Mechanism of Gegen Qinlian Decoction in Treating Type 2 Diabetes Mellitus Complicated with NAFLD Based on Network Pharmacology

[Objectives]To explore the mechanism of Gegen Qinlian Decoction in treating type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)by analyzing the effective components of Gegen Qinlian Decoction.[Methods]TCMSP database was used to analyze the active components of Gegen Qinlian Decoction,and pubchem and Swiss ADME databases were also used to predict drug targets,extract T2DM complicated with NAFLD targets from OMIM and Genecards databases.Venny plot was drawn to obtain intersection targets,and finally Cytoscape was used to make core target maps and drug-target-disease network maps.Using DAVID and Metascape database to analyze the intersection targets,the gene ontology information of Go and KEGG was obtained.Microbial informatics technology was used to visualize GO,and Cytoscape was used to make drug-target-disease network map-enrichment pathway map.[Results]The network pharmacological analysis showed that Gegen Qinlian Decoction acted on the key targets of type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease,such as ALB and ALT1,through many components,and achieved the purpose of treating this disease.The chemical constituents of the drug include formononetin,5-hydroxyisomucronulatol-2,5-2-O-glucoside,cholesteryl laurate,isoliquiritigenin,etc.[Conclusions]This study provides a new idea and theoretical support for future drug research and clinical practice.

Administration of modified Gegen Qinlian decoction for hemorrhagic chronic radiation proctitis: A case report and review of literature

BACKGROUND Hemorrhagic chronic radiation proctitis(CRP) is a common late complication of irradiation of the pelvis and seriously impairs life quality. There is no standard treatment for hemorrhagic CRP. Medical treatment, interventional treatment, and surgery are available, but they are limited in their applications due to nondefinite efficacy or side effects. Chinese herbal medicine(CHM), as a complementary or alternative therapy, may provide another option for hemorrhagic CRP treatment.CASE SUMMARY A 51-year-old woman with cervical cancer received intensity-modulated radiation therapy and brachytherapy with a total dose of 93 Gy fifteen days after hysterectomy and bilateral adnexectomy. She received six additional cycles of chemotherapy with carboplatin and paclitaxel. Nine months after radiotherapy treatment, she mainly complained of 5-6 times diarrhea daily and bloody purulent stools for over 10 d. After colonoscopy examinations, she was diagnosed with hemorrhagic CRP with a giant ulcer. After assessment, she received CHM treatment. The specific regimen was 150 mL of modified Gegen Qinlian decoction(GQD) used as a retention enema for 1 mo, followed by replacement with oral administration of 150 mL of modified GQD three times per day for 5 mo. After the whole treatment, her diarrhea reduced to 1-2 times a day. Her rectal tenesmus and mild pain in lower abdomen disappeared. Both colonoscopy and magnetic resonance imaging confirmed its significant improvement. During treatment,there were no side effects, such as liver and renal function damage.CONCLUSION Modified GQD may be another effective and safe option for hemorrhagic CRP patients with giant ulcers.

Gegen Qinlian decoction enhances immunity and protects intestinal barrier function in colorectal cancer patients via gut microbiota

BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD)-1 inhibitors to treat microsatellite stable(MSS)tumor-bearing mice.However,the effect of GQD on patients with colorectal cancer(CRC)is not clear.AIM To determine the therapeutic mechanism of GQD in improving immune function,reducing inflammation and protecting intestinal barrier function.METHODS Seventy patients with CRC were included in this study:37 in the control group and 33 in the treatment group.The proportions of CD4+T,CD8+T,natural killer(NK),NKT and T regulatory cells were measured by flow cytometry.Levels of the cytokines tumor necrosis factor(TNF)-α,interferon(IFN)-γ,interleukin(IL)-2,IL-6,IL-10 and serotonin(5-hydroxytryptamine;5-HT)in serum were assessed by enzyme-linked immunosorbent assay(ELISA).The expression of zonula occludens(ZO)-1,occludin,nuclear factor(NF)-κB and TNF-αin tumor and normal tissues was measured by immunohistochemistry.The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis.RESULTS There were no adverse events in the treatment group.The proportion of CD4+T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups(P<0.05).The level of TNF-αin the posttreatment group was significantly lower than that in the pre-treatment and control groups(P<0.05).The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group(P<0.05).The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group(P<0.05).The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group(P=0.010).Compared with the control group,expression of NF-κB and TNF-αin tumor tissues of the treatment group was significantly decreased(P<0.05).Compared with the pre-treatment group,GQD decreased the relative abundance of Megamonas and Veillonella.In addition,GQD increased the relative abundance of Bacteroides,Akkermansia and Prevotella.CONCLUSION GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.

LC-ESI-MS/MS,a modified method for simultaneous quantification of isoflavonoids,flavonoids,alkaloids and saponins in a Chinese herbal preparation Gegen-Qinlian decoction

A sensitive and reliable liquid chromatography-electrospray ionisation-tandem mass spectrometry(LC-ESI-MS/MS)method was established to simultaneously quantitate four categories of compounds(isoflavonoids,flavonoids,alkaloids and saponins)in Gegen-Qinlian decoction(GQD).These compounds were separated by a Shiseido CAPCELL PAK C18 column with a linear gradient consisting of 0.1%(v/v)formic acid in water(A)and 0.1%(v/v)formic acid in acetonitrile(B),and delivered at a flow rate of 0.3 mL/min.All the analytes were determined by electrospray positive ionization tandem mass spectrometry in a multiple reaction monitoring(MRM)mode.Linearity,accuracy,precision,recovery and stability of the method were evaluated with the validation over the range of 4.0-538 5 ng/mL.The proposed method was applied to the analysis of a Chinese herbal preparation GQD successfully.

Study on the molecular mechanism of Gegen Qinlian decoction in the treatment of influenza based on network pharmacology

Objective:The study shows that Gegen Qinlian decoction(GGQL)is feasible in the treatment of influenza.It is explained from traditional Chinese medicine theory and modern pharmacology,and the formula is tested in vitro.The results show that Gegen Qinlian decoction has a good inhibitory effect on influenza virus.Methods:Search TCMSP database to get the components and targets of GGQL,and construct the compound target network.Then search OMIM database and Disgenet database to obtain influenza genes,and the common genes were obtained by VennDiagram.STRING database was used to construct gene function association network.Finally,David database was used to analyze GO enrichment and pathway enrichment.Results:146 ingredients and 128 targets were obtained,588 genes were obtained.46 common genes were obtained by VennDiagram,and import the common genes into the STRING database and construct the gene function association network,then the network information data was imported into Cytoscape software for topology analysis.Finally,13 enriched GO clusters and 7 enriched pathway clusters were obtained by David database,and construct the targets-GO-pathway network.Conclusion:Network pharmacology of GGQL reveal that the target and the pathway of the drug was closely related to influenza,and the results of this study have been verified with published experimental studies,which shows that GGQL has not only theoretical basis for the treatment of influenza,but also in vitro experiments support this conclusion.

Explanation of Gegen Qinlian Decoction Syndrome and Its Clinical Application

Gegen Qinlian Decoction is one of the commonly used classical prescriptions,which consists of fourherbs:Gegen(Puerariae Lobatae Radix),Huangqin(Scutellariae Radix),Huanglian(Coptidis Rhizoma),and Zhigancao Glycyrrhizae Radix et Rhizoma Praeparata cum Melle.The clinical application experience of Gegen Qinlian Decoction is as follows:first,according to Zhongjing Zhang's original text,heat distressing the large intestine with unresolved exterior syndrome is theoriginal meaningof Gegen Qinlian Decoction syndrome.In clinical practice,bacillary dysentery,gastrointestinal cold,etc.,belong to simultaneous exterior and interior disease,which are completely consistent with the original meaning of this prescription;second,the clinical digestive system diseases with exuberant heat of the large intestine as the core manifestation cannot be treated merely based on the exterior syndrome;third,due to the interior-exterior relationship between the lung and the large intestine and between the meridians,the use of Gegen(Puerariae Lobatae Radix),Huangqin(Scutellariae Radix),and Huanglian(Coptidis Rhizoma)can make the source of body clear,and the waste qi can be released and thepore can be easily opened,so this prescription can also be used for exogenous fever;fourth,with multidimensional comprehensive understanding of the syndrome,pathogenesis,symptoms and pharmacology,Gegen Qinlian Decoction has also been further applied to the treatment of hypertension,diabetes,etc.

Double-blinded,randomized clinical trial of Gegen Qinlian decoction pinpoints Faecalibacterium as key gut bacteria in alleviating hyperglycemia

Background:Accumulating evidence suggests that metabolic disorders,including type 2 diabetes mellitus(T2DM),can be treated with traditional Chinese medicine formulas,such as the Gegen Qinlian decoction(GQD).This study elucidates the mechanisms by which gut microbes mediate the anti-diabetic effects of GQD.Methods:We conducted a double-blind randomized clinical trial involving 120 untreated participants with T2DM.During the 12-week intervention,anthropometric measurements and diabetic traits were recorded every 4 weeks.Fecal microbiota and serum metabolites were measured before and after the intervention using 16S rDNA sequencing,liquid chromatography-mass spectrometry,and Bio-Plex panels.Results:Anti-diabetic effects were observed in the GQD group in the human trial.Specifically,glycated hemoglobin,fasting plasma glucose,and two-hour postprandial blood glucose levels were significantly lower in the GQD group than in the placebo group.Additionally,Faecalibacterium was significantly enriched in the GQD group,and the short-chain fatty acid levels were higher and the serum inflammation-associated marker levels were lower in the GQD group compared to the placebo group.Moreover,Faecalibacterium abundance negatively correlated with the levels of serum hemoglobin,fasting plasma glucose,and pro-inflammatory cytokines.Finally,the diabetes-alleviating effect of Faecalibacterium was confirmed by oral administration of Faecalibacterium prausnitzi(DSMZ 17677)in T2DMmousemodel.Conclusions:GQD improved type 2 diabetes primarily by modulating the abundance of Faecalibacterium in the gut microbiota,alleviating metabolic disorders and the inflammatory state.

葛根芩连汤加味治疗急性肠炎的临床观察

目的探究葛根芩连汤加味治疗急性肠炎的效果。方法纳入急性肠炎患者共80例,按照随机数字表法分为对照组与观察组各40例。对照组接受奥美拉唑等常规西医治疗,观察组在此基础上加用葛根芩连汤治疗。观察两组疗效,并比较治疗前后中医证候积分、炎症指标[肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL6)、超敏C反应蛋白(hs-CRP)、降钙素原(PCT)]、白蛋白、前白蛋白及免疫指标[免疫球蛋白G(IgG)、免疫球蛋白A(IgA)、免疫球蛋白M(IgM)]。结果观察组临床总有效率为95.00%,比对照组的80.00%高(P<0.05)。两组治疗后胃脘疼痛、身热不扬、大便稀溏、恶心呕吐评分比治疗前低,且观察组比对照组低(P<0.05);TNF-α、IL-6、hs-CRP及PCT比治疗前低,且观察组比对照组低(P<0.05);白蛋白、前白蛋白、IgG、IgA及IgM比治疗前高,且观察组比对照组高(P<0.05)。结论中西医结合治疗急性肠炎疗效确切,可明显抑制患者炎症反应,改善其血清白蛋白、前白蛋白水平。

The potential role of Gegen Qinlian decoction in the treatment of coronavirus disease 2019 based on network pharmacology and validation of lipopolysaccharide-induced macrophages

Background:Coronavirus disease 2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2,which has led to deaths and currently lacks an efficient treatment.Despite studies suggesting the potential of the Gegen Qinlian decoction(GQD)in preventing COVID-19,comprehensive analyses of its anti-COVID-19 potential are still lacking.Methods:GQD treatment was evaluated for its efficacy in ameliorating the early stage(24 hours)of lipopolysaccharide(LPS)-induced cytokine storm in vivo.Additionally,target genes of GQD were co-analyzed with COVID-19 signature genes to identify key ingredients and their pathways.Validation was also conducted using an LPS-induced macrophage model.Results:GQD treatment effectively ameliorated the early stage of LPS-induced cytokine storm in vivo.Key ingredients such as quercetin were found to be involved in multiple pathways,including inflammation,immunity,oxidative stress,cell proliferation,and apoptosis,through the AGE-RAGE signaling pathway and IL-17 signaling pathway.In the LPS-induced macrophage model,quercetin inhibited macrophage polarization(M1)and the secretion of inflammatory factors(IL-6,TNF-α,IL-17A).Conclusions:Our results indicate that GQD can be utilized in the treatment of cytokine storm induced by COVID-19 and has the potential to treat COVID-19 by suppressing the COVID-19 signature genes and macrophage polarization.

葛根治疫浅析

葛根治疫,溯源弥久。性平辛甘,善走表以升阳解肌、通络以生津解毒,多用于诊治温热疫。如徐氏葛根汤,合膏、芩清解少阳阳明邪热,合麻黄透邪外达、截断病势,以治天行热疫之痘疹欲出者;陈氏葛根汤,合荆、桔、翘等轻清扬上之品,以治疫毒蕴结肺胃之疫痧证;《局方》升麻葛根汤,合升麻火郁发之,以治麻疹初起不透者;陈氏升麻葛根汤,合柴、芩、栀疏利清解三焦,以治气滞血热之丹毒证。现代药理,则多从免疫应答、炎症介质角度阐述其解热、抗病毒等治疫机制。通过上述对葛根药性、方剂配伍、药理研究多个角度的系统梳理,探讨其治疫理论及机制,为临床应用及新药开发提供参考依据。

桂枝加葛根汤联合当归芍药散治疗良性位置性眩晕的效果

目的 探讨桂枝加葛根汤联合当归芍药散治疗良性位置性眩晕(benign paroxysmal positional vertigo,BPPV)的效果。方法 选取2021年2月-2023年8月收治的80例老年后半规管BPPV痰瘀互阻证患者,按照掷硬币法分为2组,对照组(n=40)采取常规西药治疗,观察组(n=40)另用桂枝加葛根汤联合当归芍药散治疗,比较2组疗效。结果 治疗7 d、14 d后,观察组中医证候积分较对照组低(P<0.05)。14 d治疗后,观察组眩晕评分、血液流变学指标、血清同型半胱氨酸(homocysteine,Hcy)水平均优于对照组(P<0.05)。治疗后,观察组脑血流动力学较对照组优(P<0.05)。2组在治疗期间均未出现头痛、乏力不良反应。结论 对老年后半规管BPPV痰瘀互阻证患者采取桂枝加葛根汤联合当归芍药散治疗,可明显减轻患者眩晕症状和中医证候积分,改善其血液流变学和脑血流动力学,值得推广。

葛根黑苏汤联合神经肌肉电刺激、戊酸雌二醇治疗薄型子宫内膜不孕症临床研究

目的:观察葛根黑苏汤联合神经肌肉电刺激、戊酸雌二醇对薄型子宫内膜不孕症患者子宫内膜形态、血清白血病抑制因子(LIF)水平及妊娠成功率的影响。方法:选取150例薄型子宫内膜不孕症患者,按随机数字表法分为常规组、电刺激组、联合组各50例。常规组采用戊酸雌二醇口服治疗,电刺激组使用戊酸雌二醇联合神经肌肉电刺激进行治疗,联合组采用葛根黑苏汤、神经肌肉电刺激、戊酸雌二醇的方式进行治疗。比较3组治疗前后中医证候积分、子宫内膜形态、血清学指标值[血清白血病抑制因子(LIF)、白细胞介素-10(IL-10)]的变化,比较3组妊娠率。结果:治疗后,3组形寒肢冷、性欲低下、眩晕耳鸣中医证候积分均较治疗前下降,联合组上述3项中医证候积分均低于常规组、电刺激组(P<0.05)。治疗后,得到A型子宫内膜形态在常规组、电刺激组、联合组中分别占24.00%、48.00%、54.00%。联合组子宫内膜厚度高于常规组、电刺激组,子宫内膜形态及厚度与常规组、电刺激组比较,差异均有统计学意义(P<0.05)。治疗后,3组血清LIF、IL-10水平均较治疗前升高(P<0.05),联合组血清LIF、IL-10水平均高于常规组、电刺激组(P<0.05)。常规组妊娠成功率为16.00%,电刺激组妊娠成功率28.00%,联合组妊娠成功率38.00%,联合组妊娠成功率高于常规组、电刺激组(P<0.05)。结论:葛根黑苏汤联合神经肌肉电刺激、戊酸雌二醇可有效改善薄型子宫内膜不孕症患者的子宫内膜形态及血清LIF水平,提高妊娠率。

葛根芩连汤加减联合二甲双胍对2型糖尿病胃肠湿热证患者中医证候积分及胰岛功能的影响

目的探讨葛根芩连汤加减联合二甲双胍对2型糖尿病(type 2 diabetes mellitus,T2DM)胃肠湿热证患者的影响。方法选取2022年4月—2023年12月深圳市中医院收治的78例T2DM胃肠湿热证患者为研究对象,根据不同治疗方法分为对照组和观察组,各39例。对照组口服盐酸二甲双胍片,观察组在对照组基础上给予葛根芩连汤加减治疗。对比两组的中医证候积分、血糖水平(空腹血糖、餐后2 h血糖、糖化血红蛋白)、胰岛功能(胰岛素抵抗指数、胰岛β细胞功能指数)、不良反应。结果治疗后,观察组的中医证候积分低于对照组,差异有统计学意义(P<0.05)。观察组空腹血糖、餐后2 h血糖、糖化血红蛋白水平均低于对照组,差异有统计学意义(P均<0.05)。治疗后,两组胰岛素抵抗指数水平均降低,且观察组低于对照组,两组胰岛β细胞功能指数均提高,且观察组高于对照组,差异有统计学意义(P均<0.05)。结论在T2DM胃肠湿热证患者中使用葛根芩连汤加减与二甲双胍联合治疗,可有效改善中医证候、血糖水平及胰岛功能,安全性高。

葛根芩连汤加减联合美沙拉嗪治疗大肠湿热型溃疡性结肠炎临床效果及其对肠道菌群、免疫功能和炎症水平的调节

目的观察葛根芩连汤加减联合美沙拉嗪治疗大肠湿热型溃疡性结肠炎的临床效果及其对患者肠道菌群、免疫功能和炎症水平的调节作用。方法选择2020年1月—2022年12月在医院消化内科治疗的100例溃疡性结肠炎患者作为研究对象,按照随机数字表法将患者平均分为美沙拉嗪组和葛根芩连组,各组50例,美沙拉嗪组患者单纯口服美沙拉嗪治疗,葛根芩连组患者在美沙拉嗪组基础上联合葛根芩连汤加减治疗。观察两组患者的临床效果和不良反应情况,并比较干预前后血清炎症因子、免疫功能以及肠道菌群变化。结果美沙拉嗪组患者的有效率为80.00%(40/50),葛根芩连组患者的有效率为94.00%(47/50),与美沙拉嗪组比较,葛根芩连组的有效率明显升高(P<0.05)。干预4周后,与美沙拉嗪组比较,葛根芩连组患者的血清白介素(IL)-6、IL-8、γ-干扰素(IFN-γ)以及肿瘤坏死因子-α(TNF-α)水平均明显下降(P<0.01);葛根芩连组患者外周血中CD_(3)^(+)、CD_(4)^(+)以及CD_(4)^(+)/CD_(8)^(+)水平明显升高,而CD_(8)^(+)水平则明显下降(P<0.01)。且葛根芩连组患者肠道双歧杆菌、乳酸杆菌以及肠球菌水平相较于美沙拉嗪组均明显升高,差异具有统计学意义(P<0.01)。干预4周后,葛根芩连组患者的IBDQ评分和SF-36评分相较于美沙拉嗪组均明显升高,差异具有统计学意义(P<0.01)。治疗期间两组患者的主要不良反应有腹胀、消化不良、头晕头痛、乏力、皮疹等,美沙拉嗪组和葛根芩连组的不良反应总发生率分别为10.00%(5/50)、14.00%(7/50),差异无统计学意义(P>0.05)。结论葛根芩连汤加减联合美沙拉嗪能够提高大肠湿热型溃疡性结肠炎患者的临床疗效,抑制血清炎症水平,调节机体免疫功能,其作用机制与调节患者肠道菌群平衡有关。

补肾活血法与葛根黑苏汤对薄型子宫内膜不孕症治疗作用的影响

目的探究补肾活血法与葛根黑苏汤对薄型子宫内膜不孕症患者中医证候积分及炎症的影响。方法选取2020年3月—2022年3月在该院妇科就诊的80例薄型子宫内膜不孕症患者,按随机数字表法将分为对照组和观察组,各40例。对照组采用葛根黑苏汤治疗,观察组采用葛根黑苏汤联合补肾活血法治疗。对比两组患者中医证候积分、子宫内膜厚度、血清血管内皮生长因子(vascubr endothelial growth factor,VEGF)、子宫血流动力学、血清雌二醇及孕酮、子宫内膜类型、血清炎症因子水平。结果治疗后,两组中医证候积分均下降,且对照组明显低于观察组(P<0.05)。治疗前两组子宫内膜厚度以及血清VEGF水平比较,差异无统计学意义(P>0.05),治疗后,两组子宫内膜厚度以及血清VEGF水平均升高(P<0.05),且观察组低于对照组。治疗前两组子宫血流动力学指标水平比较,差异无统计学意义(P>0.05);治疗后,两组搏动指数、阻力指数均降低,收缩期血流速度加快,差异无统计学意义(P<0.05);观察组收缩期血流速度快于对照组,搏动指数、阻力指数低于对照组。治疗前两组血清雌二醇与孕酮水平比较,差异无统计学意义(P>0.05);两组患者血浆中的雌二醇和黄体素含量均升高,而对照组则显著增高(P<0.05)。治疗前两组子宫内膜A+B型与C型数量比较,差异无统计学意义(P>0.05);治疗后对照组A+B型数量高于对照组,C型数量低于对照组(P<0.05)。治疗前两组血清因子水平比较,差异无统计学意义(P>0.05)。治疗后两组血清因子水平均下降,且对照组低于观察组(P<0.05)。结论采用补肾活血法联合葛根黑苏汤治疗薄型子宫内膜不孕症能减轻患者的中医证候,改善患者子宫内膜形态、厚度,调节患者血清VEGF水平、血流动力学、血清雌二醇及孕酮水平,降低血清炎症因子,值得在临床上进一步推广使用。

葛根芩连汤治疗溃疡性结肠炎研究进展

溃疡性结肠炎(ulcerative colitis,UC)是一种慢性复发性的结肠和直肠的炎症性疾病,其典型表现为腹痛、腹泻、黏液脓血便和吸收障碍等,属中医“肠澼”“痢疾”“滞下”“泄泻”“脏毒”等范畴。葛根芩连汤出自《伤寒论》,善清胃肠湿热,亦可调和气血,原方由葛根、黄芩、黄连和炙甘草4味中药组成,是治疗UC的经典良方。临床应用方面,主要通过葛根芩连汤加减、联合其他方剂、联合西药、联合灌肠、联合针灸等方式治疗UC患者,其优势体现在改善肠道黏膜屏障功能损伤,减少肠道炎症反应,缓解腹泻、腹痛、脓血便、里急后重、肛门灼热等症状,降低复发率,减少不良反应等,有效提高了UC患者的生活质量。作用机制方面,葛根芩连汤治疗UC主要与调节自身免疫、降低炎性细胞因子、调节T细胞、抗氧化应激、改善肠道菌群失调,调节IL-6/JAK2/STAT3、TLR4/NF-κB、Notch、Nrf2等信号通路有关。葛根芩连汤中单味药有效成分的研究表明,黄芩苷、黄芩多糖、葛根素、小檗碱、甘草酸二铵、甘草次酸等是治疗UC的主要有效成分。文章检索近年来国内外文献,从临床应用研究和实验机制研究两个方面综述葛根芩连汤治疗UC的研究进展,以期为葛根芩连汤治疗UC的遣方用药及后续研究葛根芩连汤治疗UC的作用机制提供参考依据,发挥中医药治疗UC的优势。

基于miR21/PI3K-Akt/SREBP通路研究泽泻汤对高脂血症模型小鼠的调脂作用机制

目的 探索经典名方泽泻汤对高脂血症模型小鼠的调脂作用机制。方法 采用ELISA法检测血清中血脂四项、肝功能指标及胆固醇脂酰转移酶(LCAT)水平。采用HE和油红O染色法判断肝组织病理情况。采用网络药理学预测泽泻汤降脂相关靶点,实现对交集靶点GO功能和KEGG通路富集分析。采用PCR芯片技术检测网络药理学筛选的目的基因,应用qPCR和Western blot检测基因和蛋白表达量。结果 泽泻汤可显著调节高脂血症模型小鼠的血脂四项水平,改善因高脂引起的肝损伤指标升高,对肝脏组织中脂质代谢关键酶HMGR、CYP7A1及脂质转运体ABCA1、Apo-A1具有反向调节作用。HE和油红O染色显示,泽泻汤可改善肝组织病理形态,减轻肝组织的脂质沉积情况,阳性面积比率显著下降(P<0.01)。PCR芯片获取反向调节基因44个,GO功能富集分析获取了266个条目,KEGG通路富集分析筛选得到99条信号通路。qPCR及Western blot结果显示,泽泻汤组显著下调PIK3CG、AKT1、IL-6基因表达量(P<0.05,P<0.01),上调ABCG1基因表达量(P<0.05),下调PI3 Kinase p110β、p-AKT(Ser473)及SREBP-1c蛋白表达水平(P<0.01);泽泻汤能够反向调节miR21-5p(P<0.01)。结论 泽泻汤对高脂血症模型小鼠脂代谢具有显著的调节作用,能改善高脂血症引起的肝损伤,其调脂作用可能与调节胆固醇在体内代谢、转运有关,与miR21/PI3K-Akt/SREBP通路密切相关,且泽泻汤全方调脂效果优于单味药。

葛根芩连汤对2型糖尿病db/db小鼠胰腺组织PERK/ATF4/CHOP信号通路的影响

目的观察葛根芩连汤对2型糖尿病(T2DM)小鼠胰腺内质网应激的影响,探讨其治疗T2DM的作用机制。方法75只SPF级雄性db/db小鼠随机分为模型组、二甲双胍组和葛根芩连汤高、中、低剂量组,每组15只,15只db/m小鼠作为空白组,给药组分别予相应药物灌胃12周。检测小鼠体质量、空腹血糖(FBG)及糖化血红蛋白(HbA1c),HE染色观察胰腺组织病理变化,TUNEL染色检测胰岛细胞凋亡情况,Western blot检测胰腺组织葡萄糖调节蛋白78(GRP78)、蛋白激酶R样内质网激酶(PERK)、p-PERK、活化转录因子4(ATF4)、C/EBP同源蛋白(CHOP)蛋白表达,实时荧光定量PCR检测胰腺组织PERK、ATF4、CHOP mRNA表达。结果与空白组比较,模型组小鼠体质量、FBG和HbA1c含量显著增加(P<0.01);胰腺组织结构不完整,边界模糊,内有空泡,胰岛细胞凋亡明显增加(P<0.01);胰腺组织GRP78、p-PERK、ATF4、CHOP蛋白表达显著升高(P<0.01),PERK、ATF4、CHOP mRNA表达显著升高(P<0.01)。与模型组比较,各给药组小鼠体质量、FBG和HbA1c含量显著减少(P<0.05,P<0.01);胰腺组织病理改变有所减轻,胰岛细胞凋亡不同程度减少(P<0.05,P<0.01);葛根芩连汤高、中剂量组和二甲双胍组胰腺组织GRP78、p-PERK、ATF4、CHOP蛋白表达显著降低(P<0.01),PERK、ATF4、CHOP mRNA表达显著降低(P<0.05,P<0.01)。结论葛根芩连汤可能通过抑制内质网应激PERK/ATF4/CHOP信号通路,下调相关基因和蛋白表达,减少胰岛细胞凋亡,保护胰岛细胞功能,延缓T2DM进展。

葛根芩连汤对胰岛素抵抗大鼠肝脏能量代谢及游离脂肪酸的影响

目的探讨葛根芩连汤对胰岛素抵抗(IR)大鼠肝脏能量代谢及游离脂肪酸(FFA)的影响。方法采用60%脂肪的高脂饲料连续喂养13周复制IR大鼠模型。将SD大鼠随机分为正常组、模型组、罗格列酮组(5 mg·kg^(-1))以及葛根芩连汤低、中、高剂量组(1.65、4.96、14.86 g·kg^(-1)),每组6只。灌胃给药,每天1次,连续给药干预16周。测定IR相关指标:血清空腹胰岛素(FINS)、空腹血糖(FPG)值,计算IR指数;建立HPLC法测定大鼠肝组织中三磷酸腺苷(ATP)、二磷酸腺苷(ADP)、一磷酸腺苷(AMP)含量;采用ELISA法测定大鼠肝组织中的FFA含量;采用全自动生化分析仪检测血清总胆固醇(TC)、甘油三酯(TG)含量;采用HE染色法观察肝脏组织病理变化。结果(1)模型复制结束后,与正常组比较,模型组大鼠的FINS、FPG水平及IR指数显著升高(P<0.01);肝脏组织中ATP、ADP、AMP、FFA含量均无明显变化(P>0.05)。(2)给药干预结束后,与正常组比较,模型组大鼠的FINS、FPG水平及IR指数显著升高(P<0.01),肝脏组织中ATP、ADP、AMP含量均显著下降(P<0.01),FFA含量显著升高(P<0.01),血清TC、TG水平均明显升高(P<0.05);肝细胞排列紊乱,出现脂肪变性,并存在大量脂滴。与模型组比较,各给药组大鼠的FINS水平及IR指数均明显降低(P<0.05,P<0.01),罗格列酮组大鼠的FPG水平明显降低(P<0.05);各给药组大鼠肝脏组织中ADP、AMP含量均明显升高(P<0.05、P<0.01),葛根芩连汤低、中、高剂量组大鼠肝脏组织中ATP含量明显升高(P<0.05、P<0.01);罗格列酮组及葛根芩连汤低、高剂量组大鼠肝脏组织中FFA含量均显著降低(P<0.01);葛根芩连汤低、高剂量组大鼠血清TC水平明显降低(P<0.05,P<0.01),罗格列酮组及葛根芩连汤低剂量组大鼠血清TG水平明显降低(P<0.05,P<0.01);各给药组大鼠的肝细胞脂肪变性有不同程度减轻,且脂滴减少,病理损伤得到改善。结论葛根芩连汤可能通过调节能量代谢并降低FFA水平,从而改善肝脏脂质代谢紊乱,恢复脂质与能量平衡,从而起到改善IR的作用。

葛根汤联合中药热敷治疗神经根型颈椎病风寒阻络证临床观察

目的 观察葛根汤联合中药热敷治疗神经根型颈椎病风寒阻络证的临床效果。方法 选取吉林省吉林中西医结合医院骨伤科2021年7月—2022年7月收治的90例神经根型颈椎病风寒阻络证患者,运用掷硬币法分为2组,各45例。对照组用葛根汤治疗,观察组使用葛根汤加中药热敷治疗,比较2组颈椎功能障碍评分、临床疗效、颈肩疼痛程度评分。结果 治疗后,对照组总有效率低于观察组(P<0.05);观察组的颈椎功能障碍评分与颈肩疼痛程度评分更低(P<0.05)。结论 葛根汤联合中药热敷治疗神经根型颈椎病风寒阻络证临床效果较好,优于单一使用葛根汤治疗的方式,有较高临床应用价值。