Clinical Study of Dahuang Zhechong Pill (大黄■虫丸) in Treating Posthepatitis B Hepatic Fibrosis

Hepatic fibrosis is the only way for all kinds of chronic hepatic diseases to develop into liver cirrhosis. How to block and reverse hepatic fibrosis is the key issue for treatment of all kinds of chronic hepatic disease. After many years’ arduous effort in treating hepatic fibrosis, no satisfactory results in western medical treatment have been obtained. Though hepatic fibrosis could be definitely re-

Clinical antitumor application and pharmacological mechanisms of Dahuang Zhechong Pill

Cancer still has elevated morbidity and mortality,which undoubtedly impacts the life quality of affected individuals.Remarkable advances have been made in cancer therapy,although the toxicities of traditional therapies remain an obvious challenge.Dahuang Zhechong Pill(DHZCP),developed by Zhongjing Zhang in the Synopsis of the Golden Chamber,represents an effective anticancer traditional Chinese medicine(TCM).In this review,it was found that DHZCP is therapeutically utilized in liver,lung,gastric,pancreatic and other cancers in clinic.Pharmacological evidence showed that its anti-tumor mechanisms mainly involve induced cell cycle arrest,apoptosis and autophagy,as well as suppressed tumor cell proliferation,obstructed angiogenesis and metastasis,enhanced immunity,and reversal of multidrug resistance.The present review provides a solid basis for the clinical application of DHZCP and may promote the wide use of TCM in clinical antitumor application.

Dahuang Zhechong pills inhibit liver cancer growth in a mouse model by reversing Treg/Th1 balance

The infiltration of immune cells into the hepatocellular carcinoma microenvironment is the main reason why hepatocellular carcinoma patients are prone to carcinoma recurrence and the disease are incurable.Notably,the infiltration of Treg cells is the main trigger.Dahuang Zhechong pill(DHZCP)is a traditional Chinese herbal compound successful in the treatment of hepatitis and hepatocellular carcinoma.DHZCP can heal and nourish while slowing the onset of the disease,thereby strengthening the body’s immune function.It can localize tumors and ultimately achieve the goal of eliminating tumors.In this study,an orthotopic liver cancer model of mice was used to explore the mechanism of DHZCP enhancing anti-tumor immunity,which showed more Th1 cells in the peripheral blood and spleen after DHZCP treatment,while more IFN-γwas secreted to activate CD8^(+)T cells and Treg cell production was inhibited,thereby suppressing the growth of HCC.Finally,we also analyzed the potential components of DHZCP from the perspective of modern targets using network pharmacology methods and experimental results.

Effects and Mechanisms of the Functional Parts of Dahuang Zhechong Pill(大黄虫丸) Containing Serum on Platelet-Derived Growth Factor-Stimulated Proliferation of Vascular Smooth Muscle Cells

Objective： To investigate and compare the effects and mechanisms of three functional parts of Dahuang Zhechong Pill （大黄〈庶虫〉虫丸, DHZCP）, including drugs with the function of removing blood stasis and promoting blood circulation （FP- I ）, drugs with the function of expelling heat and moistening dryness （FP-II）, and drugs with the function of nourishing yin and replenishing blood （FP-m） of DHZCP, on platelet-derived growth factor （PDGF）-stimulated vascular smooth muscle cells （VSMCs） proliferation with the method of serum pharmacology. Methods： VSMCs proliferation of rat was assayed by measuring the cell viability with the 3-（4, 5-dimethylthiazol-2yl）-2, 5-diphenyltetrazolium bromide （Ml-I＇） method. DNA synthesis in VSMCs was examined by detecting 5＇-bromo-2＇-deoxyuridine incorporation with the immunocytochemical method. Cycle of VSMCs was evaluated with flow cytometry. Expression of cyclin D1, p27, PKC a, and phosphorylated extracollular signal regulated kinase 1/2 （ERK1/2） was quantified by the Western blotting method. Results： The FP- I and FP-m containing serum was capable of inhibiting PDGF-stimulated proliferation and DNA synthesis of VSMCs, arrested VSMCs in G1 phase, downregulated cycUn D1, and upregulated p27 expression （P〈0.01 or P〈0.05）. The FP- I and FP-11I containing serum also inhibited the PDGF-induced phosphorylation of tyrosine of ERK1/2 and PKCo~ expression （P〈0.01 or P〈0.05）. Conclusions： FP- I and FP-$ of DHZCP are able to inhibit VSMCs proliferation via interrupting PKC a-ERK1/2 signaling, modulating the expression of cell cycle proteins to result in arresting the cells in G1 phase. The inhibitory effect is mainly related to the function of removing blood stasis and promoting blood circulation, slightly to the function of nourishing yin and replenishing blood, but not to the function of expelling heat and moistening dryness.

Dahuang Zhechong Pill(大黄虫丸) Containing Serum Inhibited Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells Proliferation by Inducing G_1 Arrest Partly via Suppressing Protein Kinase C α-Extracellular Regulated Kinase 1/2 Signaling

Objective： To investigate effects of Dahuang Zhechong Pill （大黄庶虫丸, DHZCP） on the cell cycle and the related signal pathways in vascular smooth muscle cells （VSMCs） stimulated by platelet-derived growth factor （PDGF） with the method of serum pharmacology. Methods： DNA synthesis in VSMCs was examined by detecting 5＇-bromo-2＇-deoxyuridine incorporation with the immunocytochemical method. The cycle of VSMCs was evaluated with flow cytometry. Expressions of cyclin D1, p27, protein kinase C α （PKC α）, and phosphorylated extracellular signal regulated kinase 1/2 （ERK1/2） were quantified by Western blot method. Results： DHZCP containing serum significantly inhibited DNA synthesis of PDGF-stimulated VSMCs, arrested the cells in G1 phase, modulated the protein expressions of cyclin D1 and p27, and suppressed the activation of PKC α and ERK1/2. Conclusion： DHZCP containing serum inhibits VSMCs proliferation via modulating the expressions of cell cycle proteins to arrest the cell in G1 phase, which is attributed to, at least in part, suppressing PKC α -ERK1/2 signaling in VSMCs.

An experimental study of a modified Dahuang Zhechong pill on theangiogenesis of RF/6A cells in vitro

OBJECTIVE:To investigate the effects of a modified Dahuang Zhechong Pill(MDZP) on the angiogene sis of rhesus choroid-retina endothelial(RF/6A cells and its preliminary mechanism.METHODS:A 3-(4,5-dimethylthiazol-2-yl)-5-(3-car boxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazol ium(MTS) method was used to assess the effect o a MDZP on RF/6A cell proliferation induced by vas cular endothelial growth factor(VEGF).Transwell in serts were used to assess the effect of the MDZP on RF/6A cell migration.Matrigel was used to asses the effect of the MDZP on the tube formation of RF 6A cells.Western blotting and quantitative re al-time reverse transcription polymerase chain reac tion(RT-PCR) were used to detect the protein and mRNA expression,respectively,of VEGF and matri metalloproteinase-2(MMP-2) in RF/6A cells treatedwith the MDZP.RESULTS:RF/6A cell proliferation induced by VEGF was inhibited by 0.2 mg/mL MDZP.At 0,12.5,25 and 50 mg/mL MDZP,the number of cells that migrated through Transwell membranes was 73.33± 4.51,61.33±4.04,28.67±6.66 and 17.67±4.16,respectively,and the number of tubes formed in Matrigel was 20.33±0.58,13.33±1.53,11.00±1.00 and 1.33±0.58,respectively.At 100 and 200 mg/mL MDZP,the protein and mRNA expression of VEGF and MMP-2 were inhibited in RF/6A cells.At 400 mg/mL MDZP,the expression of VEGF mRNA and MMP-2 protein were inhibited in RF/6A cells.CONCLUSIONS:MDZP inhibits the angiogenesis of RF/6A cells via the suppression of proliferation,migration and tube formation of RF/6A cells.Inhibition of the protein and mRNA expression of VEGF and MMP-2 in RF/6A cells may be an important mechanism.

大黄[庶虫]虫丸治疗肝癌的研究进展

大黄[庶虫]虫丸出自《金匮要略》,是治疗“虚劳干血”类疾病的经典名方,近年来广泛用于多种恶性肿瘤尤其是肝癌的综合治疗中。检索整理近20年文献,从中医组方特色、临床应用、分子机制三方面总结大黄[庶虫]虫丸治疗肝癌的相关研究,发现大黄[庶虫]虫丸在中医组方上具有虫类逐瘀、草本养虚,肝脾同调、两脏兼顾,蜜丸为剂、峻药缓图等特色,配伍严谨,用药精当。在临床上无论是联合经动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)还是联合静脉化疗,均可减轻治疗不良反应,提高临床有效率,延长患者生存时间;此外,对于晚期原发性肝癌患者以及肝转移癌患者,单药应用也可明显改善症状,提高生活质量,延长终末期患者带瘤生存时间,临床疗效确切,且可长期应用,安全性较高。机制研究中发现大黄[庶虫]虫丸具有抗肝癌前病变、保护肝细胞,调节肝功能,抗肝癌细胞转移、抑制肿瘤血管新生,促进血管正常化、调节免疫等相关机制,分子机制明确。通过以上三方面,全面详细阐述了大黄[庶虫]虫丸治疗肝癌的研究现状,并对目前的临床和实验研究提出不足与改进,以期为后续深入研究及抗肿瘤新药的研发提供思路和依据。

逍遥散合大黄[庶虫]虫丸治疗原发性肝癌经肝动脉化疗栓塞术后气滞血瘀型疗效研究

目的:研究逍遥散合大黄[庶虫]虫丸对经肝动脉化疗栓塞(TACE)术后的原发性肝癌(PLC)患者气滞血瘀型的治疗效果。方法:将80例肝癌气滞血瘀型患者采用随机数字表法分为观察组和对照组各40例。对照组肝癌患者TACE术后予对症治疗,观察组肝癌患者在对症治疗的基础上联合逍遥散合大黄[庶虫]虫丸进行治疗。经治疗1个月后复查肝功能、凝血功能、肿瘤指标及上腹部影像学检查的变化情况。结果:观察组血清甲胎蛋白(AFP)、糖类抗原199(CA199)、糖类抗原125(CA125)等肿瘤指标,谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)、总蛋白(TP)、白蛋白(ALB)等肝功能指标,凝血酶原时间(PT)、凝血酶原活动度(PTA)、国际标准化比值(INR)、纤维蛋白原(FIB)等凝血功能指标低于对照组,差异具有统计学意义(P<0.05),观察组总有效率75.00%,获益率90.00%,对照组总有效率32.50%,获益率57.50%,观察组总有效率高于对照组(P<0.05)。结论:肝癌气滞血瘀型患者在经过TACE术后,在对症治疗的基础上加用中药内服方逍遥散合大黄[庶虫]虫丸具有更好的疗效,逍遥散合大黄[庶虫]虫丸可以加强对肝功能的保护,有效地改善凝血功能,降低肝癌的转移程度。

大黄廑虫丸联合抗病毒治疗乙型肝炎肝硬化对凝血功能紊乱、肝硬化程度及门静脉系统相关参数的影响

目的探讨大黄廑虫丸联合抗病毒治疗乙型肝炎(HBV)肝硬化对病人凝血功能紊乱、肝硬化程度及门静脉系统相关参数的影响。方法选择2020年6月至2022年6月于无锡市中医医院接受治疗的100例HBV肝硬化病人,运用随机数字表法将其分为观察组与对照组,各50例。对照组采用常规抗病毒疗法,观察组基于对照组联合大黄廑虫丸,评估两组疗效并进行比较,对比两组凝血功能、HBV-DNA值、肝硬化程度、门静脉系统相关参数变化。结果观察组治疗显效病人占50.00%高于对照组26.00%,差异有统计学意义(P<0.05);治疗前两组病人的血小板计数(PLT)、凝血酶时间(TT)、纤维蛋白原(FIB)、HBVDNA水平比较差异无统计学意义(P>0.05),治疗后PLT[(125.42±24.57)×10^(9)/L比(116.12±21.38)×10^(9)/L]、FIB水平[(2.76±0.56)g/L比(1.80±0.63)g/L]高于对照组,TT[(14.18±4.28)s比(16.61±5.34)s]、HBV-DNA[(2.72±0.43)×10^(5) IU/L比(3.38±0.68)×10^(5) IU/L]小于对照组,差异有统计学意义(P<0.05);两组治疗前后的肝硬化程度和门静脉内径比较差异无统计学意义(P>0.05),治疗后观察组肝脏硬度数值(LSM)(15.32±2.27)kPa比(17.94±2.34)kPa、肝门静脉内径[(12.29±1.98)mm比(13.80±2.15)mm]低于对照组,差异有统计学意义(P<0.05);两组治疗前天冬氨酸氨基转移酶(AST)、丙氨酰氨基转移酶(ALT)水平比较差异无统计学意义(P>0.05),治疗后ALT、AST水平均下降,观察组下降幅度高于对照组,差异有统计学意义(P<0.05)。结论相较于单独抗病毒治疗,联合大黄廑虫丸治疗,疗效较好,改善肝功能,有助于凝血功能的恢复,缩小肝门静脉内径。

张仲景“缓中补虚”之浅谈

目的:浅论“缓中补虚”内涵,探讨张仲景临床思维。方法:对张仲景《金匮要略》中大黄?虫丸条文及药味进行研究,加以现代“缓中补虚”治法相关临床文献进行补充。结论:“缓中补虚”作为虚劳干血的治则,其中“缓”为干血攻伐药味处方的核心法则,“补虚”为其目的,代表方大黄?虫丸现代应用广泛,提示张仲景临床思维至今在现代医疗体系中仍具有指导意义。

基于“异病同治”理论研究大黄䗪虫丸抑制心、肺纤维化生物学基础

目的:基于“异病同治”理论探讨大黄䗪虫丸(DHZCP)含药血清对肺纤维化和心肌纤维化体外模型的治疗作用及共同生物分子学机制。方法:以小鼠肺泡巨噬细胞MH-S细胞系和大鼠心肌细胞H9C2细胞系为研究对象。两种细胞均分别设4组:空白对照组、模型对照组、DHZCP组和TGF-β1特异性受体激酶抑制剂TRKI(SB-431542)组。除空白对照组外,采用SiO_(2)(50μg/cm~2)诱导肺纤维化体外模型,脂多糖(LPS,1μg/mL)诱导心肌纤维化细胞模型,DHZCP(15%)和抑制剂SB-431542(3.8μg/mL)处理后,CCK-8检测细胞活性,RT-PCR法检测各组中TGF-β1、α-SMA、Smad2、Smad3、Smad7基因的mRNA表达水平,WB检测各组中TGF-β1、α-SMA、Smad2、Smad3、Smad7蛋白的表达水平,免疫荧光检测上述蛋白的定位表达。结果:MH-S细胞系结果可见,与空白对照组相比,模型对照组的细胞活力下降,TGF-β1、α-SMA、Smad2和Smad3的mRNA和蛋白均升高,而Smad7的mRNA和蛋白均降低。给药干预后,与模型对照组相比,各受试药物组的细胞活力均提升,TGF-β1、α-SMA、Smad2和Smad3的mRNA和蛋白均降低,Smad7的mRNA和蛋白均上升。H9C2细胞系结果可见,模型对照组较空白对照组的细胞活力亦下降,TGF-β1、α-SMA、Smad2和Smad3的mRNA和蛋白均上升,而Smad7的mRNA和蛋白均下调。与模型对照组相比,给药干预组的细胞活力均上升,TGF-β1、α-SMA、Smad2和Smad3的mRNA和蛋白均降低,Smad7的mRNA和蛋白均上调,差异均有统计学意义。结论:DHZCP能提高MH-S和H9C2两种细胞的活性,抑制α-SMA、TGF-β1、Smad2、Smad3表达,升高Smad7表达,表明DHZCP对肺和心肌纤维化的抑制作用与调节TGF-β1/Smad信号通路有关,这也是二者“异病同治”的生物分子学基础。

基于网络药理学研究大黄蛰虫丸抗肝癌增殖的机制

目的 用网络药理学方法系统筛选大黄蛰虫丸治疗肝癌的药物成分、作用靶点及相关信号通路,揭示其抗肝癌增殖的作用机制。方法 用TCMSP、Genecards、TTD、Disgenet、OMIM数据库及相关文献筛选大黄蛰虫丸药靶基因与肝癌疾病基因的共有基因,构建“活性成分-靶点-通路图”,将共有基因导入STRING数据库构建PPI网络,并通过DAVID数据库进行通路富集分析。结果 大黄蛰虫丸共有198个活性成分,其中槲皮素、芍药苷、黄芩素及漆酚等可能是治疗肝癌的潜在物质基础,通过蛋白互作网络得到丝氨酸/苏氨酸蛋白激酶1(serine-threonine kinase 1, AKT1)、肿瘤蛋白P53(tumor protein P53, TP53)、丝裂原活化蛋白(mitogen-activated protein kinase, MAPK1)、信号转导和转录激活因子(signal transducer and activator of transcription 3, STAT3)、转录因子(transcription factor AP-1, JUN)、酪氨酸蛋白激酶(tyrosine-protein kinase, SRC)等核心靶点。富集通路涉及癌症、PI3K-AKT、MAPK、乙型肝炎、小细胞肺癌等通路。结论 该研究提示大黄蛰虫丸能够通过抑制PI3K-AKT信号通路诱导肝癌细胞凋亡,为大黄蛰虫丸治疗肝癌提供科学依据。

UPLC-MS/MS测定大黄蛰虫丸中的9种成分

目的建立超高效液相色谱-串联质谱(UPLC-MS/MS)同时测定大黄蛰虫丸中黄芩素、黄芩苷、苦杏仁苷、大黄酚、大黄素甲醚、甘草苷、芍药苷、毛蕊花糖苷、甘草酸铵含量的分析方法。方法采用Agilent Technologies Infinity Lab Poroshell 120 EC-C18(4.6 mm×100 mm,2.7μm)色谱柱,以乙腈-0.1%甲酸水溶液为流动相,梯度洗脱,流速0.3 ml/min;电喷雾离子源正负同时检测,多反应监测(MRM)扫描模式,通过比较供试品与对照品的色谱保留时间、色谱峰面积,同时进行黄芩素、黄芩苷、苦杏仁苷、大黄酚、大黄素甲醚、甘草苷、芍药苷、毛蕊花糖苷、甘草酸铵的定量测定。结果9种成分线性范围的相关系数(r)均不低于0.998,回收率为93.77%~101.27%,RSD为0.57%~1.79%。结论该法快速简便、高通量、选择性好、灵敏度高,能为大黄蛰虫丸的质量控制提供依据。

基于网络药理学的大黄蛰虫丸治疗结直肠癌作用机制研究

目的:探讨大黄蛰虫丸治疗结直肠癌的药效物质基础以及作用机理。方法:利用TCMSP、TCMID系统并通过文献研究,以获得大黄蛰虫丸的主要化学成份及其功效靶位。再根据GeneCards中的结直肠癌药物靶位、DrugBank中的结直肠癌阳性药功能靶位相结合,证明大黄蛰虫丸功效靶位与结直肠癌之间的相互作用。借助Cytoscape3.7.1软件构建“组分-靶点”网络模型。最后,借助DAVID将主要靶点映射KEGG通路上,进一步阐释主要靶点与大黄蛰虫丸治疗结直肠癌的潜在联系。结果:“组分-靶点”网络包含226个化学组分和相应靶点34个(其中关键药效组分7个,主要靶点26个),主要靶点涉及NOS2、PPARG、PIK3CG、F2、GSK3B、CDK2、PGR、CHEK1等。映射KEGG通路111条(P<0.05),涉及的通路有PI3K-Akt通路、TNF通路、VEGF通路等。结论:结合文献和预测结果分析,榭皮素、L-尿苷为大黄蛰虫丸发挥抗结直肠癌作用的关键药效分子,其机制可能与PI3K-Akt信号通路有关。

大黄䗪虫丸联合恩替卡韦抗乙型肝炎性肝纤维化疗效的Meta分析

目的:应用Meta分析评价大黄䗪虫丸联合恩替卡韦治疗乙型肝炎性肝纤维化的临床疗效、应用价值及研究方向。方法:检索数据库包括知网(CNKI)、万方(WANFANG)、维普(VIP)、中国生物医学数据库(CBM)、PubMed、The Cochrane Library、Embase。检索时间范围系自建库至2022年9月。挑选出大黄䗪虫丸联合恩替卡韦治疗乙型肝炎肝纤维化的随机对照试验(RCT),应用RevMan 5.3分析软件分析。结果:文献筛选结果显示,共有8个研究被纳入,包含690例患者,观察组和对照组各有347例和343例。Meta分析结果显示,大黄䗪虫和恩替卡韦两药联用组对于乙型肝炎性肝纤维化患者血清中透明质酸(HA)、层黏蛋白(LN)、Ⅲ型胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)的改善效果优于单用恩替卡韦的对照组,除了Ⅳ型胶原(Ⅳ-C),其他三项标志物两组间差异均达到统计学显著性。结论:结果显示,大黄䗪虫丸联合恩替卡韦有良好的抗乙型肝炎性肝纤维化作用,表明大黄䗪虫丸具有抗乙型肝炎性肝纤维化作用或增强恩替卡韦抗乙型肝炎性肝纤维化作用,提示临床治疗乙型肝炎性肝纤维化时可考虑选用大黄䗪虫丸和恩替卡韦联合使用的治疗方案。

大黄蟅虫丸抗大鼠免疫性肝纤维化研究

目的：研究大黄虫丸防治肝纤维化的作用。方法：运用大鼠免疫性肝纤维化模型，观察大黄虫丸对肝组织病理学、肝羟脯氨酸（ＨＹＰ）含量的影响。结果：大黄虫丸预防和治疗试验肝纤维化率分别为７２．７％和７１．２％，而模型组和秋水仙碱组肝纤维化率为９２．３％～１００％，尤其是大黄虫丸治疗试验组肝ＨＹＰ含量下降显著，与模型组比较Ｐ＜０．０５。结论：大黄虫丸有一定的抗肝纤维化作用。

大黄蛰虫丸对动脉粥样硬化模型大鼠内皮功能的影响

目的观察大黄蛰虫丸对血脂、内皮素、内皮舒张因子在动脉粥样硬化（AS）模型大鼠中表达的影响。方法 SD雄性大鼠体重220~300 g,随机分为5组,对照组、模型组、大黄蛰虫丸高剂量组、低剂量组,阳性药组,每组8只,共40只。用高脂饲料喂养,建立大鼠AS模型,用大黄蛰虫丸灌胃12 w后,观察各组大鼠血清血脂,内皮素（ET）,一氧化氮（NO）含量的变化。结果模型组ET含量显著升高,NO含量显著降低,与对照组比较有显著差异（P〈0.05）,大黄蛰虫丸组较模型组血清ET含量明显降低,NO含量显著升高（P〈0.05）。结论大黄蛰虫丸通过降低血清ET含量,升高血清NO,保护内皮功能,发挥抗AS的作用。

大黄虫丸对阿霉素肾病大鼠足细胞骨架蛋白desmin影响的实验研究

目的:探讨大黄虫丸对阿霉素肾病大鼠足细胞损伤的保护作用。方法:SD大鼠一次性尾静脉注射阿霉素5 mg/kg,随机分为模型组和大黄虫丸组,另以8只正常大鼠作为对照组,进行对比观察。于实验第7日、14日,各处死4只模型组大鼠,留取肾脏标本待测。实验第28日,大鼠测尿蛋白后,全部处死,观察大鼠肾组织病理形态学变化及超微结构的改变,应用免疫荧光方法定位及半定量分析研究足细胞损伤标志蛋白-desmin的表达变化。结果:与正常对照组比较,阿霉素肾病大鼠肾小球内desmin蛋白表达上调,足细胞部分足突融合,尿白蛋白排泄率增高。结论:大黄虫丸可明显减轻阿霉素肾病大鼠肾小球内desmin蛋白的表达,减轻足细胞足突融合,降低尿白蛋白排泄率。大黄虫丸对阿霉素肾病大鼠的足细胞损害有一定的保护作用。

大黄蟅虫胶囊联合恩替卡韦治疗慢性乙型肝炎肝纤维化的效果观察

目的观察大黄蟅虫胶囊联合恩替卡韦治疗慢性乙型肝炎肝纤维化的临床疗效。方法收集2014年10月-2016年1月于北京大学深圳医院门诊和住院治疗的慢性乙型肝炎肝纤维化患者100例。将患者随机分为2组,每组各50例,其中西药组采用恩替卡韦治疗,联合治疗组在西药组的基础上加服大黄蟅虫胶囊治疗,疗程均为48周。观察两组患者肝功能、HBV DNA载量、血清肝纤维化4项、肝脏硬度、天门冬氨酸氨基转移酶-血小板指数(APRI)/肝纤维化指数(Fibro Index)变化情况。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验。结果与同组治疗前相比,治疗48周后两组患者肝功能ALT、AST和HBV DNA载量均下降,差异均有统计学意义(P值均<0.05)。两组患者治疗后肝纤纤维化4项均恢复正常,且两组间血清透明质酸、Ⅲ型前胶原、Ⅳ型胶原水平比较,差异均有统计学意义(P值均<0.05)。治疗后两组间比较,门静脉内径、脾厚度、肝硬度值和APRI/FibroIndex指数。差异均有统计学意义(P值均<0.05)。联合治疗组治疗总有效率(92.0%)高于西药组(72.0%),差异有统计学意义(χ2=6.775,P=0.009)。结论大黄蟅虫胶囊联合恩替卡韦治疗慢性乙型肝炎肝纤维化疗效优于单用恩替卡韦。

大黄虫丸对大鼠肝星状细胞表达TGF-β_1的影响

目的 :探讨大黄虫丸对大鼠肝星状细胞表达转化生长因子β1(TGF β1)的影响。方法 :用CCl4复合因素致大鼠肝纤维化模型 ,同时分别给予 3种剂量大黄虫丸治疗 ,免疫组化方法观察TGF β1、α 平滑肌肌动蛋白 (α SMA)的合成表达及纤维化程度分级。结果 :经给予大黄虫丸干预治疗常规剂量组大鼠TGF β1、α SMA表达与模型组比较差异无显著性 (P >0 0 5 ) ,但双倍剂量组和三倍剂量组TGF β1、α SMA在汇管区及不连续纤维间隔的表达明显减弱 (P <0 0 5 ,P <0 0 1)。结论 :大黄虫丸较大剂量能抑制肝星状细胞增殖和分泌TGF β1,减少胶原生成 ,从而减弱肝星状细胞的自分泌放大效应 ,这可能是大黄虫丸抗肝纤维化作用的主要机制之一。