共10页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：湖北省科学技术厅湖北省技术创新专项(2018AFB210):愈肝龙抗肝纤维化作用机制研究,负责人:尤朋涛。

摘　　要：目的研究护肝布祖热颗粒治疗刀豆蛋白A(Concanavalin A,ConA)诱导的小鼠急性免疫性肝损伤的作用机制。方法对小鼠尾静脉注射ConA(20 mg·kg^(-1))诱导免疫性肝损伤。小鼠随机分空白组、模型组、1.6 g·kg^(-1)和3.2 g·kg^(-1)护肝布祖热颗粒治疗组、泼尼松龙治疗组。灌胃给药10天,第11天注射ConA,4h后取肝脏组织,苏木精-伊红(H&E)染色观察肝脏病理学变化,采用DCFH-DA探针检测活性氧(ROS)水平。免疫组织化学法测定磷酸化c-Jun氨基末端激酶(p-JNK)的表达。TUNEL(TdT-mediated dUTP NickEnd Labeling)染色检测肝脏细胞凋亡情况。Western blot测定Bax、Bcl-2的表达。结果经检测发现,ConA造模后的小鼠肝脏出现大量肝细胞死亡和肝脏结构损伤。与模型组相比,1.6 g·kg^(-1)和3.2 g·kg^(-1)护肝布祖热颗粒治疗组ROS表达明显降低;肝脏内p-JNK的表达得到明显下降;肝细胞凋亡得到显著改善。结论以上结果表明护肝布祖热颗粒减轻小鼠免疫性肝损伤的机制为抑制ROS的产生,从而减少JNK激活引起的细胞凋亡。Objective To study the mechanism of Hugan Buzure granule in the treatment of acute immune liver injury induced by concanavalin A(ConA) in mice.Methods Immune liver injury was induced by injecting ConA(20 mg·kg^(-1))into the tail vein of mice. Mice were randomly divided into control group, model group, 1.6 g·kg^(-1)and 3.2 g·kg^(-1)Hugan Buzure granule group, and 6 mg·kg^(-1)prednisone group. In the drug treatment group, the mice were given intragastric administration for 10 days, and ConA was injected at the 11thday. Liver tissues were taken from all mice at 4 h after ConA injection, and the liver pathological changes were observed by hematoxylin-eosin(HE) staining. The level of reactive oxygen species(ROS) was detected using DCFH-DA probes. The expression of phosphorylated c-Jun amino terminal kinase(p-JNK) was assessed by immunohistochemistry. TUNEL(TdT-mediated dUTP Nick-End Labeling)staining was used to detect liver cell apoptosis. Western blot method was used to determine the expression of Bax, Bcl-2.Results It was found that a large number of liver cell deaths and liver structural damage occurred in the livers of mice modeled with ConA. Compared with the model group, the ROS expression in the 1.6 g·kg^(-1)and 3.2 g·kg^(-1)Hugan Buzure granule group was significantly reduced;the expression of p-JNK in the liver was markedly reduced;and the apoptosis of liver cells was significantly decreased.Conclusion The above results show that the mechanism of Hugan Buzure granule in reducing immune liver injury in mice is to inhibit the production of ROS and reduce the apoptosis caused by JNK activation.

关 键 词：护肝布祖热颗粒 免疫性肝损伤 氧化应激 凋亡 P-JNK 

分 类 号：R185.5[医药卫生—流行病学]