To explore the mechanism of Dahuang Lingxian Formula in relieving inflammatory response of bile duct cells based on IL-6/JAK/STAT3 signaling pathway

Objective:To explore the mechanism of action of Dahuang Lingxian Formula in alleviating the inflammatory response of bile duct cells in LPS-induced intrahepatic bile duct inflammation model rats based on IL-6/JAK/STAT3 signaling pathway.Methods:Fifty SD rats were randomly divided into five groups,blank group,model group,choling tablets(0.5 g/kg),and low and high concentration groups(2.4 g/kg and 4.8 g/kg)of Dahuang Lingxian Formula,ten rats in each group.Except for the blank group,the rats in each group were injected with 1.25 mg/kg LPS at the common bile duct at one time to construct an animal model of intrahepatic bile duct infection.After gavage on day 8,liver tissues were taken from rats at the hepatic hilum,and the histopathological changes of the hepatic hilum and biliary tree were observed by HE staining.The expression levels of serum glutamic alanine transaminase(ALT),glutamic oxalacetic transaminase(AST),malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by biochemical method.The expression levels of interleukin 6(IL-6),Janus protein tyrosine kinase 2(JAK2),signal transducer and activator of transcription 3(STAT3)in rat serum were measured by enzyme-linked immunosorbent assay(ELISA).Protein immunoblotting(WB)and real-time fluorescence quantitative PCR(RT-qPCR)were used to detect the expression levels of IL-6,JAK2,STAT3 protein and mRNA in biliary tree tissues.Results:①Compared with the blank group,the structures such as interlobular bile ducts in the hepatic sinusoids and portal duct area of the model rats were destroyed,and inflammatory cells infiltrated around them.The expression of ALT,AST,MDA,IL-6,JAK2 and STAT3 in the serum increased significantly,the expression level of SOD decreased,and the expression levels of IL-6,JAK2 and STAT3 proteins and mRNA increased.②Compared with the model group,the degree of liver pathological damage in rats in the Chiling Ning tablet group and the low and high concentration groups of Dahuang Lingxian Formula were improved,which could significantly reduce the expression levels of ALT,AST,MDA,IL-6,JAK2,STAT3 and up-regulate SOD in serum,and down-regulate the expression of IL-6,JAK2,STAT3 protein and mRNA,with the best effect in the high concentration group of Dahuang Lingxian Formula.③Compared with the choling tablet group,the rats in the low and high concentration groups of Dahuang Lingxian Formula tended to normalize the degree of liver pathological damage,without obvious inflammatory cell infiltration,and the expression levels of ALT,AST,MDA,IL-6,JAK2,STAT3 and the expression levels of IL-6,JAK2,STAT3 protein and mRNA in serum were reduced,and the expression levels of SOD were increased,with the best effect of Dahuang Lingxian Formula The treatment effect was best in the high concentration group.Conclusion:The mechanism may be related to the down-regulation of IL-6/JAK/STAT3 signaling pathway activation,and the best therapeutic effect was achieved by the high concentration group of Dahuang Lingxian Formula.

Effects of Dahuang( Rhubarb) Retention Enema on Leukocyte Interleukin-6,High Sentive C Reactive Protein and Endotoxin in Patients with Acute Pancreatitis

[Objectives] To observe the clinical effect of Dahuang( Rhubarb) retention enema on patients with severe acute pancreatitis and its influences on leukocyte interleukin 6( IL-6),high sentive C reactive protein( hs-CRP) and endotoxin. [Methods]86 cases of acute pancreatitis were randomly divided into the control group( 43 cases) and the treatment group( 43 cases). The control group was given saline enema and routine treatment of western medicine,while the treatment group was treated with Dahuang( Rhubarb) decoction retention enema and routine treatment,2 times/d. After 7 days of treatment,two groups of clinical curative effects were compared. And changes of IL-6,hs-CRP,endotoxin and amylase levels before and after treatment in two groups were compared. [Results] Abdominal pain,abdominal distension,exhaust defecation,bowel sounds in treatment group patients were obviously improved. After treatment,the decline levels of serum IL-6,hsCRP,endotoxin and amylase in the treatment group were significantly better than those in the control group. [Conclusions] Dahuang( Rhubarb) retention enema can significantly improve the clinical curative effect of severe acute pancreatitis,and its mechanism may be related to the inhibition of inflammatory reaction.

Dahuang Fuzi decoction reduces inflammation levels and alleviates intestinal mucosal barrier damage in septic rats

Objective:To investigate the protective effect of Dahuang Fuzi Decoction(DHFZD),a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods:Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups:normal control group(NCG,n?10),model control group(MCG,n?15)and DHFZD-treated group(DHFZDG,n?15).NCG rats were sham operated on and used as the controls,whereas MCG and DHFZDG rats were used to replicate the rat sepsis model using cecal ligation and puncture(CLP).The DHFZDG rats received DHFZD by gavage(4.5 mg/g of body weight)2 h prior to CLP and after its successful induction,while the NCG and MCG rats received equivalent amounts of sterilized water by gavage.All rat groups were starved and had free access to water.At 24 h post-experimental set up,the mortality of rats in each group was recorded,and peritoneal inflammation assessment and pathological changes related to the intestinal mucosal injury index(IMII)in the surviving rats were evaluated.D-lactic acid,tumor necrosis factor(TNF)-a,interleukin(IL)-6 and IL-10 peripheral blood concentrations,along with secretory immunoglobulin A(sIgA)in the intestinal mucosa were evaluated by enzyme-linked immunosorbent assays.Gut microbes were detected using 16S rRNA gene sequencing.Results:DHFZD reduced sepsis-related mortality in the rats.Moreover,it alleviated peritoneal inflammation and pathological changes according to the IMII.DHFZD reduced serum procalcitonin,TNF-a and IL-6 concentrations,but not the IL-10 concentration.It also reduced serum D-lactic acid and increased sIgA concentrations in intestinal mucosa.Notably,DHFZDG restored gut microbiota diversity and regulated the decrease in Bacteroidetes induced by sepsis,compared with the MCG rats.Conclusion:DHFZDG may play a protective role in sepsis by alleviating sepsis-induced inflammation and gut barrier damage in rats.

Study on multi-target mechanism of Radix et Rhizoma Rhei (Dahuang) and Semen Persicae (Taoren) on adhesion intestinal obstruction based on network pharmacology

Objective: To explore the mechanism of action of Radix et Rhizoma Rhei (Dahuang)(RERR) and Semen Persicae (Taoren)(SP) on adhesive intestinal obstruction (AIO). Methods: The main targets of the active ingredients of RERR and SP were filtered based on the traditional Chinese medicine system pharmacology analysis platform. Cytoscape 3.2.1 was applied to build the ingredient-target network of RERR and SP for AIO. Results: Fifteen active components were predicted from the RERR and SP herb pair, such as aloe-emodin, catechin, rhein, gibberellin (GA) 119, GA120 and GA121. These components were applied to 59 targets mainly involved in many biological processes such as signal transduction, anti-apoptosis, and inflammatory response involved in activating the immune effect. Conclusion: This study proposes the system pharmacology method and identifies the potent combination therapeutic mechanism of RERR and SP for AIO. This strategy will provide a new insight to the study of herb combinations.

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-

Experimental Study on the Treatment of Gallbladder Distention by Dahuang Lingxian Prescription

Objective: To investigate the mechanism of inhibiting the secretion of “lithogenic bile” and treating gallbladder distention with the TCM prescription Dahuang Lingxian. Methods: Forty SPF-grade SD male mice were randomly divided into blank control group, model group, ursodeoxycholic acid group and TCM group, 10 mice in each group. The blank control group was kept normally, and the model group, ursodeoxycholic acid group and TCM group were established as gallbladder distention models. The blank control group and the model group were given 1.5 ml of saline by gavage daily;the ursodeoxycholic acid group was given 100 mg/kg/d of a mixture of saline and ursodeoxycholic acid capsules by gavage daily;the TCM group was given 39 g/kg/d of aqueous decoction of Dahuang Lingxian Prescription by gavage daily. After 6 weeks of continuous intervention, all mice were executed and the lithogenesis rate, ultrastructure and mRNA expression were observed. Results: The lithogenesis rate of mice in the TCM group was significantly reduced (P β1/Smads pathway was significantly improved (P < 0.05), which could achieve the same therapeutic effect as ursodeoxycholic acid capsules. Conclusion: Dahuang Lingxian Prescription can reduce the secretion of “lithogenic bile” by inhibiting the inflammatory reaction and fibrosis of biliary system. Dahuang Lingxian Prescription has certain advantages in the treatment of gallbladder distention.

Effects of LPS-induced cholangitis on the cytoskeleton morphology of bile duct epithelium and the intervention mechanism of Dahuang Lingxian formula for these changes

Objective:To observe the effect of lipopolysaccharide(LPS)on cytoskeleton and the effect of Dahuang Lingxianfang on nF-KB/MAPK signaling pathway.Methods:Biliary epithelial cells of each group were stained with photolipin fluorescent staining,and the arrangement of cytoskeleton was observed under laser confocal microscope.Western blotting was used to detect the expression of f-actin.Results:After LPS intervention,the biliary epithelial cells showed nuclear shrinkage or damage,and the skeleton was broken or lumped.The cytoskeleton was partially repaired after the intervention of pathway blocking preparation combined with RHUbarb Lingxianfang.All the other groups had different degree of cytoskeleton fracture.Compared with normal group,the expression of F-actin protein in LPS group was decreased(P<0.05);Compared with LPS group,the expression of F-actin in LPS+TCM group,LPS+PDTC+TCM group,LPS+SB203580+TCM group and LPS+PDTC+SB203580+TCM group was significantly increased(P<0.05);Compared with traditional Chinese medicine group,the expression of F-actin in LPS+PDTC+traditional Chinese medicine group,LPS+SB203580+traditional Chinese medicine group and LPS+PDTC+SB203580+traditional Chinese medicine group had no significant difference(P>0.05).Conclusion:RHUbarb Lingxianfang can restore the sequence of biliary epithelial cytoskeleton and protect its microfilament structure under inflammation,and its mechanism may be related to the regulation of NF-KB/MAPK signaling pathway.

Clinical Study on the Retention Enema with Modified Dahuang Mudan Decoction in Treating Lower-Jiao Obstruction Syndrome Caused by Severe Pneumonia Complicated with Heart Failure

[Objectives]To treat patients with Lower-Jiao Obstruction Syndrome caused by severe pneumonia complicated with heart failure using the retention enema with Modified Dahuang Mudan Decoction,and to observe the effect and safety of this treatment on inflammatory indicators,cardiac function,gastrointestinal function and multiple organ failure in patients with Lower-Jiao(lower energizer)Obstruction Syndrome caused by severe pneumonia complicated with heart failure.[Methods]54 patients with Lower-Jiao Obstruction Syndrome caused by severe pneumonia complicated with heart failure diagnosed in Nanchong Chinese Medicine Hospital from January 2020 to December 2021 were randomly divided into experimental group(n=27)and control group(n=27).The control group was given conventional treatment combined with 0.9%sodium chloride injection(100 mL)+glycerine enema(40 mL).The treatment group was treated with Modified Dahuang Mudan Decoction on the basis of conventional treatment for 7 d.The efficacy indicators and adverse events such as white blood count(WBC),C-reactive protein(CRP),procalcitonin(PCT),N-terminal pro-brain natriuretic peptide(NT-proBNP),Lausanne Intestinal Failure Estimation(LIFE)and multiple organ dysfunction score(MODS)were observed.[Results](i)There was no significant difference in WBC,PCT,CRP and NT-proBNP between the two groups before treatment.All indicators after treatment were significantly lower than those before treatment in both groups(P<0.05).The levels of WBC,PCT and CRP in the treatment group were lower than those in the control group after treatment(P<0.05),and there was no significant difference in NT-proBNP between the two groups after treatment(P>0.05),but the difference in NT-proBNP before and after treatment in the treatment group was higher than that in the control group.(ii)The LIFE of the two groups decreased significantly after treatment,and the improvement of LIFE of the treatment group was better than that of the control group(P<0.05).(iii)The MODS of the two groups decreased significantly after treatment(P<0.05),and the degree of decrease after treatment in the treatment group was higher than that in the control group(P<0.05).(iv)There was no significant difference in all-cause mortality between the two groups(P>0.05).(v)No serious adverse events were found in both groups during the treatment period.[Conclusions]The conventional treatment,combined with the retention enema with Modified Dahuang Mudan Decoction could further reduce the inflammatory indicators,improve cardiac function,improve intestinal function and organ function,and the safety was good.

Effect of Dahuang Zhechong pill combined with antiviral therapy on serum virus replication indexes as well as immunity and inflammation indexes in patients with chronic hepatitis B cirrhosis

Objective:To study the effect of Dahuang Zhechong pill combined with antiviral therapy on serum virus replication indexes as well as immunity and inflammation indexes in patients with chronic hepatitis B cirrhosis.Methods: A total of 104 patients with chronic hepatitis B cirrhosis who were treated in our hospital between May 2013 and April 2016 were selected and randomly divided into combined treatment group and western medicine treatment group who accepted Dahuang Zhechong pill combined with entecavir treatment and entecavir monotherapy respectively. Before and after treatment, the HBV-DNA loads, liver fibrosis index and immune cell levels as well as inflammatory cytokine levels were determined.Results:HBV-DNA loads of both groups of patients at 48 weeks after treatment were significantly lower than those before treatment, and the HBV-DNA loads were not significantly different between the two groups after treatment;serum HA, LN, PC-III, IV-C, IL-15, IL-16 and TGF-β1 levels as well as peripheral blood Treg cell levels of both groups at 24 weeks and 48 weeks after treatment were significantly lower than those before treatment while peripheral blood NK cell levels were higher than those before treatment, and serum HA, LN, PC-III, IV-C, IL-15, IL-16 and TGF-β1 levels as well as peripheral blood Treg cell levels of combined treatment group were significantly lower than those of western medicine treatment group while peripheral blood NK cell levels were higher than those of western medicine treatment group. Conclusion:Dahuang Zhechong pill combined with antiviral treatment of chronic hepatitis B cirrhosis can regulate the immune response and inflammatory reaction without affecting the inhibiting effect of antiviral drugs on viral replication.

Differential metabolite analysis of the pharmacodynamic differences between different ratios of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae) herb pair

OBJECTIVE: To explore the material basis of the difference of efficacy of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae)(DT) drugs with different proportions. METHODS: Samples of different ratios of Dahuang(Radix et Rhizoma Rhei Palnati, DH) to Taoren(Semen Persicae, TR)(Group A 1∶1, B 2∶3, C 3∶2) were analyzed based on gas chromatography time-of-flight mass spectrometry untargeted metabolomics technique. RESULTS: A total of 240 primary metabolites were detected. Forty-one differential metabolites involved nine differential metabolic pathways, of which four were closely related to the efficacy of DT in the treatment of heat and blood stasis syndrome. These pathways included the biosynthesis of amino acid(phenylalanine tyrosine and tryptophan), flavonoids, unsaturated fatty acids, and the glycolysis/glycogenesis pathway. CONCLUSION: There are significant differences in the efficacy of different ratios of DT drugs, and their optimal ratio for the treatment of heat and blood stasis syndrome should be 1∶1.

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.

大黄牡丹汤灌肠联合西药治疗急性胰腺炎临床研究

目的:观察大黄牡丹汤灌肠联合西药治疗急性胰腺炎的临床疗效。方法:采用随机数字表法将144例急性胰腺炎患者分为对照组、治疗组各72例。对照组给予乌司他丁联合生长抑素治疗,治疗组在对照组基础上加用大黄牡丹汤灌肠治疗,2组连续治疗10 d。比较2组临床疗效、临床症状消失时间、不良反应发生率;比较2组治疗前后中医证候积分、血清淀粉酶、脂肪酶、炎症因子水平及外周血T淋巴细胞指标(Th1、Th2、Th17、Treg、Th1/Th2、Th17/Treg)。结果:治疗后,治疗组总有效率98.61%,高于对照组88.89%(P<0.05);治疗组腹胀症状消失时间、腹痛症状消失时间、腹膜刺激征症状消失时间均短于对照组(P<0.05)。治疗后,2组中医证候积分、血清淀粉酶、脂肪酶、干扰素-γ(IFN-γ)、白细胞介素(IL)-17、外周血Th1、Th17水平及Th1/Th2、Th17/Treg均较治疗前降低(P<0.05);治疗组治疗后上述指标均低于对照组(P<0.05)。治疗后,2组血清IL-4、转化生长因子-β(TGF-β)水平及外周血Th2、Treg水平均较治疗前升高(P<0.05);治疗组治疗后血清IL-4、TGF-β水平及外周血Th2、Treg水平高于对照组(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:大黄牡丹汤灌肠联合西药治疗急性胰腺炎,临床疗效显著,能够调节患者Th1/Th2、Th17/Treg细胞平衡,减轻炎症反应,安全性较高。

大黄[庶虫]虫丸临床应用及实验研究进展

大黄[庶虫]虫丸为张仲景治疗虚劳干血的有效方剂。该方是在抵挡汤的基础上加苦杏仁、黄芩、地黄、白芍等8味中药组成,具有活血破瘀、缓中补虚之功,即峻药丸服,以缓攻瘀血,瘀血去则新血生,最终达扶正不留瘀、祛瘀不伤正的目的。适用于虚劳后期、因虚致瘀之证,故此方兼具扶正与祛邪双重功效。临床运用方面,单用大黄[庶虫]虫丸治疗相关疾病的报道偏少,多以其加减方或联合其他方剂或联合西药,治疗肝、心、肺、肾、妇科、男科等各类疾病。实验研究方面,大黄[庶虫]虫丸具有抗炎、抗纤维化,改善血糖、改善血脂、改善血管功能,改善微循环等作用,多针对某一具体疾病探讨其作用、机制,故其物质基础研究相对薄弱。通过查阅近10年大黄[庶虫]虫丸临床应用及实验研究情况,对其临床应用及实验研究进展进行归纳总结,为大黄[庶虫]虫丸深入研究、运用提供参考。

国医大师张志远先生大黄方药解析

运用中医各家学说名医研究方法,以国医大师张志远先生大黄药性研究为例,收集张志远先生大黄药性相关论述,从药物溯源、功用考辨、疑难病证治疗方面,从大黄化食辨、上焦病忌大黄辨、破血止血辨中进一步研究大黄功用,论述大黄在虚劳、郁证、狂证治疗中的独特价值,从中医文献中考证解析大黄作用机理,从中医各家学说学科角度重新认识理解张志远先生理论渊源与学术创新,为继承发扬国医大师学术思想服务。

大黄蛰虫丸加减联合奥拉帕利治疗乳腺癌基因突变型卵巢癌

目的研究大黄蛰虫丸加减联合奥拉帕利治疗乳腺癌基因(breast cancergene,BRCA)突变型卵巢癌的疗效及对癌胚抗原(car-cinoembryonic antigen,CEA)、糖类抗原125(carbohydrate antigen 125,CA125)、糖类抗原199(carbohydrate antigen 199,CA199)水平的影响。方法纳入2021年2月至2023年2月在河南中医药大学第三附属医院进行手术治疗的98例卵巢癌患者的临床资料,根据治疗方式将患者分为对照组(n=49)和观察组(n=49),对照组采用奥拉帕利进行干预,观察组采用大黄蛰虫丸加减联合奥拉帕利进行干预,观察两组治疗前后临床疗效、肿瘤标志物CEA、CA125、CA199水平和药物不良反应。结果治疗后观察组CEA、CA125、CA199水平低于对照组(P<0.05);观察组治疗期间的恶心、肝肾功能异常、疼痛发生率均低于对照组(P<0.05);治疗前两组中医症候(小腹胀痛、纳差、面色晦暗)评分差异无统计学意义(P>0.05);治疗后,两组小腹胀痛、纳差、面色晦暗评分均降低,且观察组评分低于对照组(P<0.05);观察组西医治疗有效率(83.67%)高于对照组(55.10%)(P<0.05);对照组中医治疗有效率(53.06%)低于观察组(83.67%)(P<0.05)。结论大黄蛰虫丸加减联合奥拉帕利治疗BRCA突变型乳腺癌能够起到提高临床疗效、减少药物不良反应的作用。

大黄䗪虫丸联合戈舍瑞林治疗子宫内膜异位症临床观察

目的探讨大黄䗪虫丸联合戈舍瑞林治疗子宫内膜异位症的临床效果及对患者生活质量的影响。方法选择在江西省妇幼保健院住院行腹腔镜手术的子宫内膜异位症患者随机分为两组,各60例。对照组予醋酸戈舍瑞林缓释植入剂,研究组在此基础上予大黄䗪虫丸,观察两组性激素水平、视觉模拟量表(VAS)评分、生存质量评价量表(SF-36)评分。结果治疗后,两组性激素水平及VAS评分均降低、SF-36评分均提高,且相对于对照组,研究组各指标改善情况更明显(P<0.05),患者生活质量得到明显改善。结论大黄䗪虫丸联合戈舍瑞林应用于子宫内膜异位症患者,存在相互补充作用,能够明显改善其疼痛症状,提高生活质量,彰显了中西医药结合的综合治疗优势,临床取得了较为满意的效果,值得推广应用。

中西医结合治疗急性阑尾炎临床观察

目的分析中西医结合治疗急性阑尾炎的效果。方法选择2020年6月—2022年12月住院的急性阑尾炎患者130例,根据患者意愿及随机的方法,分为对照组和观察组,各65例;对照组给予西药抗感染治疗,观察组在对照组的基础上加用中药内服、隔物灸和腕踝针治疗。10 d后观察两组症状缓解时间及疗效。结果治疗后,观察组的临床症状缓解时间短于对照组(P<0.05);观察组的总有效率为100.00%(65/65),高于对照组的89.23%(58/65)(P<0.05)。结论中西医结合治疗急性阑尾炎的效果好,可以较快改善患者的临床症状,值得推广。

大黄蛰虫丸调节IL-1β/NF-κB/NLRP3信号通路对动脉粥样硬化大鼠主动脉炎性损伤的影响

目的 探讨大黄蛰虫丸调节IL-1β/NF-κB/NLRP3信号通路对动脉粥样硬化(AS)大鼠主动脉炎性损伤的影响。方法 将40只大鼠分为正常对照组(NS)、模型组、地奥心血康干预组(阳性组)及大黄蛰虫丸干预组(大黄蛰虫丸组),每组各10只。除正常组外,余下3组小鼠均构建AS模型。应用油红染色对主动脉病理切片情况进行观察,采用EILSA法检测血清脂质水平[甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)]、血清炎症指标(IL-6、IL-1β、TNF-α水平);应用流式细胞术对外周血Th17/Treg细胞水平进行检测,并通过RT-qPCR法和Western blot分别检测IL-1β/NF-κB/NLRP3信号通路mRNA和蛋白表达水平,并计算AI指数。结果 除NC组大鼠以外,其他各组大鼠动脉组织中均出现内膜增厚、斑块沉积和不连续、大量炎症细胞浸润等现象;其中模型组动脉组织损伤现象最为显著,阳性组和大黄蛰虫丸组较模型组明显改善,动脉组织结构情况与NC组相近。模型组血清TC[(9.82±1.46)mmol/L]、TG[(9.82±1.46)mmol/L]、LDL-C[(2.93±0.22)mmol/L]、IL-6[(97.65±9.11)ng/L]、TNF-α[(93.21±11.17)ng/L]水平及外周血Th17[(3.56±0.34)%]、Treg细胞[(4.41±0.38)%]水平高于NC组[分别为(3.71±0.57)mmol/L、(6.47±0.92)mmol/L、(0.94±0.15)mmol/L、(16.52±2.76)ng/L、(5.45±0.84)ng/L、(1.83±0.16)%、(7.72±0.73)%](均P<0.05),HDL-C水平[(2.92±0.31)mmol/L]低于NC组[(0.95±0.08)mmol/L](P<0.05);与模型组相比,大黄蜇虫丸组和阳性组血清TC[分别为(3.92±0.72)mmol/L、(3.71±0.65)mmol/L]、TG[分别为(6.71±0.83)mmol/L、(6.83±0.72)mmol/L]、LDL-C[分别为(1.15±0.11)mmol/L、(1.11±0.13)mmol/L]、IL-6[分别为(19.83±2.55)ng/L、(18.51±3.72)ng/L]、TNF-α[分别为(17.08±1.72)ng/L、(15.92±1.56)ng/L]水平及外周血Th17[分别为(2.11±0.25)%、(2.06±0.22)%]、Treg细胞[分别为(7.45±0.76)%、(7.31±0.72)%]水平偏低,HDL-C偏高[分别为(2.18±0.72)mmol/L、(2.23±0.61)mmol/L],趋近于NC组(均P<0.05)。与NC组AI指数(0.35±0.08)比较,模型组、阳性组和大黄蛰虫丸组(分别为9.71±2.04、1.21±0.15、0.83±0.17)均明显升高(均P<0.05),其中阳性组和大黄蛰虫丸组AI指数低于模型组(均P<0.05)。模型组大鼠的IL-6、TNF-α水平和外周血IL-1β、NF-κB、NLRP3 mRNA和信号通路蛋白表达水平均较NC组、阳性组和大黄蛰虫组明显偏高(均P<0.05)。结论 大黄蛰虫丸对动脉粥样硬化大鼠主动脉的炎性损伤可能具有明显的改善作用,可能是通过抑制IL-1β/NF-κB/NLRP3信号通路来实现治疗效果。

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。

大黄灵仙方调控胆管细胞炎症的作用及机制研究

目的 观察大黄灵仙方调控白细胞介素-1受体相关激酶(interleukin-1 receptor-associated kinase 1,IRAK)-1和IRAK-4以及成纤维生长因子-3激活酶1MAP3K7结合蛋白2(TGF-3 activator 1 map3k7-binding protein 2,TAB2)的表达水平,探讨其缓解胆管细胞炎症的作用机制,为预防肝胆管结石的形成及术后复发提供理论依据。方法 将45只SPF级健康雄性SD大鼠随机分为9组,空白组、模型组、大黄灵仙颗粒组、激活核转录因子κB(nuclear factor kappa-B,NF-κB)阻断剂组、p38丝裂活化蛋白激酶(mitogen-activated protein kinase, MAPK)阻断剂组、NF-κB阻断剂+p38MAPK阻断剂组、NF-κB阻断剂+大黄灵仙颗粒组、p38MAPK阻断剂+大黄灵仙颗粒组、NF-κB阻断剂+p38MAPK阻断剂+大黄灵仙颗粒组,每组大鼠5只。除空白组以外,其余各组大鼠于胆总管处一次性注射5 mg/kg内毒素脂多糖以构建肝内胆管感染动物模型。第7天灌胃结束后取材,取大鼠完整胆管树组织,采用蛋白免疫印迹法和实时荧光定量PCR检测IRAK-1、IRAK-4、TAB2蛋白及mRNA表达量。结果 (1)与空白组比较,模型组IRAK-1、IRAK-4、TAB2蛋白及mRNA表达量升高(P<0.05);(2)与模型组比较,大黄灵仙颗粒组、NF-κB阻断剂组、p38MAPK阻断剂组、NF-κB阻断剂+p38MAPK阻断剂组、NF-κB阻断剂+大黄灵仙颗粒组、IRAK-1、IRAK-4、TAB2的蛋白及mRNA表达量降低(P<0.05),NF-κB阻断剂+p38MAPK阻断剂+大黄灵仙颗粒组IRAK-1、IRAK-4、TAB2蛋白及TAB2 mRNA表达量均显著下降(P<0.05);(3)与大黄灵仙颗粒组比较,NF-κB阻断剂+大黄灵仙颗粒组、NF-κB阻断剂+p38MAPK阻断剂+大黄灵仙颗粒组IRAK-1、IRAK-4、TAB2的蛋白表达量和NF-κB阻断剂+p38MAPK阻断剂组的IRAK-1、IRAK-4、TAB2 mRNA表达量均下降(P<0.05)。结论 大黄灵仙方可缓解内毒素脂多糖诱导的大鼠胆管炎症反应,抑制炎症因子的异常表达,促使胆道恢复至非炎症状态,从而达到预防肝胆管结石的形成及术后复发的目的,其作用机制可能与抑制TLR4/NF-κB/MAPK信号通路下游IRAK-1、IRAK-4和TAB2因子的活化有关。