目的:观察腺苷蛋氨酸联合肝爽颗粒治疗酒精性肝病患者的临床疗效及对肝纤维化指标的影响.方法:选取2019年7月至2021年6月陕西中医药大学附属医院肝病医院收治的110例酒精性肝病患者作为研究对象,按照随机数字表法随机分为观察组和对照组,每组55例.对照组给予酒精性肝病基础疗法结合肝爽颗粒治疗,肝爽颗粒温开水冲服,1袋/次,3次/d.观察组给予丁二磺酸腺苷蛋氨酸联合肝爽颗粒治疗,肝爽颗粒服用方案同对照组,同时注射丁二磺酸腺苷蛋氨酸1.0 g+250 mL0.9％氯化钠注射液缓慢静脉滴注,1次/d.2组均1个月为1个疗程,治疗3个疗程.分别于治疗前后检测肝功指标[直接胆红素(DBIL)、谷氨酰转移酶(GGT)、胆汁酸(BA)]、肝纤维化指标[脯氨酸肽酶(PLD)、Ⅳ型胶原(Ⅳ-C)、Ⅰ型前胶原氨端肽原(PINP)]、炎症介质[干扰素诱导蛋白-10(IP-10)、C-X-C基序趋化因子配体1(CXCL1)、可溶性血管细胞黏附分子-1(VCAM-1)],记录2组患者治疗期间发生的不良反应,计算总有效率.结果:治疗后,2组患者DBIL、GGT、BA水平均较治疗前降低,且观察组DBIL、GGT、BA水平均低于对照组,差异有统计学意义(P＜0.05);治疗后,2组患者PLD、Ⅳ-C、PINP水平均较治疗前降低,且观察组PLD、Ⅳ-C、PINP水平均低于对照组,差异有统计学意义(P＜0.05).治疗后,2组患者IP-10、CXCL1、VCAM-1水平均较治疗前降低,且观察组I P-10、CXCL1、VCAM-1水平均低于对照组,差异有统计学意义(P＜0.05).治疗期间观察组、对照组患者不良反应发生率分别为12.73％(7/55)、9.09％(5/55),差异无统计学意义(P＞0.05).观察组、对照组总有效率分别为90.91％(50/55)、74.55％(41/55),观察组总有效率高于对照组,差异有统计学意义(P＞0.05)o结论:丁二磺酸腺苷蛋氨酸联合肝爽颗粒治疗酒精性肝病效果显著,可改善肝功能及肝纤维化状态,降低炎症介质水平,治疗安全性较高.

目的 探讨贝达喹啉联合肝爽颗粒治疗耐多药肺结核(multidrug resistant tuberculosis,MDR-TB)的应用效果及对γ 干扰素诱导蛋白10(interferon-γ inducible protein-10,IP-10)、细胞因子信号传导抑制蛋白1(suppressors of cytokine signaling,SOCS1)的影响.方法 按1:1倾向性匹配原则将2022年1月至2022年10月河北省胸科医院结核四科收治的144例MDR-TB患者分为对照1组、对照2组及联合组,各48例.3组均在予以常规治疗基础上,对照1组予以肝爽颗粒,对照2组予以贝达喹啉,联合组予以肝爽颗粒和贝达喹啉.比较3组治疗第4、8、12、24、36、48周痰菌转阴率及中位转阴时间.比较3组治疗48周后病灶吸收情况、空洞变化情况.比较3组治疗前、治疗第8、24、48周血清炎症因子[干扰素-γ(interferon-γ,IFN-γ)、白细胞介素(interleukin,Il)-4、Il-17、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、IP-10、SOCS1]水平及受试期间不良反应发生情况.结果 对照2组、联合组第4、8、12、24、36、48周痰菌转阴率均高于对照1组(P均<0.05);对照2组、联合组中位转阴时间均早于对照1组(P均<0.05);对照2组、联合组病灶吸收率分别为93.75％、95.83％,均高于对照1组56.25％(P均<0.05);对照2组、联合组空洞改善率分别为95.83％、95.83％,均高于对照1组62.50％(P均<0.05);联合组第8、24、48周IL-17、TNF-α、IL-4水平<对照2组<对照1组(P均<0.05);联合组第8、24、48周IP-10、SOCS1水平<对照2组<对照1组(P均<0.05);对照2组、联合组心电图异常率分别为16.67％、12.50％,均高于对照1组(0)％(P均<0.05);联合组肝损伤和胃肠系统不良反应发生率均为0,分别低于对照2组12.50％、16.67％ 和对照1组14.58％、14.58％(P均<0.05).结论 含贝达喹啉治疗方案能提高MDR-TB的病灶吸收率、空洞闭合率、痰菌转阴率,抑制炎症反应,联合肝爽颗粒虽未增强疗效,但能进一步改善炎症反应,减少肝损伤和胃肠道不良反应的发生,可能有助于增加患者贝达喹啉治疗的耐受性和依从性.

目的 探讨肝爽颗粒治疗原发性胆汁性胆管炎(primary biliary cholangitis,PBC)的疗效及对患者肝功能及肝纤维化的影响.方法 采用随机数字表法将于2019年12月-2022年3月在衡水市第三人民医院接受治疗的68例PBC患者分为A组和B组,各34例.A组给予熊去氧胆酸片,B组在A组基础上给予肝爽颗粒.两组均持续治疗3个月e比较两组治疗3个月后的疗效,治疗前、治疗3个月后的肝功能、肝纤维化指标、血清白细胞介素-6(interleukin-6,IL-6)、核因子相关因子2(Nrf2)、血红素加氧酶-1(hemoglobin oxygenase-1,HO-1),治疗期间的安全性.结果 B组治疗3个月后的总有效率为97.06％(33/34),高于A组的76.47％(26/34)(P＜0.05).两组治疗3个月后的血清天冬氨酸转氨酶(aspartate aminotransferase,AST)、丙氨酸转氨酶(alanine aminotransferase,ALT)、γ-谷氨酰转肤酶(γ-glutamyl transpeptidase,GGT)、透明质酸(hyaluronic acid,HA)、层黏连蛋白(laminin,LN)、Ⅲ型前胶原肽(type Ⅲ procollagen pep-tide,PC Ⅲ)及IL-6水平均比治疗前低,且与A组进行比较,B组较低;两组治疗3个月后的血清Nrf2、HO-1水平均比治疗前高,且与A组进行比较,B组高于A组(P＜0.05).B组及A组治疗期间的不良反应发生率比较,差异无统计学意义[17.65％(6/34)vs 11.76％(4/34),P＞0.05].结论 肝爽颗粒可有效减轻PBC患者炎症反应及氧化应激反应,并抑制患者肝纤维化,进一步提高患者肝功能,具有较高临床疗效,且其安全性良好.

目的 通过多技术联用的方法筛选肝爽颗粒抗肝纤维化的药效成分.方法 采用UPLC-Q-TOF-MS/MS技术和UNIFI软件,根据质谱相对分子质量、裂解规律、文献报道等方法对肝爽颗粒70％醇提取物和大鼠灌胃后血清中化学物质质谱碎片信息进行分析,以明确其药效物质基础.使用转化生长因子β1(TGF-β1)(10ng·mL-1)诱导肝星状细胞(HSC-T6)构建肝纤维化细胞模型,采用细胞增殖检测(CCK-8)法检测各组细胞增殖情况.结果 在肝爽颗粒提取液中共鉴定出84个化学成分,在大鼠给药后的血清中共鉴定出21个原形成分,其中党参碱、柴胡皂苷A、柴胡皂苷D、木犀草素、山柰酚、黄芩苷等均可抑制肝星状细胞生长,为肝爽颗粒抗肝纤维化的药效成分.结论 本研究阐明了肝爽颗粒抗肝纤维化的药效物质基础,可为肝爽颗粒保肝作用机制及产品质量控制研究提供参考.

OBJECTIVE:To investigate the potential pharmacological mechanisms of Ganshuang granules(肝爽颗粒,GSG)in treating non-alcoholic fatty liver(NAFLD).METHODS:All the active components and targets of GSG were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.Protein-Protein interaction network,Kyoto Encyclopedia of Genes and Genomes and Gene Ontology function annotation of common targets were analyzed to predict the mechanisms of action of GSG in the treatment of NAFLD.Then,the mouse models of NAFLD were constructed in a diet-induced manner and treated with GSG.The levels of interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-a)and phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)pathway-related proteins in the liver of mice in each group were measured by enzyme linked immunosorbent assay and Western blot,respectively.RESULTS:Network pharmacology revealed a total of 159 potential targets of GSG for the treatment of NAFLD.Functional enrichment analysis indicated that the PI3K/AKT signaling pathway may be involved during GSG treatment of NAFLD.Further experiments showed that the significantly decreased alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,total cholesterol,triglyceride and low-density lipoprotein cholesterol levels in NAFLD model mice serum after GSG treatment,as well as the expression levels of IL-6 and TNF-α in the liver.Furthermore,drug intervention increased the protein expression levels of phosphorylated-PI3K(P-PI3K)and P-AKT in the liver of the model group mice,and decreased the protein expression level of sterol regulatory element-binding protein 1.CONCLUSION:We found that GSG is effective in treating NAFLD and the potential therapeutic targets may be involved in PI3K/AKT signaling pathway.

目的 考察肝爽颗粒对抗初治肺结核引起药物性肝损伤的影响.方法 回顾性收集180例患者,对照组(83例)给予2HRZE/4HR,观察组(97例)在对照组基础上加用肝爽颗粒.采用Kaplan-Meier法比较2组药物性肝损伤累积发生率,COX比例风险分析考察其发生风险及影响因素,并检测不良反应发生率.结果 观察组药物性肝损伤累积发生率低于对照组(P=0.001),相对危险度为3.873(95％CI:1.732,8.661).调整年龄、性别、白蛋白、肝肾功能等项目后,HBsAg阳性、肺外结核、肝爽颗粒治疗是独立影响因素(P＜0.05).2组不良反应发生率比较,差异无统计学意义(P＞0.05).结论 肝爽颗粒可安全有效地降低初治肺结核患者药物性肝损伤发生率,保障疗程完成,提高治愈率.

目的:评价肝爽颗粒治疗慢性乙型肝炎患者的临床疗效及安全性.方法:选择慢性乙型病毒性肝炎患者65例,随机分为治疗组33例和对照组32例.治疗组服用肝爽颗粒,每次l袋,每天3次,及水飞蓟宾葡甲胺片,每次2粒,每天3次;对照组服用水飞蓟宾葡甲胺片,每次2粒,每天3次,疗程均为6个月.记录入组病例的一般情况、临床症状,检测治疗前、治疗3个月、治疗6个月的肝功能、凝血指标、肝纤维化指标、免疫指标、Fibroscan值、治疗前后完善肝穿活检评估肝脏炎性活动度分级及纤维化程度分期.结果:与治疗前比较,治疗后治疗组总胆红素下降、凝血酶原时间缩短(P＜0.05),对照组未见显著差异.肝穿活检炎性活动度分级及纤维化程度分期有效率比较,治疗组优于对照组(P＜0.05).两组均无严重不良事件发生.结论:肝爽颗粒治疗慢性乙型肝炎可改善肝脏炎性活动度及纤维化程度,药物具有良好安全性.

Objective:To investigate the potential antifibrotic mechanisms of Chinese medicine Ganshuang Granules(肝爽颗粒, GSG) and to provide clinical therapeutic evidence of its effects.Methods:A cirrhotic mouse model was established by intraperitoneally injecting a mixture of CCl4 (40％) and oil (60％) at 0.2 mL per 100 g of body weight twice a week for 12 weeks.After 12-week modeling,GSG was intragastric administrated to the mice for 2 weeks,and the mice were divided into low-,medium-and high-dose groups at doses of 1,2 and 4 g/(kg·day),respectively.Liver morphology changes were observed using Masson's trichrome staining and B-ultrasound.The levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST) and hyaluronic acid (HA) in serum were detected using an automatic biochemistry analyzer.The expressions of desmin,smooth muscle actin (SMA) and Foxp3 in liver were detected by immunofluorescence.The regulatory T cell (Treg) frequency was determined through flow cytometry analysis.Collagen-Ⅰ,SMA,IL-6,tumor necrosis factor α (TNF-α),interleukin (IL)-1 β and transforming growth factor β 1 (TGF-β 1) expression levels were measured using quantitative polymerase chain reaction (qPCR).Results:Masson's staining result showed fewer pseudolobule structures and fibrous connective tissue in the GSG-treatment groups than in the spontaneous recovery group.Ultrasonography showed that GSG treatment reduced the number of punctate hyperechoic lesions in mice cirrhotic livers.The serum ALT,AST,HA levels were significantly ameliorated by GSG treatment (ALT:F=8.104,P=0.000;AST:F=7.078,P=0.002;and HA:F=7.621,P=0.001).The expression levels of collagen-Ⅰ and SMA in the cirrhotic livers were also attenuated by GSG treatment (collagen-Ⅰ:F=3.938,P=0.011;SMA:F=4.115,P=0.009).Tregs,which were elevated in the fibrotic livers,were suppressed by GSG treatment (F=8.268,P=0.001).The expressions of IL-6,TNF-α and IL-1 β increased,and TGF-β levels decreased in the cirrhotic livers after GSG treatment (IL-6:F=5.457,P=0.004;TNF-α:F=6.023,P=0.002;IL-1 β:F=6.658,P=0.001;and TGF-β 1:F=1 1.239,P=0.000).Conclusions:GSG promoted the resolution/regression of cirrhosis and restored liver functions in part by suppressing Treg cell differentiation,which may be mediated by hepatic stellate cells.

肝纤维化是贯穿慢性乙型肝炎(CHB)和肝炎肝硬化各临床阶段的基本病理过程,如果不予有效治疗,可进展为肝硬化,并产生肝细胞功能障碍及门脉高压等一系列并发症,是肝细胞癌发生的重要病理基础[1].CHB目前尚无特效治疗,干扰素及核苷类药物为仅有的两种抗HBV药物,但常因患者依从性及免疫状态等因素不能达到理想的疗效,而使病情反复,大多数患者存在不同程度的肝纤维化[2].中医药在抗肝纤维化治疗中有明显的优势,而且其作用机制是多靶点[3].笔者采用恩替卡韦联合肝爽颗粒治疗62例乙型肝炎肝纤维化患者,取得良好效果,现报告如下.

目的 探讨肝爽颗粒主要成分柚皮苷是否具有预防药物性肝损伤的功能以及保护作用的机制.方法 选取具有肝毒性的药物(曲格列酮和双氯芬酸钠)制造体外模型,预防性地应用不同浓度的柚皮苷,通过半数抑制率(IC50)、转氨酶水平、乳酸脱氢酶水平、Caspase3基因水平评价HL-7702细胞的损伤情况.评价不同浓度的柚皮苷对细胞色素P450(CYP450)家族基因的改变情况.结果 柚皮苷能够明显升高曲格列酮和双氯芬酸钠的IC50,具有降低转氨酶、Caspase3表达的作用.但这种改善具有剂量依赖性,其中100μmol/L柚皮苷的保护作用最明显,1μmol/L柚皮苷和10μmol/L柚皮苷的保护作用不明显.比较CYP代谢酶基因改变情况发现,100μmol/L柚皮苷能明显抑制其表达(P<0.05),1μmol/L柚皮苷和10μmol/L柚皮苷的抑制作用不明显.结论 肝爽颗粒主要成分柚皮苷能够通过抑制CYP450酶的功能,从而起到预防作用.