Effects of Yinchenhao Decoction on Self-regulation of Renin-angiotensin System by Targeting Angiotensin Converting Enzyme 2 in Bile Duct-ligated Rat Liver

Summary： In order to investigate whether Yinchenhao decoction （YCHD） attenuates hepatic fibro- genesis in the bile duct ligation （BDL） model via recovering and restoring the self-regulation and bal- ance of the renin-angiotensin system （RAS）, 33 specific-pathogen-free （SPF） male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows： G1, the sham group （n=4）; G2, BDL 7-day group （n=5）; G3, BDL＋YCHD 430 mg/mL （n=8）; G4, BDL＋losartan 0.65 mg/mL （ARB group, n=8）; G5, model group （BDL without any treatment, n=8）. YCHD and losartan （10 mL.kgl.day-1） were given by gastric gavage for 16 days following BDL in G3 and G4 groups, respec- tively. The effect of YCHD on liver fibrosis and the detailed molecular mechanisms were assessed by liver function including total bilirubin （TBIL）, direct bilirubin （DBIL）, indirect bilirubin （IDBIL）, alanine aminotransferase （ALT）, and aspartate aminotransferase （AST）. Histological changes were ob-. served by transmission electron microscopy （TEM） and Masson trichrome staining. Western blotting was used to detect the protein expression level of the renin-angiotensin system （RAS） components in- cluding angiotensin converting enzyme （ACE）, angiotensin II type 1 receptor （AT1R）, ACE2, angio- tensin II （Ang II） as well as transforming growth factor 131 （TGF131）. The experimental data were ana- lyzed by principle component analytical method of pattern recognition. The results showed that bio- chemically, serum TBIL, DBIL, IDBIL, ALT and AST levels were markedly increased following BDL as compared with the sham group （P〈0.05）. Serum TBIL, IDBIL and DBIL levels in G3 group were dramatically decreased as compared with G5 and G4 groups （P〈0.05）. Serum AST level in G3 was sig- nificantly lowered than in G5 group （P〈0.05）, but there was no significant difference in ALT among G3, G4 and G5 groups （P〉0.05）. Histologically, livers in G3 group showed less hepatocytes necrosis, less bile duct hyperplasia and less collagen formation than in G4 and G5 groups. The protein expression lev- els of ACE2, ACE, Ang II, AT1R and TGF131 in G2, G3 and G4 groups were significantly higher than in sham group （P〈0.05）, and lower than in G5 group （P〈0.05）. However, the differences among G2, G3 and G4 groups were not significant （P〉0.05）. ACE2 protein expression in G3 group was significantly higher than in G2 group （P〈0.05） and there was no significant difference in comparison with G4 group （P〉0.05）. Moreover, the protein expression of TGF131 in G3 group was significantly lower than in G5 and G4 groups （P〈0.05）. Our findings suggest that the antifibrotic effects of YCHD may be associated with the decreased classical RAS pathway components and TGFI31 downexpression so as to recover and rebuild self-regulation of the RAS by elevating the protein expression of ACE2.

Yinchenhao decoction attenuates obstructive jaundice-induced liver injury and hepatocyte apoptosis by suppressing protein kinase RNA-like endoplasmic reticulum kinase-induced pathway

BACKGROUND Chronic biliary obstruction results in ischemia and hypoxia of hepatocytes,and leads to apoptosis.Apoptosis is very important in regulating the homeostasis of the hepatobiliary system.Endoplasmic reticulum(ER)stress is one of the signaling pathways that induce apoptosis.Moreover,the protein kinase RNA-like endoplasmic reticulum kinase(PERK)-induced apoptotic pathway is the main way;but its role in liver injury remains unclear.Yinchenhao decoction(YCHD)is a traditional Chinese medicine formula that alleviates liver injury and apoptosis,yet its mechanism is unknown.We undertook this study to investigate the effects of YCHD on the expression of ER stress proteins and hepatocyte apoptosis in rats with obstructive jaundice(OJ).AIM To investigate whether YCHD can attenuate OJ-induced liver injury and hepatocyte apoptosis by inhibiting the PERK-CCAAT/enhancer-binding protein homologous protein(CHOP)-growth arrest and DNA damage-inducible protein 34(GADD34)pathway and B cell lymphoma/leukemia-2 related X protein(Bax)/B cell lymphoma/leukemia-2(Bcl-2)ratio.METHODS For in vivo experiments,30 rats were divided into three groups:control group,OJ model group,and YCHD-treated group.Blood was collected to detect the indicators of liver function,and liver tissues were used for histological analysis.For in vitro experiments,30 rats were divided into three groups:G1,G2,and G3.The rats in group G1 had their bile duct exposed without ligation,the rats in group G2 underwent total bile duct ligation,and the rats in group G3 were given a gavage of YCHD.According to the serum pharmacology,serum was extracted and centrifuged from the rat blood to cultivate the BRL-3A cells.Terminal deoxynucleotidyl transferase mediated dUTP nick end-labelling(TUNEL)assay was used to detect BRL-3A hepatocyte apoptosis.Alanine aminotransferase(ALT)and aspartate transaminase(AST)levels in the medium were detected.Western blot and quantitative real-time polymerase chain reaction(qRT-PCR)analyses were used to detect protein and gene expression levels of PERK,CHOP,GADD34,Bax,and Bcl-2 in the liver tissues and BRL-3A cells.RESULTS Biochemical assays and haematoxylin and eosin staining suggested severe liver function injury and liver tissue structure damage in the OJ model group.The TUNEL assay showed that massive BRL-3A rat hepatocyte apoptosis was induced by OJ.Elevated ALT and AST levels in the medium also demonstrated that hepatocytes could be destroyed by OJ.Western blot or qRT-PCR analyses showed that the protein and mRNA expression levels of PERK,CHOP,and GADD34 were significantly increased both in the rat liver tissue and BRL-3A rat hepatocytes by OJ.The Bax and Bcl-2 levels were increased,and the Bax/Bcl-2 ratio was also increased.When YCHD was used,the PERK,CHOP,GADD34,and Bax levels quickly decreased,while the Bcl-2 levels increased,and the Bax/Bcl-2 ratio decreased.CONCLUSION OJ-induced liver injury and hepatocyte apoptosis are associated with the activation of the PERK-CHOP-GADD34 pathway and increased Bax/Bcl-2 ratio.YCHD can attenuate these changes.

The mechanism of Yinchenhao decoction in treating obstructivejaundice- induced liver injury based on Nrf2 signaling pathway

BACKGROUND Obstructive jaundice(OJ)is caused by bile excretion disorder after partial or complete bile duct obstruction.It may cause liver injury through various mechanisms.Traditional Chinese medicine(TCM)has a lot of advantages in treating OJ.The recovery of liver function can be accelerated by combining Chinese medicine treatment with existing clinical practice.Yinchenhao decoction(YCHD),a TCM formula,has been used to treat jaundice.Although much progress has been made in recent years in understanding the mechanism of YCHD in treating OJ-induced liver injury,it is still not clear.AIM To investigate chemical components of YCHD that are effective in the treatment of OJ and predict the mechanism of YCHD.METHODS The active components and putative targets of YCHD were predicted using a network pharmacology approach.Gene Ontology biological process and Kyoto Encyclopedia of Genes and Genomes path enrichment analysis were carried out by cluster profile.We predicted the biological processes,possible targets,and associated signaling pathways that YCHD may involve in the treatment of OJ.Thirty male Sprague–Dawley rats were randomly divided into three groups,each consisting of 10 rats:the sham group(Group S),the OJ model group(Group M),and the YCHDtreated group(Group Y).The sham group only received laparotomy.The OJ model was established by ligating the common bile duct twice in Groups M and Y.For 1 wk,rats in Group Y were given a gavage of YCHD(3.6 mL/kg)twice daily,whereas rats in Groups S and M were given the same amount of physiological saline after intragastric administration daily.After 7 d,all rats were killed,and the liver and blood samples were collected for histopathological and biochemical examinations.Total bilirubin(TBIL),direct bilirubin(DBIL),alanine aminotransferase(ALT),and aspartate transaminase(AST)levels in the blood samples were detected.The gene expression levels of inducible nitric oxide synthase(iNOS)and endothelial nitric oxide synthase(eNOS),and the nucleus positive rate of NF-E2 related factor 2(Nrf2)protein were measured.Western blot analyses were used to detect the protein and gene expression levels of Nrf2,Kelchlike ECH-associated protein 1,NAD(P)H quinone dehydrogenase 1(NQO1),and glutathione-Stransferase(GST)in the liver tissues.One-way analysis of variance was used to evaluate the statistical differences using the statistical package for the social sciences 23.0 software.Intergroup comparisons were followed by the least significant difference test and Dunnett’s test.RESULTS The effects of YCHD on OJ involve biological processes such as DNA transcription factor binding,RNA polymerase II specific regulation,DNA binding transcriptional activator activity,and nuclear receptor activity.The protective effects of YCHD against OJ were closely related to 20 pathways,including the hepatitis-B,the mitogen-activated protein kinase,the phosphatidylinositol 3-kinase/protein kinase B,and tumor necrosis factor signaling pathways.YCHD alleviated the swelling and necrosis of hepatocytes.Following YCHD treatment,the serum levels of TBIL(176.39±17.03μmol/L vs 132.23±13.88μmol/L,P<0.01),DBIL(141.41±14.66μmol/L vs 106.43±10.88μmol/L,P<0.01),ALT(332.07±34.34 U/L vs 269.97±24.78 U/L,P<0.05),and AST(411.44±47.64 U/L vs 305.47±29.36 U/L,P<0.01)decreased.YCHD promoted the translocation of Nrf2 into the nucleus(12.78±0.99%vs 60.77±1.90%,P<0.001).After YCHD treatment,we found a decrease in iNOS(0.30±0.02 vs 0.20±0.02,P<0.001)and an increase in eNOS(0.18±0.02 vs 0.32±0.02,P<0.001).Meanwhile,in OJ rats,YCHD increased the expressions of Nrf2(0.57±0.03 vs 1.18±0.10,P<0.001),NQO1(0.13±0.09 vs 1.19±0.07,P<0.001),and GST(0.12±0.02 vs 0.50±0.05,P<0.001),implying that the potential mechanism of YCHD against OJ-induced liver injury was the upregulation of the Nrf2 signaling pathway.CONCLUSION OJ-induced liver injury is associated with the Nrf2 signaling pathway.YCHD can reduce liver injury and oxidative damage by upregulating the Nrf2 pathway.

A network pharmacological study on the potential mechanism of Yinchenhao Decoction in treatment of chronic hepatitis B

Background: Yinchenhao Decoction (YCHD), an ancient Chinese herbal medicinal compound prescribe for the treatment of jaundice, which long-term clinical experience and randomized trials have shown is effective against chronic hepatitis B (CHB). However, its mechanism remains unknown. With the gradual separation of pharmacodynamic components in YCHD and the development of computer virtual technology, network pharmacology provides an opportunity. Our study is to explore the underlying mechanism of YCHD for the treatment of CHB. Methods: The active compounds of YCHD were screened from TCMSP database, whose targets were predicted based on the ligands structures and the targets of CHB was selected from the TTD, DisGeNET, and Drugbank databases to obtain the potential targets of YCHD for CHB treating. Cytoscape 3.6.1 was applied for network analysis to identify key targets, and gene enrichment of the targets shared by both YCHD and CHB was performed by DAVID database. The virtual verification of binding abilities between the target protein and the small molecule was finally performed by the Sytems Dock platform. Results: The potentially important targets associated with CHB corresponding to 33 compound components from YCHD included ESR1, CYP1A2, PTGS2, CYP1A1, ABCG2, MMP9. Besides, enriched were the related 8 KEGG pathways (P<0.05) such as ABC transporters, Bile secretion, TNF signaling pathway. Conclusions: This study used network pharmacology method to reveal the characteristics,“multi-component and multi-target and multi-pathway”, of YCHD on CHB treatment, providing thoughts for further research.

Research progress of Yinchenhao Decoction in the treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases worldwide.Non-alcoholic steatohepatitis(NASH)is the most serious type and a turning point in the progression of NAFLD.If not treated actively,NASH will progress to irreversible liver damage such as cirrhosis and hepatocellular carcinoma.At present,there are no specific therapeutic drugs in western medicine.The treatment methods are mainly to improve lifestyle and exercise therapy,to alleviate the symptoms of discomfort,delay the progress of the disease,and improve the quality of life.However,the effect is often not ideal,prone to recurrence,and compliance is relatively poor.Dramatically,traditional Chinese medicine has certain advantages in the treatment of NAFLD.Modern research has confirmed that Yinchenhao Decoction has a good effect on liver-protective and choleretic action and improving liver function.It has significant curative effect on various liver and gallbladder diseases such as acute liver injury and alcoholic liver disease.This article summarized the clinical and basic research of Yinchenhao Decoction in the treatment of NAFLD.We found that Yinchenhao Decoction can enhance the efficiency of NAFLD and improve symptoms such as dizziness,liver pain,hepatosplenomegaly and indigestion.The mechanisms may be related to that Yinchenhao decoction improves the disorder of glucose and lipid metabolism,inflammatory state and liver function.

Mechanism of Yinchenhao decoction in the treatment of jaundice based on network pharmacology

Objective:This study aimed to examine the mechanism of classic ancient prescription of Chinese medicine Yinchenhao decoction in treating jaundice based on network pharmacology.Method:An oral bioavailability of≥30%,a drug likeness of≥0.18,and literature studies were used to screen for Yinchen(Artemisiae scopariae herba),Zhizi(Gardeniae fructus),Dahuang(Rhei radix et rhizome)in the Chinese Medicine System Pharmacology Database and Analysis Platform.The active ingredient was introduced into the PubChem database to collect drug component targets and import into the Uniprot database for gene standardization.The target gene of Yinchen(Artemisiae scopariae herba)was screened via Human Gene Database(GeneCards).Then,use the Cytoscape 3.7.2 software was used for network visualization analysis,and the R3.6.1 software was used for gene ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses.Results:We collected a total of 47 active constituents of classic ancient prescription of Chinese medicine Yinchenhao decoction,of which 17 were related to jaundice;189,9 targets of jaundice were screened,of which 41 were interdigitated with the targets of classic ancient prescription of Chinese medicine Yinchenhao decoction.Gene ontology functional enrichment analysis revealed 111 biological processes,14 cellular components,and 28 molecular functions,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed 34 Kyoto Encyclopedia of Genes and Genomes pathways including hepatocellular carcinoma,PI3K-Akt signaling pathway,HIF-1 signaling pathway,prolactin signaling pathway,and non-alcoholic fatty liver disease.Conclusion:Based on the network pharmacology,the analysis of jaundice and classic ancient prescription of Chinese medicine Yinchenhao decoction provides a novel idea and direction for the study of classic ancient prescription of Chinese medicine Yinchenhao decoction in the treatment of jaundice.

茵陈蒿汤联合还原型谷胱甘肽治疗慢性乙型肝炎临床观察

目的探究茵陈蒿汤联合还原型谷胱甘肽对慢性乙型肝炎(CHB)患者的临床疗效。方法选取2020年5月—2022年5月宜丰县人民医院收治的CHB患者60例,依据不同治疗方式分为两组,观察组采用茵陈蒿汤联合还原型谷胱甘肽治疗,对照组采用还原型谷胱甘肽治疗。比较两组肝功能、生活质量评分、临床疗效、不良反应发生率、肝纤维化指标水平等。结果治疗后,两组总胆红素(TBil)比较,差异无统计学意义(P>0.05);观察组天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)低于对照组(P<0.05);观察组社会、环境、躯体、心理评分高于对照组(P<0.05);观察组的Ⅳ型胶原(Ⅳ-C)、层黏连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、透明质酸(HA)指标均明显低于对照组,差异有统计学意义(P<0.05)。观察组治疗总有效率96.67%(29/30)高于对照组的66.67%(20/30)(P<0.05);观察组不良反应低于对照组(P<0.05)。结论茵陈蒿汤联合还原型谷胱甘肽治疗CHB患者,对提升临床疗效、改善肝纤维化指标水平、提升生活质量的意义重大,同时能够改善肝功能指标,降低不良反应。

基于CiteSpace的茵陈蒿汤研究现状及热点的可视化分析

目的利用文献计量学方法对茵陈蒿汤的相关文献进行可视化分析,探究其研究热点及前沿。方法检索中国知网1992年1月至2022年12月有关茵陈蒿汤研究的相关文献,运用CiteSpace 6.1.R6软件分析作者、研究机构及关键词,并对关键词进行聚类,绘制可视化图谱。结果共纳入856篇文献,发文量总体呈波动上升;纳入的文献中,共涉及764名作者,相关关键词共513个,内容包括茵陈蒿汤的临床运用、实验研究和信号通路探讨等。结论茵陈蒿汤虽为治疗肝病的常用方,但目前比较缺乏有关作用机制、分子水平的研究,未来的研究热点应更多地聚焦在大样本随机对照临床研究和实验研究等方面,为科研人员提供新的方向。

茵陈蒿汤治疗肝胆疾病研究进展及质量标志物预测分析

茵陈蒿汤源于张仲景《伤寒杂病论》一书,是治黄疸第一良方。具有清热、利湿、解毒和退黄等功效。现代药理研究表明,其方有保护肝损伤及抗肝纤维化等保肝利胆作用,临床上以治疗黄疸型肝炎、非酒精性脂肪肝等为主。综述了茵陈蒿汤在化学成分,肝胆疾病的治疗及其药理作用等方面的研究进展。同时,基于中药质量标志物(Q-marker)这一概念中的五原则途径和以现代生物学技术为基础的代谢组学研究、网络药理学等来预测分析茵陈蒿汤质量标志物。提示绿原酸、滨蒿内酯、茵陈色原酮、栀子苷、西红花苷Ⅰ、大黄酸、芦荟大黄素、大黄素甲醚-8-O-β-D-葡萄糖苷可作为该复方的Q-marker,以期为茵陈蒿汤质量控制体系的建立提供科学的参考依据。

茵陈蒿汤治疗热重于湿证阻塞性黄疸患者的临床疗效研究

目的:探讨茵陈蒿汤联合常规治疗对热重于湿证阻塞性黄疸患者的临床疗效。方法:选取2020年6月-2021年12月天津市南开医院收治的热重于湿证阻塞性黄疸(良、恶性胆道梗阻均可)96例,随机分为对照组和治疗组,每组48例,所有患者行手术、内镜取石或置入胆道支架等操作解除梗阻。术后,对照组给予常规治疗(丁二磺酸腺苷蛋氨酸肠溶片),观察组在对照组基础上加用茵陈蒿汤,疗程1周。检测患者黄疸指标[总胆红素(TBIL)、直接胆红素(DBIL)]、肝功能[谷丙转氨酶(ALT)、谷氨酰转移酶(GGT)]、血总胆汁酸(TBA)、尿TBA、中医证候评分、临床疗效变化。结果:与术后第1天比较,两组患者解除胆道梗阻后第7天的TBIL、DBIL、ALT、GGT、血TBA均有所降低(P<0.05),与对照组比较,治疗组降低更明显(P<0.05);两组患者尿TBA、24h尿量均增加(P <0.05),与对照组比较,治疗组增加更加明显(P <0.05)。治疗组中医症状量化评分低于对照组(P <0.05);治疗组总有效率优于对照组(P <0.05)。两组不良反应发生率比较差异无统计学意义(P>0.05)。结论:阻塞性黄疸热重于湿证患者胆道梗阻解除后,给予茵陈蒿汤联合常规治疗可以促进患者胆汁酸排泄,减轻黄疸,保护肝功能,有效改善患者中医临床症状,进而提高患者的临床治疗有效率,耐受性较好。

基于网络药理学和试验验证探讨茵陈蒿汤治疗糖尿病的作用机制

【目的】通过网络药理学、分子对接和试验验证的方法探讨茵陈蒿汤(YCHD)治疗糖尿病(DM)的作用机制。【方法】利用TCMSP、ETCM、UniProt、SwissTargetPrediction数据库及文献查阅等查找YCHD的活性成分和相关作用靶点;利用OMIM、PharmGkb、TTD、DrugBank数据库获取DM的疾病靶点。构建YCHD和DM的蛋白互作(PPI)网络图,对关键作用靶点进行GO功能和KEGG通路富集分析。采用AutoDockTool 1.5.7软件进行分子对接,预测活性成分和核心靶点的结合能。将细胞分为对照组(Control)、模型组(Model)及YCHD含药血清低(YCHD-L)、中(YCHD-M)、高(YCHD-H)剂量组,通过体外细胞试验检测诱导型一氧化氮合酶(iNOS)、环氧化酶2(COX2)、Toll样受体4(TLR4)、核因子κB(NF-κB)p65、白细胞介素-1β(IL1β)、IL6的mRNA表达水平,以及iNOS、COX2、髓样分化因子88(MyD88)、NF-κB p65蛋白表达水平,并对关键通路进行验证。【结果】共获得YCHD活性成分147个,DM疾病靶点486个,YCHD作用于DM的相关靶点基因57个,其中胰岛素(INS)、IL1β、肿瘤坏死因子(TNF)、B细胞中κ轻型多肽基因增强子的核因子1(NFKB1)、信号传导子和转录活化子1(STAT1)、白蛋白(ALB)、TLR4、IL1A、IL10、IL8等为关键靶基因。根据Counts值筛选出GO前十的条目中包含生物过程1条、细胞组分7条、分子功能2条,主要包括RNA聚合酶Ⅱ启动子转录的正调控、内质网膜、质膜、胞外区、核质、胞质溶胶、细胞质、膜的组成部分、相同蛋白质结合和蛋白质结合。KEGG通路富集分析显示,与NOD样受体、NF-κB、Toll样受体等炎症信号通路密切相关。分子对接结果显示,YCHD的活性有效成分与主要靶点具有良好的结合能力。体外试验结果表明,与对照组相比,模型组细胞TLR4、iNOS、COX2、NF-κB p65、IL1β和IL6 mRNA表达水平及iNOS、COX2、MyD88、NF-κB p65蛋白表达水平均显著升高(P<0.05);与模型组相比,YCHD-L、YCHD-M、YCHD-H组细胞iNOS、COX2、IL1β和IL6 mRNA表达水平及iNOS、COX2蛋白表达水平均显著降低(P<0.05),YCHD-M、YCHD-H组细胞TLR4、NF-κB p65 mRNA水平显著降低(P<0.05),YCHD-H组细胞MyD88、NF-κB p65蛋白表达水平显著降低(P<0.05)。【结论】YCHD可能通过多成分、多靶点,调控TLR4、NF-κB等多条炎症信号通路,发挥抗DM的作用。以YCHD-H组对炎症信号通路相关指标的抑制最明显。

中西医结合治疗妊娠期肝内胆汁淤积的效果

目的探讨中西医结合治疗妊娠期肝内胆汁淤积(intrahepatic cholestasis of pregnancy,ICP)的效果及安全性。方法回顾性分析2020年1月至2022年6月杭州师范大学附属医院接受治疗的151例ICP患者的临床资料。按照治疗方案的不同,将所有患者分为对照组(100例)和观察组(51例)。对照组患者给予基础疗法,即熊去氧胆酸胶囊+注射用腺苷蛋氨酸;观察组患者在对照组治疗的基础上,给予茵陈蒿汤加减方煎服,疗程为1周。比较两组患者的实验室血清指标、瘙痒情况、母婴结局及安全性。结果治疗后,两组患者的血清总胆红素、丙氨酸转氨酶、天冬氨酸转氨酶、总胆汁酸水平和瘙痒评分均显著低于本组治疗前,且观察组显著低于对照组(P<0.05)。观察组患者的瘙痒缓解率显著高于对照组,瘙痒控制时间显著短于对照组(P<0.05)。观察组患者的剖宫产、羊水浑浊、产后出血发生率均显著低于对照组,终止妊娠时的孕龄显著高于对照组(P<0.05)。治疗后,两组围产儿的脐动脉收缩期峰值和舒张末期流速比值显著低于本组治疗前,且观察组显著低于对照组(P<0.05)。两组患者治疗过程中均未发生药物过敏反应,也无胎盘早剥或死胎等严重并发症出现。结论相较于单一的西医疗法,中西医结合治疗ICP效果更好,可很大程度改善血清胆汁酸、胆红素和肝酶水平,减轻瘙痒,改善母婴结局,副作用小,具有良好安全性。

茵陈蒿汤对自身免疫性肝炎小鼠肝细胞铁死亡的抑制作用及其机制分析

目的 探讨茵陈蒿汤对自身免疫性肝炎小鼠肝细胞铁死亡的抑制作用及机制。方法 选取SPF级雌性C57BL/6小鼠18只,采用随机数字表法分为正常组、模型组、治疗组,每组6只。模型组和治疗组采用刀豆蛋白A(Con A)尾静脉注射制备自身免疫性肝炎小鼠模型,正常组注射生理盐水。治疗组于造模前14天,给予茵陈蒿汤(4.68 g生药/kg)预防性灌胃治疗,末次灌胃给药后注射Con A。分别检测ALT、AST、IFN-γ、TNF-α、铁离子、GSH、ROS、ATP、MDA水平,计算肝脏指数、脾脏指数,并观察GPX4、SLC7A11的表达;比较各组小鼠肝脏病理组织变化。正态分布的计量资料3组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果 与正常组比较,模型组肝脏指数、脾脏指数、ALT、AST、IFN-γ、TNF-α、铁离子、ROS、MDA水平均升高(P值均<0.05),GSH、ATP含量及GPX4、SLC7A11蛋白表达水平降低(P值均<0.05)。与模型组比较,治疗组肝脏指数、脾脏指数、ALT、AST、IFN-γ、TNF-α、铁离子、ROS、MDA水平均降低(P值均<0.05),GSH、ATP含量及GPX4、SLC7A11蛋白表达水平升高(P值均<0.01)。HE染色结果显示,与正常组比较,模型组小鼠肝脏出现大面积肝细胞变性、坏死、门管区炎细胞聚集,治疗组处理的小鼠肝脏坏死和炎性浸润程度较模型组有所减轻。结论 Con A诱导肝组织损伤可能与铁死亡有关。茵陈蒿汤可以增加SLC7A11/GPX4蛋白的表达水平进而抵抗Con A诱导的肝细胞铁死亡。

胎盘因素对ICP发病的影响及茵陈蒿汤治疗ICP的作用机制

妊娠期肝内胆汁淤积(ICP)是妊娠期常见的肝脏疾病,临床主要表现为母体总胆汁酸水平升高、皮肤瘙痒及胎儿窘迫、早产等。近年来多认为ICP发病与遗传因素、环境因素、女性性激素水平和免疫功能失调等相关。胎盘作为母体与胎儿物质交换场所,发生ICP时,胎盘组织细胞过度凋亡,胎盘功能障碍,导致ICP不良妊娠结局。茵陈蒿汤作为治疗黄疸的经典方剂,可减轻ICP患者瘙痒、黄疸症状,降低血清胆汁酸水平,但其作用机制尚不完全明确。深入研究胎盘因素引发ICP的机制以及茵陈蒿汤治疗ICP的作用机制,可以更加全面地了解ICP,为ICP的治疗提供新方向。

茵陈蒿汤治疗肝纤维化的核心功能成分群以及潜在通路

目的基于网络药理学和体外实验分析验证茵陈蒿汤(YCHD)治疗肝纤维化(HF)的核心功能成分群(CFCG)以及潜在通路。方法在DisGeNET、Genecards、CMGRN和PTHGRN提取了HF的PPI数据,使用Cytoscape 3.9.1构建权重网络。从TCMSP中收集茵陈蒿汤所有化学成分,用PreADMET Web服务器和SwissTargetPrediction选择茵陈蒿汤潜在活性成分和靶点。构建融合模型获取功能效应空间并评估有效蛋白,得到CFCG,再进一步对所有目标进行GO和KEGG通路富集分析。细胞实验:体外培养人肝星状细胞(LX-2),分别设置空白组(不加TGF-β1刺激)、对照组NC(20 ng/mL TGF-β1刺激)和化合物组(0、50、100、200μmol/L),CCK-8实验检测药物敏感性,qPCR实验检测化合物对LX-2中Ⅰ型胶原Α1(COL1A1)的影响,Western blotting实验分析评估化合物在TGF-β1刺激下对LX-2中潜在通路的影响,验证潜在治疗机制。结果分析得到1005个致病基因,茵陈蒿汤潜在活性成分和靶点分别有226个和1529个,核心功能成分群有52个。根据模型计算结果,选取得分最高的乙酸苄酯、香草酸、苯甲酸甲酯、虎杖苷、月桂酸、阿魏酸进行CCK-8验证发现在200μmol/L内无细胞毒性;在qPCR实验中,与TGF-β1组相比苯甲酸甲酯、虎杖苷、月桂酸和阿魏酸能够抑制TGF-β1诱导的LX-2活化。GO和KEGG分析及Western blotting验证发现,这4种成分在200μmol/L浓度时对PI3K、p-PI3K、AKT、p-AKT、ERK、p-ERK、P38 MAPK、p-P38 MAPK有不同程度的抑制。结论茵陈蒿汤抗肝纤维化可能是其中的乙酸苄酯、香草酸、苯甲酸甲酯、虎杖苷、月桂酸、阿魏酸等成分通过抑制PI3K-AKT和MAPK通路实现的。

加味茵陈蒿汤直肠滴入治疗黄疸型病毒性肝炎肝胆湿热证对患者肝功能及炎症指标的影响

目的探讨在黄疸型病毒性肝炎肝胆湿热证中以加味茵陈蒿汤直肠滴入治疗的临床效果,并针对该治疗方法对患者肝功能及炎症指标的影响进行分析。方法回顾性分析2022年1月至2023年2月九江市中医医院收治的80例肝胆湿热型黄疸患者的临床资料,按照不同治疗方案将其分为对照组(40例)与观察组(40例),对照组给予利胆退黄、保肝抗炎、营养支持等对症治疗,观察组在此基础上加用加味茵陈蒿汤直肠滴入治疗,比较两组患者临床疗效及治疗前后肝功能、中医证候积分及炎症指标等情况。结果观察组治疗总有效率高于对照组,差异有统计学意义(P<0.05);治疗后,观察组中医证候(黄疸、发热、恶心呕吐、大便干结、口干及纳呆)评分及炎症指标超敏C反应蛋白(hs-CRP)、肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)水平低于对照组,两组治疗后肝功能指标总胆红素(TBil)、结合胆红素(DBil)、谷丙转氨酶(ALT)、天冬氨酸氨基转移酶(AST)、谷氨酰转肽酶(GGT)及碱性磷酸酶(ALP)指标水平低于本组治疗前,差异有统计学意义(P<0.05);观察组治疗后总胆红素(TBil)、直接胆红素(DBil)、谷氨酰胺转移酶(GGT)指标水平低于对照组,差异有统计学意义(P<0.05)。结论将加味茵陈蒿汤采用直肠滴入的治疗方式能够有效改善黄疸型病毒性肝炎肝胆湿热证患者肝功能,降低其炎症反应,具有较好治疗效果,为临床提供更多有效治疗手段。

茵陈蒿汤调控Nrf-2/HO-1通路对慢性阻塞性肺疾病大鼠气道重塑的影响

目的:探讨茵陈蒿汤调控抗氧化相关转录因子核因子相关因子2(Nrf-2)/亚铁血红素氧化酶1(HO-1)通路对慢性阻塞性肺疾病(COPD)大鼠气道重塑的影响。方法:通过注射脂多糖联合烟熏制备COPD大鼠,造模后随机分为模型组、茵陈蒿汤(4.41 g/kg)组、氨茶碱(2.3 mg/kg)组、茵陈蒿汤+抑制剂(4.41 g/kg茵陈蒿汤+30 mg/kg ML385)组,并以正常大鼠为对照组,检测大鼠肺功能[呼气峰流量(PEF)、第一秒用力呼气容积(FEV1)/用力肺活量(FVC)];评估血清白细胞介素(IL)-1β、IL-6水平及肺组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平;检测肺组织病理学变化以及转化生长因子(TGF-β)、结缔组织生长因子(CTGF)阳性表达、金属基质蛋白酶(MMP)-2 mRNA、MMP-9 mRNA表达、Nrf-2、HO-1蛋白表达。结果:模型组FEV1/FVC、PEF、肺组织SOD、GSH-Px水平、Nrf-2、HO-1蛋白表达较对照组降低,血清IL-1β、IL-6、病理评分、肺组织TGF-β、CTGF、MMP-2 mRNA、MMP-9 mRNA表达增加(均P<0.05);茵陈蒿汤或氨茶碱治疗后,FEV1/FVC、PEF、肺组织SOD、GSH-Px水平、Nrf-2、HO-1蛋白表达较模型组增加,血清IL-1β、IL-6、病理评分、肺组织TGF-β、CTGF、MMP-2 mRNA、MMP-9 mRNA表达显著降低(均P<0.05);茵陈蒿汤联合ML385治疗后,FEV1/FVC、PEF、肺组织SOD、GSH-Px水平、Nrf-2、HO-1蛋白表达较茵陈蒿汤组降低,血清IL-1β、IL-6、病理评分、肺组织TGF-β、CTGF、MMP-2 mRNA、MMP-9 mRNA表达增加(均P<0.05)。结论:茵陈蒿汤可通过调控Nrf-2/HO-1通路改善COPD大鼠气道重塑。

加味茵陈蒿汤辅助肝动脉化疗栓塞术对中晚期原发性肝癌患者中医证候和Janus激酶2/信号转导与转录激活因子3信号通路的影响

目的观察加味茵陈蒿汤辅助肝动脉化疗栓塞术(TACE)对中晚期原发性肝癌患者中医证候、Janus激酶2/信号转导与转录激活因子3(JAK2/STAT3)信号通路的影响。方法选取2020年6月至2022年6月福建省泉州滨海医院肿瘤科107例中晚期原发性肝癌患者为研究对象,按照简单随机化法分为对照组(n=53)和治疗组(n=54)。对照组予TACE,治疗组在对照组基础上加加味茵陈蒿汤治疗。统计2组实体瘤疗效、毒副反应及治疗前后中医证候(胁痛、痞块、腹胀)积分、JAK2/STAT3信号通路mRNA表达及其下游靶基因[B细胞淋巴瘤-XL基因(Bcl-XL)、细胞周期蛋白D1(Cyclin D1)、人髓细胞增生原癌基因(c-Myc)]蛋白表达、肝功能指标[天冬氨酸氨基转移酶(AST)、总胆红素(TBiL)、丙氨酸氨基转移酶(ALT)]。结果治疗组疾病控制率为79.63%(43/54),对照组疾病控制率为58.49%(31/53),治疗组疾病控制率高于对照组(P<0.05)。治疗后2组胁痛、痞块、腹胀评分,外周血JAK2、STAT3 mRNA表达,Bcl-XL、Cyclin D1、c-Myc蛋白表达,AST、TBiL、ALT水平均较本组治疗前降低(P<0.05),且治疗组均低于对照组(P<0.05)。治疗组Ⅰ~Ⅱ级肝肾功能异常发生率低于对照组(P<0.05)。结论加味茵陈蒿汤辅助TACE对中晚期原发性肝癌患者症状、肝功能及疗效的改善具有积极作用,可能机制与下调JAK2/STAT3信号通路有关。

中药联合常规治疗在梗阻性黄疸患者中的应用效果

目的:分析中药联合常规治疗在梗阻性黄疸患者中的应用效果。方法:选取2022年1月—2023年7月天津市中西医结合医院收治的梗阻性黄疸患者94例作为研究对象,随机分为常规组与联合组,各47例。常规组实施常规治疗,联合组在常规组基础上给予中药治疗。比较两组中医证候积分、治疗效果、肝功能指标[天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)]。结果:治疗前,两组中医证候积分比较,差异无统计学意义(P>0.05);治疗后,两组中医证候积分下降,联合组低于常规组,差异有统计学意义(P<0.05)。联合组治疗总有效率高于常规组,差异有统计学意义(P=0.035)。治疗前,两组AST、ALT水平比较,差异无统计学意义(P>0.05);治疗后,两组AST、ALT下降,联合组低于常规组,差异有统计学意义(P<0.05)。结论:中药联合常规治疗在梗阻性黄疸疾病中的应用效果显著,能够减轻临床症状,改善肝功能指标。

肝胆湿热黄疸治疗思路浅析

文章通过撷取临床验案六则:慢性乙型病毒性肝炎案、乙型肝炎后肝硬化失代偿期伴肝衰竭案、乙型肝炎肝硬化后伴肝癌案、药物性肝损害案、酒精性肝硬化失代偿期伴肝衰竭案、酒精性肝损害伴肝衰竭案等,逐一分析总结治疗黄疸的辨病辨证过程以及治疗用药思路;医案力求反映临床原貌,结合辅助检查结果客观反映治疗效果,并以按语形式总结治疗心得体会。纵观验案,饮食不节,嗜食肥甘厚味,过量饮酒,为黄疸的常见诱发因素;病机抓住湿,治疗上利湿与健脾并举,以期“培土制水”;用药顾护脾胃,“正气内存,邪不可干”,维护好后天之本;淡渗利湿之药,中病即止。治疗思路力求简单明了,用药精简对症,临床上期望达到执简驭繁,收到立竿见影之效。