疏肝化瘀益气法对肝纤维化大鼠HIF-1α、VEGF表达的影响Effect of Methods of Smoothing Liver,Resolving Stasis and Tonifying Qi on the Expression of HIF-1α and VEGF in Hepatic Fibrosis Rats
张禹,黄秋思,刘定,杨沈秋
摘要(Abstract):
目的研究疏肝化瘀益气法干预肝纤维化大鼠模型过程中,对大鼠肝脏组织HIF-1α、VEGF表达的影响。方法采用无菌猪血清诱导大鼠肝纤维化模型。随机分为3组。空白组、模型组给予生理盐水灌胃;软肝散干预组自造模开始即给予软肝散生药水煎剂灌胃。采用HE染色和Masson染色观察肝组织纤维化程度,RT-PCR、Western bolt检测肝组织中HIF-1α、VEGF蛋白的表达情况。结果与模型组相比,软肝散干预组肝组织中HIF-1α、VEGF表达显著下调(P<0.05或P<0.01)。且随着干预给药时间的延长,其表达量逐渐降低。结论以疏肝化瘀益气法为指导的软肝散可以改善肝纤维化的病理改变,通过下调HIF-1α、VEGF表达,抑制HIF-1α、VEGF的过表达,调控HIF-1α/VEGF信号通路抑制肝组织纤维化进程,从而发挥抗纤维化的作用。
关键词(KeyWords): 疏肝化瘀益气法;软肝散;肝纤维化;缺氧诱导因子-1α;血管内皮生长因子;大鼠
基金项目(Foundation): 哈尔滨市科技创新人才研究专项资金(青年后备人才公益类)项目(2017RAQXJ187);; 黑龙江中医药大学附属第二医院科研青年基金(YQ-201704)
作者(Author): 张禹,黄秋思,刘定,杨沈秋
DOI: 10.13463/j.cnki.jlzyy.2020.02.027
参考文献(References):
- [1]汪美凤,平键,成扬.肝星状细胞主要信号转导通路与肝纤维化的关系[J].实用肝脏病杂志,2010,13(6):466-469.
- [2]BATALLER R,BRENNER D A.Liver fibrosis[J].Journal of Clinical Investigation,2005,115(2):209-218.
- [3]XU B,LIN L,XU G,et al.Long-term lamivudine treatment achieves regression of advanced liver fibrosis/cirrhosis in patients with chronic hepatitis B[J].Journal of Gastroenterology and Hepatology,2015,30(2):3 72-378.
- [4]ZIMMERMANN H W,TACKE F.In search of the magic bullet:can liver inflammation and fibrosis be reversed with medications?[J].Expert Review of Gastroenterology&Hepatology,2015,9(9):1139-1141.
- [5]陈永鹏,汪艳,侯金林,等.肝纤维化/肝硬化的动态变化及其诊断进展[J].中华肝脏病杂志,2015,23(4):244-246.
- [6]FELIX S.GRUNEWALD,PROTA A E,GIESE A,et al.Structure-function analysis of VEGF receptor activation and the role of coreceptors in angiogenic signaling[J].Biochimica et Biophysica Acta,2010,1804(3):567-580.
- [7]XU B,BROOME U,UZUNEL M,et al.Capillarization of Hepatic Sinusoid by Liver Endothelial Cell-Reactive Auto antibodies in Patients with Cirrhosis and Chronic Hepatitis[J].American Journal of Pathology,2003,163(4):1275-1289.
- [8]WARREN A,BERTOLINO P,BENSELER V,et al.Marked changes of the hepatic sinusoid in a transgenic mouse model of acute immune-mediated hepatitis[J].Journal of Hepatology,2007,46(2):239-246.
- [9]徐敏,聂时南.低氧诱导因子1在缺氧性疾病中的作用研究[J].临床急诊杂志,2014,15(9):564-567.
- [10]LUCZAK M W,ROSZAK A,PAWLIK P,et al.Increased expression of HIF-1A and its implication in the hypoxia pathway in primary advanced uterine cervical carcinoma[J].Oncol Rep,2011,26(5):1259-1264.
- [11]ROSENBERGER P,SCHWAB J M,MIRAKAJ V,et al.Hypoxia-inducible factor-dependent induction of netrin-1dampens inflammation caused by hypoxia[J].Nat Immunol,2009,10(2):195-202.
- [12]周丹,张立婷,李俊峰,等.缺氧诱导因子1α在肝纤维化发生发展中的作用机制[J].临床肝胆病杂志,2019,35(7):1604-1607.
- [13]夏雪皎,林庚庭,滕飞,等.疏肝健脾活血方对肝纤维化大鼠肝组织HIF-1α蛋白及VEGF mRNA表达的影响[J].中华中医药杂志,2018,33(4):1357-1360.
- [14]王翼天,邸莎,逄冰.诸脏纤化久病久痛皆属于络:仝小林教授从络论治脏器纤维化[J].吉林中医药,2018,38(5):520-523.
- [15]刘成海,赵志敏,吕靖.中医对肝纤维化逆转的认识与治疗[J].临床肝胆病杂志,2019,35(4):728-733.
- [16]张晔,吕金朋,孙佳明,等.鳖甲抗肝纤维化研究进展[J].吉林中医药,2018,38(6):673-675.
- [17]曹媛,夏延哲,陈杰,等.五味子甲素在人肝星状细胞中的抗纤维化作用[J].中国临床药理学与治疗学,2016,21(8):878-883.
- [18]王学良,卢秉久.软肝冲剂对四氯化碳所致小鼠肝纤维化模型的影响[J].长春中医药大学学报,2015,31(5):911.
- [19]杨沈秋,孙忠人,刘定,等.张金良主任医师治疗酒精性肝纤维化经验[J].世界最新医学信息文摘,2015,15(32):252-253.
- [20]杨沈秋,张禹,潘祥宾.“组药”汤方治疗脾虚血疲型臌胀20例临床观察[J].中国中医药科技,2011,18(5):413.