Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet

BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen.Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.AIM To explore baseline serum metabolites characteristics in responders.METHODS A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited.First,all subjects were divided into training set and validation set.Second,the included patients were subdivided into entecavir responders(E-R),entecavir no-responders(E-N),FZHY+entecavir responders(FR),and FZHY+entecavir no-responders(F-N)following the pathological histological changes after 48 wk’treatments.Then,Serum samples of all subjects before treatment were tested by high performance liquid chromatographytandem mass spectrometry(LC-MS)high-performance LC-MS.Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis.Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.RESULTS As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N,results showed that 4 pathways including linoleic acid metabolism,aminoacyl-tRNA biosynthesis,cyanoamino acid metabolism,alanine,aspartate and glutamate metabolism were screened out.As for the differential metabolites,these 7 intersected metabolites including hydroxypropionic acid,tyrosine,citric acid,taurochenodeoxycholic acid,benzoic acid,2-Furoic acid,and propionic acid were selected.CONCLUSION Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.

Effects of Fuzhenghuayu decoction on collagen synthesis of cultured hepatic stellate cells,hepatocytes and fibroblasts in rats

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Effect of Fuzhenghuayu decoction on vascular endothelial growth factor secretion in hepatic stellate cells

Objective: To investigate the effect of Fuzhenghuayu decoction on autocrine activation of hepatic stellate cell (HSC). Methods: The drug serum containing Fuzhenghuayu decoction was collected from normal rats, and cul- tured with activated HSC in vitro. The conditioned medium from the drug serum treated HSC was added to primary cultured quiescent HSC. Cell prolifera- tion was assayed by tetrazolium colorimetric test, and the contents of type Ⅰ collagen and vascular endo- thelial growth factor (VEGF) in the supernatant were measured with ELISA. Results: The conditioned medium from activated HSC could stimulate the quiescent HSC proliferation and type Ⅰ collagen secretion. The drug serum inhibi- ted this stimulating action and VEGF secretion from the activated HSC. Conclusion: Fuzhenghuayu decoction acts effectively against the autocrine activation pathway of HSC. The mechanism may be associated with the inhibition of the secretion of VEGF by activated HSC.

Network-pharmacological study of FuzhengHuayu formula againsts liver fibrosis

Aim Liver fibrosis is a consequence of chronic liver disease which can progress into liver cirrhosis evenhepatocarcinoma. FuzhengHuayu （FZHY） , a Chinese herbal formula, had been reported to have the effect of anti- fibrosis. This study aims to investigate the effective targets and the mechanisms of FZHY on liver fibrosis. Methods The liver tissue samples of normal group, model group and FZHY-treated group were examined by microarray and iTRAQ. Profiles of differentially expressed genes （DEGs） and differentially expressed proteins （DEPs） in CC14-in- duced liver fibrosis model in rat were analyzed. GO and Pathway were analyzed by DAVID, and protein-protein in- teraction （PPI） was analyzed by STRING and cytoscape. The targets of FZHY compounds were predicted by TCM- SP. Results The results showed that 255 genes （ fold change ≥ 1.5, P 〈 0.05） and 507 proteins （ fold change ≥ 1.2 ,P 〈 0.05 ） were differentially expressed between FZHY group and model group. The high-throughput data of transcriptomics and proteomics was analyzed synthetically. DAVID function annotation analysis showed that these DEGS and DEPs both enriched in 15 GO terms, among drug metabolic process, response to extracellular stimulus, response to vitamin, arachidonic acid metabolic process, response to wounding and oxidation reduction may involve in liver fibrosis. KEGG pathway analysis showed that these DEGS and DEPs both enriched in 9 pathways, among arachidonic acid metabolism, retinol metabolism, metabolism of xenobiotics by cytochrome P450 and drug metabo- lism may be related to liver fibrosis. PPI analysis found that 10 overlapped core genes and proteins, among, Ugt2a3, Cyp2bl and Cyp3al8 were of higher degree, which are all enriched in retinol metabolism. Interestedly, Cyp2bl and Cyp3al8 were also predicted with TCMSP as the targets of FZHY compounds. Conclusion The re- sults indicated that the effective mechanism of FZHY against liver fibrosis is involved in the regulation of multiple targets and multiple pathways, among, retinol metabolism pathway by targeting Ugt2a3, Cyp2bl and Cyp3al8 may play an important role in the treatment of liver fibrosis.

Multicenter clinical study on Fuzhenghuayu capsule against liver fibrosis due to chronic hepatitis B

AIM: To study the efficacy and safety of Fuzhenghuayu capsule (FZHY capsule, a capsule for strengthening body resistance to remove blood stasis) against liver fibrosis due to chronic hepatitis B. METHODS: Multicenter, randomized, double blinded and parallel control experiment was conducted in patients (aged from 18 to 65 years) with liver fibrosis due to chronic hepatitis B. Hepatic histologic changes and HBV markers were examined at wk 0 and 24 during treatment. Serologic parameters (HA, LM, P-Ⅲ-P, Ⅳ-C) were determined and B ultrasound examination of the spleen and liver was performed at wk 0, 12 and 24. Liver function (liver function and serologic parameters for liver fibrosis) was observedat wk 0, 6, 12, 18 and 24. Blood and urine routine test, renal function and ECG were examined before and after treatment. RESULTS: There was no significant difference between experimental group (110 cases) and control group (106 cases) in demographic features, vital signs, course of illness, history for drug anaphylaxis and previous therapy, liver function, serologic parameters for liver fibrosis, liver histologic examination (99 cases in experimental group, 96 cases in control group), HBV markers, and renal function. According to the criteria for liver fibrosis staging, meanscore of fibrotic stage(s) in experimental group after treatment (1.80) decreased significantly compared to the previous treatment (2.33, P＜0.05), but there was no significant difference in mean score of fibrotic stage(s) (2.11 and 2.14 respectively). There was a significant difference in reverse rate between experimental group (52%) and control group (23.3%) in liver biopsy. With marked effect on decreasing the mean value of inflammatory activity and score of inflammation (P＜0.05), Fuzhenghuayu capsule had rather good effects on inhibiting inflammatory activity and was superior to that of Heluoshugan capsule. Compared to that of pretreatment, there was a significant decrease in HA, LM, P-Ⅲ-P and Ⅳ-C content in experimental group after 12 and 24 wk of treatment. The difference in HA, LM, P-Ⅲ-P and Ⅳ-C content between 12 and 24 wk of treatment and pretreatment in experimental group was significantly greater than that in control group (P＜0.01-0.05). The effect, defined as two of four parameters lowering more than 30% of the baseline, was 72.7% in experimental group and 27.4% in control group (P＜0.01). Obvious improvement in serum Alb, ALT, AST and GGT was seen in two groups. Compared to that of control group, marked improvement in GGT and Alb was seen in experimental group (P＜0.05). The effective rate of improvement in serum ALT was 72.7% in experimental group and 59.4% in control group. No significant difference was seen in blood and urine routine and ECG before and after treatment. There was also no significant difference in stable rate in ALT and serologic parameters for liver fibrosis between experimental group and control group after 12 wk of withdrawal. CONCLUSION: Fuzhenghuayu capsule has good therapeutic effects on alleviating liver fibrosis due to chronic hepatitis B without any adverse effect and is superior to that of Heluoshugan capsule.

恩替卡韦联合扶正化瘀胶囊治疗乙型肝炎肝硬化疗效观察

目的观察恩替卡韦联合扶正化瘀胶囊治疗活动性肝硬化患者的疗效。方法 60例活动性乙型肝炎肝硬化患者被随机分为观察组30例和对照组30例,两组均给予常规治疗。给予对照组患者恩替卡韦片治疗24 w,给予观察组患者恩替卡韦联合扶正化瘀胶囊治疗,观察并比较两组血清肝纤维化指标和肝功能变化。结果治疗前对照组患者血清透明质酸为(320.4±196)ng/ml,层黏连蛋白为(180.9±80)ng/ml,Ⅲ型前胶胶原为(261.2±132)ng/ml、Ⅳ型胶原为(204.1±78.1)ng/m,谷丙转氨酶为(169.87±13.32)U/L、白蛋白为(34.05±6.94)U/L、总胆红素为(48.89±11.03)μmol/L,门静脉直径为(12.9±1.1)mm,脾脏长度为(12.9±1.1)mm、脾脏厚度为(48.6±4.7)mm,观察组透明质酸为(334.7±119.8)ng/ml,层黏连蛋白为(183.2±79.6)ng/ml,Ⅲ型前胶胶原为(252.5±139.8)ng/ml、Ⅳ型胶原为(203.3±74.1)ng/m,谷丙转氨酶为(171.53±11.21)U/L、白蛋白为(33.46±7.53)U/L、总胆红素为(49.33±10.1)μmol/L,门静脉直径为(13.1±0.7)mm,脾脏长度为(122.1±3.9)mm、脾脏厚度为(48.9±4.2)mm,两组无显著性统计学差异;治疗后,对照组透明质酸为(205.2±49.6)ng/ml,层黏连蛋白为(149.8±64.3)ng/ml,Ⅲ型前胶胶原为(192.7±99.8)ng/ml、Ⅳ型胶原为(159.2±42.5)ng/m,谷丙转氨酶为(54.89±6.65)U/L、白蛋白为(35.59±7.2)U/L、总胆红素为(20.89±9.65)μmol/L,门静脉直径为(11.7±0.85)mm,脾脏长度为(117.3±2.9)mm、脾脏厚度为(46.8±3.6)mm,观察组透明质酸为(158.2±79.1)ng/ml,层黏连蛋白为(104.3±59.7)ng/ml,Ⅲ型前胶胶原为(140.2±76.4)ng/ml、Ⅳ型胶原为(111.4±56.8)ng/m,谷丙转氨酶为(24.37±7.33)U/L、白蛋白为(41.02±6.3)U/L、总胆红素为(10.32±8.03)μmol/L,门静脉直径为(10.2±0.5)mm,脾脏长度为(109.4±3.1)mm、脾脏厚度为(44.4±2.0)mm,两组间具有显著性统计学差异(P<0.05);治疗48结束时,观察组患者血清HBV DNA阴转率为83.3%,明显高于对照组治疗后的40%(P<0.05)。结论恩替卡韦联合扶正化瘀胶囊治疗肝硬化患者,其疗效明显优于单用恩替卡韦。

Jak/Stat信号通路在经典CCl_4大鼠肝纤维化模型中的动态变化及扶正化瘀方对其影响

目的探讨Jak/Stat信号通路在经典的CCl4大鼠肝纤维化模型中的动态变化及扶正化瘀方对其影响。方法复制经典的CCl4大鼠肝纤维化模型和肝纤维化扶正化瘀方干预模型,收集纤维化形成、逆转和干预过程中不同时间的血液和肝组织,观察血清指标、肝组织病理、α-SMA表达及肝组织Jak1、Stat3蛋白和mRNA表达变化。多组间比较采用单因素方差分析。结果 CCl4应用后模型组大鼠肝组织炎症及纤维化逐渐加重,α-SMA及Jak1、Stat3表达逐渐升高,8周时达高峰。8周后随着CCl4停用,大鼠肝组织炎症和纤维化逐渐好转,上述指标亦较前明显降低;扶正化瘀方干预组第4、6、8周时大鼠血清指标,肝组织炎症和纤维化程度、Jak1、Stat3表达均较模型组相同时间点明显降低。结论 Jak/Stat信号通路在肝纤维化发生和逆转中发挥重要作用,扶正化瘀方可通过阻断Jak/Stat通路及减少肝星状细胞活化发挥抗肝纤维化作用。

扶正化瘀方及其拆方对肝星状细胞活化的影响

目的:观察扶正化瘀方抗肝纤维化的不同药物配伍的药效作用。方法:分离培养大鼠肝星状细胞,将扶正化瘀方拆方为扶正、化瘀、丹参、虫草、丹参+虫草等组,制备其大鼠药物血清,温育星状细胞。~3H-TdR掺入法测定细胞增殖,ELISA法测定细胞上清Ⅰ型胶原含量,并测定细胞层总蛋白含量以校正胶原含量。RT-PCR法观察前胶原α_2(1)mRNA的表达。结果:全方组及各拆方组对星状细胞的增殖、胶原蛋白分泌及α_2(Ⅰ)前胶原mRNA表达均有不同程度的抑制作用。化瘀组对细胞增殖抑制作用最强,扶正组对胶原生成及基因表达抑制作用最强,而全方组介于两者之间。结论:扶正化瘀方及各拆方对星状细胞的活化功能有不同的作用影响,全方组有整体优势,其抗肝纤维化的主要作用机理可能在于抑制星状细胞的活化。

扶正化瘀胶囊治疗慢性阻塞性肺疾病的临床研究

客观评价扶正化瘀胶囊治疗慢性阻塞性肺疾病的临床疗效,初步探索其作用途径。方法:研究采用随机、平行、对照的临床研究方法。62例患者被随机分入扶正化瘀治疗组(30例)和对照组(32例)。组间资料采用成组独立t检验,组内资料采用配对t检验,计数资料采用卡方检验。结果:扶正化瘀胶囊组"喘"证候治疗前后组内有显著差别(P<0.05),较对照组也有明显差异(P<0.05)。扶正化瘀胶囊中医总有效率为73.33%,经统计未发现与对照组存在差异(P>0.05)。扶正化瘀胶囊组肺功能IC%治疗后较治疗前有明显提升(P<0.05),组间分析FEV1%和IC%存在差异(P<0.05)。结论:扶正化瘀胶囊能够明确改善慢阻肺患者喘的症状,对慢阻肺患者有一定中医疗效,具有改善慢阻肺患者肺功能的作用。

阿德福韦酯联合扶正化瘀胶囊治疗慢性乙型病毒性肝炎肝纤维化临床观察

目的探讨阿德福韦酯联合扶正化瘀胶囊对慢性乙型病毒性肝炎肝纤维化指标的影响。方法 70例慢性乙型病毒性肝炎患者被随机分为联合治疗组(n=35,阿德福韦酯联合扶正化瘀胶囊)和对照组(n=35,单用阿德福韦酯),临床观察48周疗效。结果联合治疗组患者48周后肝纤维化指标下降幅度明显高于对照组(P<0.05);联合治疗组48周时脾脏厚度恢复正常,门静脉内径明显缩小,与治疗前比较,差异均有显著性意义(P<0.05);其中48周时联合治疗组与单药治疗组比较,差异有显著性意义(P<0.05)。结论 阿德福韦酯联合扶正化瘀胶囊治疗肝纤维化疗效优于单药阿德福韦酯治疗。

扶正化瘀方对大鼠CCl_4损伤肝Kupffer细胞功能的影响

目的:探讨扶正化瘀方对大鼠急性CCl_4损伤肝Kupffer细胞功能的影响。方法:体外分离培养大鼠息性CCl_4损伤肝Kupffer细胞,制备扶正化瘀方药物血清对其进行干预,观察药物对其PDGF和TGFβ活性以及对Kupffer细胞线拉体呼吸功能的影响。结果:药物组PDGF和TGFβ活性均显著降低(P<0.05);药物组线粒体呼吸功能明显降低(P<0.05)。结论:扶正化疼方对大鼠急性CCl_4损伤肝Kupffer细胞活化有抑制作用,可能抑制肝星状细胞旁分泌激活,是该方抗肝纤维化的作用机理之一。

扶正化瘀胶囊对心肌梗死大鼠心肌缝隙连接蛋白43表达的影响

目的研究扶正化瘀胶囊对心肌梗死大鼠心肌缝隙连接蛋白43(connexin43,CX43)表达的影响。方法SD雄性大鼠随机分为假手术组、模型组以及扶正化瘀胶囊组和卡托普利组,每组各6只,采用结扎左冠状动脉前降支造成心肌梗死。术后10d开始灌胃给药,持续8周。用免疫组织化学方法观察心肌CX43表达的变化。结果在心肌梗死区域内,模型组与假手术组比较,CX43排列紊乱,阳性表达面积、平均光密度值和积分光密度均显著低于假手术组(P<0.01)。在梗死边缘区,扶正化瘀胶囊组CX43平均光密度值高于模型组(P<0.01),积分光密度高于模型组(P<0.05),CX43排列紊乱有所减轻,阳性表达面积与模型组无统计学意义。卡托普利组CX43平均光密度值高于模型组(P<0.01),积分光密度和阳性表达面积均高于模型组(P<0.05),CX43排列紊乱也有减轻。结论扶正化瘀胶囊能够部分改善心肌梗死大鼠心肌的CX43重构。

阿德福韦酯联合扶正化瘀胶囊治疗慢性乙型肝炎有效性与安全性的Meta分析

目的系统评价阿德福韦酯联合扶正化瘀胶囊(ADF+FC)及单用阿德福韦酯(ADF)治疗慢性乙型肝炎的有效性与安全性。方法计算机检索CNKI、万方数据库、PubMed、CBM、Medline、Web of Knowledge以及Elsevier数据库,检索时间均为从建库至2012年11月。2名研究者独立选择试验、质量评价及提取资料,采用RevMan4.3.2软件进行Meta分析。结果最终纳入5个随机对照试验(RCT),共455例患者。Meta分析结果显示:Ⅲ型原胶原比较,联合组优于单用组(SMD=-0.98,95%CI(-1.26,-0.71));层黏蛋白比较,联合组优于单用组(SMD=-0.69,95%CI(-0.88,-0.50));Ⅳ型胶原比较,联合组优于单用组(SMD=-0.50,95%CI(-0.93,-0.07));天门冬氨酸氨基转移酶比较,联合组优于单用组(SMD=-0.69,95%CI(-0.97,-0.41));门静脉直径比较,联合组优于单用组(SMD=-0.50,95%CI(-0.74,-0.26))。结论阿德福韦酯联合扶正化瘀胶囊治疗慢性乙型肝炎效果优于单用阿德福韦酯,但受纳入文献的数量和质量限制,以上结论需高质量大范围的临床试验进一步认证。

扶正化瘀胶囊联合核苷类抗病毒药物治疗慢性乙型肝炎的meta分析

目的系统评价扶正化瘀胶囊联合核苷类抗病毒药物治疗慢性乙型肝炎的疗效。方法纳入文献中以核苷类抗病毒药物为对照组,以扶正化瘀胶囊联合核苷类抗病毒药物为试验组。由2名研究者独立评价纳入研究的方法学质量,并采用RevMan 5.1软件进行meta分析。结果共纳入17个随机对照试验,合计1 320例慢性乙型肝炎患者,其中对照组636例,试验组684例,1个研究方法学质量为B级,16个研究方法学质量为C级。meta分析结果显示:肝功能4个指标(丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素、白蛋白)在治疗24周时2组无统计学差异(P>0.05),进一步治疗到48周时试验组前3个指标明显下降,最后1个指标明显上升(P<0.05)。肝纤维化指标(透明质酸、Ⅳ型胶原)在治疗24周时2组有统计差异(P<0.05),48周时2个指标值进一步降低(P<0.05)。解剖学指标(门静脉直径)在治疗24周时2组无统计学差别(P>0.05),试验组脾脏厚度有明显减小(P<0.05),进一步观察48周后发现门静脉直径开始减小(P<0.05),而脾脏厚度进一步减小(P<0.05)。血清病毒学指标(HBeAg阴转率、HBV-DNA阴转率)在治疗24、48周时均无明显改善(P>0.05)。结论本系统评价结果表明,扶正化瘀胶囊联合核苷类抗病毒药在治疗48周时能明显改善慢性乙型肝炎患者肝功能、肝纤维化、解剖学指标,但对血清病毒学指标无明显改善作用。

扶正化瘀方对非酒精性脂肪性肝纤维化及uPA/PAI-1的作用及机制

目的探明非酒精性脂肪性肝纤维化进展中扶正化瘀方对小鼠肝组织uPA/PAI-1表达的影响及作用机制。方法选用7～8周龄健康雄性C57BL/6J小鼠,蛋氨酸-胆碱缺乏(methionine and choline deficient,MCD)饮食喂养8周,建立非酒精性脂肪性肝纤维化模型,采用扶正化瘀方进行干预实验,蛋氨酸-胆碱充足饮食设立对照组。HE、Masson染色观察肝脂肪变、炎性反应及纤维化程度;RT-PCR和Western印迹检测肝组织纤溶酶原激活物抑制因子-1(plasminogen activator inhibitor-1,PAI-1)、尿激酶型纤溶酶原激活物(urokinase type plasminogen activator,uPA)、转化生长因子β1(transforming growth factor beta1,TGF-β1)mRNA及蛋白的表达。多组间比较采用单因素方差分析,组间比较采用Student-Newman-Keuls法。结果模型组小鼠肝组织呈现大泡性肝细胞脂肪变,伴肝细胞气球样变、小叶内点/灶状坏死及炎性细胞浸润、可见窦周纤维化及纤维间隔形成,肝组织PAI-1、uPA、TGF-β1mRNA及蛋白表达水平较对照组显著升高;应用扶正化瘀方组小鼠肝脂肪变、炎性反应及纤维化程度较模型组明显减轻,PAI-1、TGF-β1mRNA及蛋白表达显著减少(P<0.05),而uPA表达显著增多(P<0.05)。对照组、模型组、扶正化瘀方组上述基因mRNA及蛋白表达水平依次为,PAI-1:0.25±0.02、1.43±0.10、0.84±0.16和0.30±0.08、1.40±0.16、0.90±0.17;uPA:0.42±0.02、1.03±0.13、1.22±0.06和0.34±0.08、1.15±0.07、1.44±0.07;TGF-β1:0.54±0.06、1.17±0.06、1.02±0.07和0.37±0.07、1.43±0.13、0.99±0.13(P<0.05)。结论扶正化瘀方可通过上调uPA、下调PAI-1及TGF-β1表达,阻止小鼠非酒精性脂肪性肝纤维化的发生与发展。

扶正化瘀胶囊联合阿德福韦酯治疗慢性乙型肝炎肝纤维化的疗效观察

目的观察扶正化瘀胶囊联合阿德福韦酯在慢性乙型肝炎患者抗肝纤维化的疗效。方法选取50例慢性乙型肝炎患者,随机分为治疗组(扶正化瘀胶囊联合阿德福韦酯)及对照组(单用阿德福韦酯)。观察治疗前、治疗后48周时,两组患者症状、体征、肝功能、HBV DNA、HBeAg及肝纤维化指标变化,按非创伤性指标的肝纤维化疗效评估标准评价疗效。结果治疗48周后,两组患者的症状及体征均较治疗前明显改善,ALT复常率、HBV DNA转阴率、HBeAg血清转换率两组比较均无显著性差异(P>0.05)。但治疗组患者肝纤维化指标下降程度、门静脉内径及脾脏厚度的改善均明显优于对照组(P<0.05)。两组患者在治疗过程中未见明显不良反应。结论扶正化瘀胶囊联合阿德福韦酯治疗慢性乙型肝炎改善肝纤维化具有更好的作用。

扶正化瘀胶囊联合熊去氧胆酸胶囊治疗原发性胆汁性肝硬化临床研究

目的观察扶正化瘀胶囊联合熊去氧胆酸胶囊对原发性胆汁性肝硬化(PBC)患者症状、血清细胞因子、免疫相关指标的影响。方法选择PBC患者60例,随机分为实验组及对照组各30例。实验组给予扶正化瘀胶囊联合熊去氧胆酸胶囊口服,对照组单用熊去氧胆酸胶囊口服,疗程均为24周。记录并分析治疗12、24周患者中医临床症状、抗线粒体抗体(AMA)、抗线粒体抗体-M2亚型(AMA-M2)、免疫球蛋白G(IgG)、免疫球蛋白M(IgM)、免疫球蛋白A(IgA)、免疫球蛋白B(IgB)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(GGT)、ALT、AST、TBil及总胆固醇(CH)、甘油三酯(TG)等各项指标的变化。结果两组患者在治疗12、24周ALT、AST、TBil、ALP、GGT、TG、CH、AMA、AMA-M2、IgM与治疗前组内比较均改善显著,差异均有统计学意义(P均<0.05);而IgA、IgB、IgG与治疗前组内比较均无明显改善,差异均无统计学意义(P均>0.05)。实验组治疗12、24周中医临床症状较前明显改善,而对照组治疗12周中医临床症状无改善,治疗24周中医临床症状略有改善,但治疗前后差异无统计学意义(P>0.05)。实验组治疗12、24周中医临床症状、ALP、GGT、ALT、AST、TG、AMA-M2均较对照组明显改善,差异均有统计学意义(P均<0.05),而实验组治疗12周AMA、IgM及TBil与治疗前比较略有下降,但与对照组比较差异无统计学意义(P均>0.05)。实验组治疗24周中医临床症状、ALP、GGT、ALT、AST、TG、AMA-M2较对照组均有显著下降,差异有统计学意义(P<0.05)。结论熊去氧胆酸胶囊联合扶正化瘀胶囊治疗PBC,在改善中医临床症状、转氨酶及线粒体抗体方面较单纯使用熊去氧胆酸胶囊有明显疗效,但对降低CH、lgA、IgB、IgG无显著作用。

四氯化碳蒸熏法致肝细胞急性损伤时的功能变化及扶正化瘀方药物血清的调节作用

目的:研究体外急性损伤肝细胞的功能变化和扶正化瘀方药物血清的调节作用。方法:采用四氯化碳蒸熏法造成体外原代培养大鼠肝细胞急性肝损伤,检测其释放ALT、AST活性,分泌白蛋白及细胞内外胶原生成率的变化,同时通过添加体内给药后分离的药物血清,观察扶正化瘀方对急性损伤肝细胞病理变化的影响。结果:CCl_4体外急性损伤肝细胞后,其培养液中ALT、AST活性及胶原生成率显著升高,增殖能力明显降低,Alb变化不明显,扶正化瘀方药物血清能显著促进损伤肝细胞的增殖,有效地抑制损伤肝细胞培养上清波中ALT、AST活性,抑制损伤肝细胞的胶原生成率。结论:在急性损伤肝细胞状态,胶原合成已被启动,扶正化瘀方适当剂量具有保护肝细胞、抑制胶原生成的作用。

含药血清药理法观察扶正化瘀方抗肝纤维化的配伍作用

将扶正化瘀方分为扶正组、化瘀组、虫草组、丹参组及丹参加虫草组,灌胃给药分离药物血清,观察各药物血清对大鼠肝星状细胞增殖、活化、型胶原和TGFβ1蛋白及其mRNA表达的影响。各组药物血清均可抑制星状细胞的增殖和活化,其中化瘀组效果最明显;各组药物血清均可抑制星状细胞型胶原mRNA及其蛋白的生成,以扶正组效果最佳;各组药物血清星状细胞TGFβ1mRNA及其蛋白生成均有明显的降低,以虫草组作用最强。

扶正化瘀胶囊对抗病毒有效的乙型肝炎肝硬化患者外周血细胞因子的调节

目的观察扶正化瘀胶囊对抗病毒有效的乙型肝炎肝硬化患者外周血细胞因子的分泌、肝功能及肝硬化程度的影响。方法收集恩替卡韦抗病毒治疗有效的乙型肝炎肝硬化患者63例,将其分为扶正化瘀组(FZHY组)30例,均用恩替卡韦联合扶正化瘀胶囊治疗;对照组33例,均单用恩替卡韦治疗;另选20名健康体检者作为健康对照组。治疗1年后分别观察乙型肝炎肝硬化患者肝硬化程度(肝硬度扫描,FibroScan),肝功能(ALT、AST、Alb、TBil)。比较3组外周血细胞因子(IL-1α、IL-1β、IL-4、IL-6、IL-8、IL-10、IL-13、MCP-1、INF-γ、TNF-α、TGF-β1)表达。结果较治疗前FZHY组患者ALT(36.00±19.74 vs 22.82±9.32)IU/L、AST(48.08±26.38 vs 34.47±17.14)IU/L显著下降(P<0.05,P<0.01)。FZHY组肝硬度有所下降(22.53±20.80 vs 14.28±10.40)kPa(P<0.05)。治疗后,FZHY组患者TGF-β1(1107.12±414.36 vs 512.24±219.36)pg/mL,IL-13(33.23±17.95 vs 13.58±17.93)pg/mL显著下降(P<0.01)。结论扶正化瘀胶囊可以减少炎性因子的分泌,从而抑制抗病毒有效的乙型肝炎肝硬化患者的进展。