摘要
目的研究鹿茸多肽(Velvet Antler Polypeptides,VAP)对四氯化碳(CCl4)诱导的小鼠肝纤维化的保护作用及其机制。方法采用腹腔注射四氯化碳法诱导小鼠肝纤维化动物模型。将小鼠随机分为正常组、四氯化碳组、四氯化碳+鹿茸多肽组(20、40 mg·kg^(-1))、阳性对照组(水飞蓟宾组,SB,100 mg·kg^(-1))。各组动物每天给予相应剂量药物灌胃,连续干预6周。采用HE染色法观察病理组织形态;采用ELISA法检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)及炎症因子(TNF-α、IL-1β、IL-6)的含量;采用免疫组化法检测肝纤维化标志物(α-SMA,Col-I)的蛋白表达水平;采用Western Blot法检测肝脏MAPK和PI3K/Akt信号蛋白表达。结果与正常组比较,模型组小鼠肝脏出现大量脂肪变性和炎性浸润,肝脏纤维化标志物α-SMA、Col-I明显高表达,肝损伤指标ALT、AST水平均明显升高(P<0.01),促炎因子TNF-α、IL-1β、IL-6水平均明显升高(P<0.01)。与模型组比较,鹿茸多肽组能明显降低α-SMA、Col-I的表达水平,改善肝脏纤维化病理改变,降低ALT、AST、TNF-α、IL-1β、IL-6血清含量(P<0.01),并逆转肝脏MAPK和PI3K/Akt的信号蛋白表达水平。结论鹿茸多肽可能是通过干预MAPK和PI3K/Akt信号传导路径,从而实现对四氯化碳诱导的小鼠肝纤维化的保护作用。
Objective To study the protective effect of velvet antler polypeptide(VAP) on carbon tetrachlorideinduced liver fibrosis in mice and its mechanism.MethodsThe rat liver fibrosis model was induced byintraperitoneal injection of carbon tetrachloride. Mice were randomly divided into normal group,carbon tetrachloridegroup,carbon tetrachloride +VAP group(20,40 mg·kg^(-1))and positive control group(Silybin group,SB,100 mg·kg^(-1)).The animals in each group were given the corresponding dose of drugs daily by gavage,and the intervention wascontinued for 6 weeks. HE staining was applied to observe the pathological morphology. The serum levels of ALT,AST and pro-inflammatory cytokines(TNF-α, IL-1β, IL-6) were measured by ELISA. Immunohistochemical method was used to detect the protein expression level of liver fibrosis markers(α-SMA,Col-I). Western blot wasused to detect the expression of MAPK and PI3 K/Akt signal proteins in liver.ResultsCompared with the controlgroup,there was extensive steatosis and inflammatory infiltrates in the liver of the model group, the biomarkerslevel of α-SMA,Col-I,ALT,AST,TNF-α,IL-1β,IL-6 significantly increased(P<0.01);In the treatmentgroup, VAP significantly reduced the expression of liver fibrosis markers(α-SMA, Col-I) and improved thepathological changes of liver fibrosis. It was also found that the serum levels of liver injury indicators(ALT,AST)and pro-inflammatory factors(TNF-α, IL-1, IL-6) were decreased(P<0.01), and the signaling proteinexpression levels of MAPK and PI3 K/Akt in the liver were reversed.ConclusionVAP may protect liver fibrosis inmice induced by CCl4 via interfering MAPK and PI3 K/Akt signal transduction pathways.
作者
周霖
王肖辉
荆自伟
杜秋争
师莹莹
孙志
洪晋
赵杰
ZHOU Lin;WANG Xiaohui;JING Ziwei;DU Qiuzheng;SHI Yingying;SUN Zhi;HONG Jin;ZHAO Jie(Department of Pharmacy,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052 Henan,China;Henan Precision Medicine Clinical Mass Spectrometry Engineering Research Center,Zhengzhou 450052 Henan,China;Department of Ultrasonography,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052 Henan,China;Department of Cardiovascular Medicine,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052 Henan,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2021年第3期338-345,共8页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家重点研发计划“精准医学研究”重点专项(2017YFC0909900)
河南省科技攻关重点研发与推广专项(202102310191)
河南省高等学校重点科研项目基础研究计划(19A320070)
郑州市协同创新重大专项(郑州大学)项目(20XTZX08017)。
作者简介
周霖,男,主管药师,研究方向:中药药理。Email:fcczhoul@zzu.edu.cn;共同第一作者:王肖辉,女,主治医师,研究方向:中药药理。Email:fccwangxh2@zzu.edu.cn;通信作者:赵杰,男,主任药师,研究方向:医院药学,Email:zhaojie@zzu.edu.cn;通信作者:洪晋,女,主治医师,研究方向:中药药理。Email:xyhongjin@126.com。
