Therapeutic effect of Wendan Decoction combined with mosapride on gastroesophageal reflux disease after esophageal cancer surgery

BACKGROUND Gastroesophageal reflux disease(GERD)is a common complication of esophageal cancer surgery that can affect quality of life and increase the risk of esophageal stricture and anastomotic leakage.Wendan Decoction(WDD)is a traditional Chinese herbal formula used to treat various gastrointestinal disorders,such as gastritis,functional dyspepsia,and irritable bowel syndrome.Mosapride,a prokinetic agent,functions as a selective 5-hydroxytryptamine 4 agonist,enhancing gastrointestinal motility.AIM To evaluate the therapeutic effects of WDD combined with mosapride on GERD after esophageal cancer surgery.METHODS Eighty patients with GERD were randomly divided into treatment(receiving WDD combined with mosapride)and control(receiving mosapride alone)groups.The treatment was conducted from January 2021 to January 2023.The primary outcome was improved GERD symptoms as measured using the reflux disease questionnaire(RDQ).The secondary outcomes were improved esophageal motility(measured using esophageal manometry),gastric emptying(measured using gastric scintigraphy),and quality of life[measured via the Short Form-36(SF-36)Health Survey].RESULTS The treatment group showed a notably reduced RDQ score and improved esophageal motility parameters,such as lower esophageal sphincter pressure,peristaltic amplitude,and peristaltic velocity compared to the control group.The treatment group showed significantly higher gastric emptying rates and SF-36 scores(in both physical and mental domains)compared to the control group.No serious adverse effects were observed in either group.CONCLUSION WDD combined with mosapride is an effective and safe therapy for GERD after esophageal cancer surgery.It can improve GERD symptoms,esophageal motility,gastric emptying,and the quality of life of patients.Further studies with larger sample sizes and longer follow-up periods are required to confirm these findings.

Mechanism of Wendan decoction in preventing obesity by regulating multiple signal pathway networks based on gene promoter methylation

Objective:To investigate the potential mechanism of Wendan decoction in obesity by screening target genes with promoter region methylation changes and constructing a multiple signaling pathways network based on promoter methylation.Methods:The methylation degree of Itgad,Col8a1,Adra2b,Jund,Rab2a,Wnt8b,Fzd9,B4galt7,Pik3cd,Creb1,Stard8,and Mmp1 in the abdominal adipose tissue of obese rats was determined using the Agena MassARRAY system.Western blot was performed to assess protein expression levels.Target genes were identified based on the methylation degree in the promoter region and protein expression.Enrichment analysis of signaling pathways was conducted to identify relevant target genes and obtain a multiple signaling pathway network associated with obesity.Core and terminal effector molecules in the pathway networks were selected as research targets for reverse transcription-polymerase chain reaction(RT-PCR)analysis.Results:Four genes(Adra2b,Creb1,Itgad,and Pik3cd)showed a degree of promoter methylation consistent with their respective protein expression levels.Among them,Adra2b,Creb1,and Pik3cd expression increased,while that of Itgad decreased.Enrichment analysis revealed that Creb1 and Pik3cd were involved in 6 signaling pathways related to obesity:tumor necrosis factor(TNF)signaling pathway,growth hormone synthesis/secretion and action,adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,relaxin signaling pathway,cyclic nucleotide(cAMP)signaling pathway,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Subsequently,a multiple signaling pathways network was constructed based on promoter methylation.Key molecules including protein kinase B(AKT),mechanistic target of rapamycin complex 1(mTORC1),and unc-51 like autophagy activating kinase 1(ULK1),as well as terminal effector molecules interleukin-1β(IL-1β),interleukin-6(IL-6),and chemokine(C-X-C motif)ligand 2(CXCL2)were selected as research targets.Wendan decoction decreased the expressions of AKT,mTORC1,IL-1β,IL-6,and CXCL2 while up-regulating ULK1 expression.Conclusion:The mechanism of Wendan decoction in preventing obesity involves the regulation of multiple signaling pathways through the control of Creb1 and Pik3cd gene promoter methylation.However,the associated multi-path gene regulation mechanism in preventing obesity is complex.Thus,further exploration is needed to elucidate the role of methylation changes in this mechanism.

Initial steps on the analysis of the underlying pharmacological mechanisms of Wendan decoction on sudden deafness using network pharmacology and molecular docking

Background:Despite its widespread therapeutic use and effectiveness,the underlying pharmacologic mechanisms of Wendan decoction(WDD)and how it works to treat sudden deafness(SD)remain unclear.In this study,the pharmacological mechanisms of WDD underlying SD were analyzed using network pharmacology and molecular docking.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was employed to identify the active compounds and target genes of WDD,and genes associated with SD were screened on five databases.RGUI conducted Gene Ontology(GO)functional and the Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.A compound-target network was established using Cytoscape,and the STRING database created a protein-protein interaction(PPI)network to identify the key compounds and targets.Subsequently,a network of crucial compound-target was generated for further molecular docking analysis.For molecular docking simulations of the macromolecular target proteins and their matching ligand molecules,AutoDock Vina and AutoDockTool were utilized.Results:TCMSP identified 162 active target genes and 36 active compounds for WDD.The active target genes were compared with the 2271 genes associated with SD to identify 70 intersecting active target genes linked to 34 active compounds.The GO functional enrichment and KEGG pathway enrichment analyses were undertaken,and compound–target,and PPI networks were built.The key compounds and protein targets were identified and integrated to form a key compound–target network.Eventually,molecular docking was performed to investigate the interactions of the protein targets with their respective compounds.Conclusion:This study highlights the mechanisms of multi-compounds,targets,and pathways of WDD acting on SD and provides further evidence of crucial compounds and their matching target proteins of WDD acting on SD.

Bibliometric analysis of Wendan decoction research based on the Web of Science database

Objective:With the development of Wendan decoction(WDD)and more literature on the research of WDD,we aimed to present an insight into WDD research using bibliometric analysis.Methods:We retrieved data from the Web of Science database from 2008 to 2022.Publication trends were examined using data from journals,authors,institutions,international collaborations,citations,and keywords from the online analytical platform Bibliometric(http://bibliometric.com).Results:Over the years,an increase in the use of keywords,including depression,insomnia,Alzheimer’s disease,schizophrenia,hippocampus,and insomnia,was observed.The outcomes of the analysis revealed that topics related to WDD have become increasingly prevalent in the last five years,and the internationally recognized application of WDD is mainly neuropsychiatric diseases.Conclusion:We exhibited WDD research progress by identifying and evaluating WDD-focused articles.Our analysis revealed the trend of the topics from 2008 to 2022,which can assist scholars in identifying future trends.

The Mechanism of Regulating Leptin Resistance in Obesity and the Influence of Adjusting Methylation of OB-R,POMC Gene Promoter of Wendan Decoction (温胆汤)

Objective:To explore the mechanism of Wendan Decoction(温胆汤)regulating leptin resistance in obesity by analyzing the level of leptin in peripheral blood,the expression of leptin receptor and signal pathway molecule POMC in hypothalamus.To analyze the methylation status of the gene promoters of leptin receptor and POMC in obese rats fed with high fat diet,and the influence of adjusting methylation of OB-R,POMC gene promoter about Wendan decoction.Methods:Model rats were randomly divided into model control group and drug observation group,additional normal rats with 8 rats in each group.The models were established by high fat diet.The observation group was treated with Wendan Decoction(温胆汤)and the other two groups were treated with sterilized drinking water once a day for 6 weeks.Body weight was recorded every week during the intervention.Peripheral blood and hypothalamus were collected at the end of the experiment.The serum leptin level was measured by ELISA method,and the expression of OB-R and POMC in hypothalamus was detected by RT-qPCR method.Methylation level of OB-R and POMC promoter detected by methylation specific PCR.Results:Our results revealed that Wendan Decoction(温胆汤)could effectively reduce body weight,the body weight in the drug observation group was significantly lower than that in the model control group,and the difference between the two groups was statistically significant.The level of leptin in peripheral blood and the expression of OB-R in hypothalamus were consistent with the trend of body weight.The heavier the weight,the higher the level of leptin and OB-R.Wendan Decoction(温胆汤)could reduce the level of leptin and OB-R in peripheral blood while reducing body weight.Compared with the model control group,the difference was statistically significant.The heavier the weight,the lower the level of POMC expression.Wendan Decoction(温胆汤)could increase the expression of POMC while reducing body weight,which had statistical significance compared with the model control group.The methylation status of OB-R and POMC promoter in hypothalamus was not significantly associated with obesity induced by high fat diet,and Wendan Decoction(温胆汤)had no effect on methylation status.Conclusions:Wendan Decoction(温胆汤)could inhibit obesity by affecting the expression of leptin receptor and POMC mRNA in hypothalamus to a large degree.There was no obvious change about the methylation status of the gene promoters of leptin receptor and POMC in obese rats fed with high fat diet.And it was not related to the change of methylation status of gene promoter about the mechanism of Wendan Decoction(温胆汤).

Effect of the modified wendan decoction on hippocampal astrocyte neurotrophy by regulating the TRP-KYN metabolic pathway in depression-model rats

Objective:To observe the effect of the modified Wendan decoction on the neurotrophic function of hippocampal astrocytes by regulating the tryptophan-kynurenine(TRP-KYN)neuroprotective metabolic pathway in depression-model rats.Methods:A total of 96 Sprague Dawley(SD)rats were randomly divided into the blank group,model group,sham surgery group,neurotoxicity blocker group(blocker 1 for short)group,decoction group,fluoxetine group,blocker 1 plus decoction group,and blocker 1 plus fluoxetine group.Depression in rats of all groups,except for the blank group,was generated by isolation combined with chronic unpredictable mild stress.After corresponding treatments of the rats in each group,the sucrose preference test was performed to evaluate the depressive behaviors of the rats.Serum levels of tryptophan(TRP),kynurenine(KYN),and kynurenic acid(KYNA)were detected via enzyme-linked immunosorbent assay(ELISA);the mRNA/protein expression of hippocampal astrocyte markers,glial fibrillary acidic protein(GFAP)and S100β,was detected via reverse transcription-polymerase chain reaction(RT-PCR)and immunohistochemistry.ELISA and RT-PCR were carried out to detect the levels/mRNA expressions of brain-derived neurotrophic factor(BDNF)and glial-cell-line-derived neurotrophic factor(GDNF),the nutrient secretions of hippocampal astrocytes in rats.Results:Compared to the blank group,the number of activities of rats was significantly reduced,and the GFAP expression in the hippocampus was significantly increased while the BDNF and GDNF expressions were significantly decreased in the model group.With the intervention of the modified Wendan decoction,the depression of rats was significantly improved,and the BDNF and GDNF expressions in the hippocampus were increased while the GFAP expression was decreased significantly in the model group.Conclusion:The modified Wendan decoction may improve the neurotrophic function of rats’hippocampal astrocytes by enhancing the neuroprotective function of the TRP-KYN pathway,thereby exerting an antidepressant effect.

On the Modern Clinical Application of Wendan Decoction

Wendan Decoction is one of the commonly used prescriptions in clinical practice.it has a wide range of applications.On the basis of traditional Chinese medicine(TCM)syndrome differentiation,as long as it can be added or subdivided flexibly,it can be used to conquer various difficult and miscellaneous diseases seen in daily life.

A meta-analysis of Wendan decoction in the treatment of diabetic gastroparesis

目的系统评价温胆汤治疗糖尿病性胃轻瘫的临床疗效和安全性。方法检索PubMed、MEDLINE、TheCochrane Library、Embase、CBM、CNKI、VIP 及万方等数据库,纳入符合条件的临床随机对照试验。按照Cochrane 系统评价标准对纳入文献进行质量评价,应用RevMan 5.3 软件进行Meta 分析。结果共纳入7 个研究,533 例患者。Meta 分析结果显示,温胆汤治疗糖尿病胃轻瘫的有效率优于对照组[RR=1.30,95%CI(1.20~1.40), P<0.000 01]、对空腹血糖[MD=-0.43, 95% CI (-0.91,-0.01), P=0.05]的改善均优于西药。中药治疗组复发率[RR=0.29, 95% CI ( 0.13, 0.62), P=0.002]少于西药组。结论与西药相比,温胆汤对糖尿病胃轻瘫有较好疗效,同时能够降低其复发率。但由于纳入的文献实验质量较低且存在偏倚的可能,仍需大规模、高质量的临床随机对照试验进一步证实。

Effects of Jiawei Wendan decoction on hippocampal p-CREB protein expression in a rat model of depression

BACKGROUND： Jiawei W＇endan decoction can elevate hippocampal brain-derived neurotrophic factor （BDNF） protein expression in rats with depression. It has been hypothesized that Jiawei Wendan decoction can exhibit antidepressant effects through the hippocampal signal transduction pathway of cyclic adenosine monophosphate response element binding protein （CREB）-BDNF. OBJECTIVE： Using phosphorylated-CREB （p-CREB） as an entry point, the present study was designed to observe intervention effects ofJiawei Wendan decoction compared with fluoxetine. DESIGN, TIME AND SETTING： A randomized, controlled, cellular biology experiment was performed at the Central Laboratory of Guangxi University of Traditional Chinese Medicine, MATERIALS： A total of 40 healthy, male, Sprague-Dawley rats were included in the present study. Rhizoma Acori Talarinowii （Shichangpu）, Flos Albiziae （Hehuanhua）, Rhizoma Pinelliae （Banxia）, Caulis Bambusae in Taeniam （Zhuru）, Fructus Aurantii Immaturus （Zhishi）, Poria （Fuling）, and Radix Bupleuri （Chaihu）, the primary ingredients ofJiawei Wendan decoction, were purchased from First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine. The raw drug was decocted at a concentration of 1.5 g/mL. Fluoxetine capsules were purchased from Shanghai Zhongxi Pharmaceutical Co., Ltd., China. METHODS： Following behavioral testing, 36 rats were selected from the initial 40 rats according to similar behavioral scores, and were randomly divided into 4 groups： model （n = 8）, Jiawei Wendan decoction-treated （n = I 0）, fluoxetine-treated （~ = 10）, and normal control （n = 8）. All rats, except for those in the normal control group, were separately raised in a chronic and unpredictable, mild-stimulation environment for 2 l days to establish a depression model. The Jiawei Wendan decoction-treated and fluoxetine-treated groups were intragastrically administered Jiawei Wendan decoction （12 g/kg/d） and fluoxetine （1.8 mg/kg/d）, respectively. The model and normal control groups received double-distilled water （2 mL/kg/d） once a day for a total of 21 days. MAIN OUTCOME MEASURES： Prior to depression induction and subsequent to administration, memory and degree of depression were measured by open field and tail suspension tests, respectively. At 24 hours after administration, p-CREB expression in the hippocampat CA3 region was analyzed by the immunohistochemical SABC method. RESULTS： Two rats from the Jiawei Wendan decoction-treated group, and one from the fluoxetine-treated group, died of unknown causes. The remaining rats in each group, except for one rat that was randomly selected from the fluoxetine-treated group, were included in the final analysis. Following administration, the model group exhibited significantly decreased numbers of hippocampal p-CREB-positive cells, horizontal and vertical movements, and significantly prolonged duration of immobility in tail-suspension test, compared with the normal control group （P 〈 0.01）. The numbers of p-CREB-positive cells, as well as horizontal and vertical movements, were significantly greater, and the duration of immobility was significantly shorter, in the Jiawei Wendan decoction and fluoxetine groups, compared with the model group （P 〈 0.05-0.01）. There was no significant difference in the above-mentioned three indices between the Jiawei Wendan decoction and fluoxetine groups （P 〉 0.05）. CONCLUSION： Jiawei Wendan decoction increased hippocampal p-CREB expression by influencing the rat hippocampal signal transduction pathway of CREB-BDNF. Jiawei Wendan decoction exhibited antidepressant effects equivalent to fluoxetine.

Wendan decoction improves learning and memory deficits in a rat model of schizophrenia

An experimental model of schizophrenia was established using dizocilpine （MK-801）. Rats were intragastrically administered with Wendan decoction or clozapine for 21 days prior to establishing the model. The results revealed that the latency of schizophrenia model rats to escape from the hidden platform in the Morris water maze was significantly shortened after administration of Wendan decoction or clozapine. In addition, the treated rats crossed the platform significantly more times than the untreated model rats. Moreover, the rate of successful long-term potentiation induction in the Wendan decoction group and clozapine group were also obviously increased compared with the model group, and the population spike peak latency was significantly shortened. These experimental findings suggest that Wendan decoction can improve the learning and memory ability of schizophrenic rats to the same extent as clozapine treatment.

Efficacy of Wendan Decoction series for coronary heart disease with anxiety and depression:A systematic review and meta-analysis

Objective:To systematically evaluate the clinical efficacy of Wendan Decoction series combined with conventional western medicine in the treatment of coronary heart disease complicated with anxiety and depression.Methods:We searched four Chinese databases including CNKI,WanFang,VIP,SinoMed,and five English databases of PubMed,Cochrane Library,Web of Science,EMBASE,Springer Link for clinical randomized controlled trials of using Wendan Decoction series in the treatment of coronary heart disease complicated with anxiety and depression.Time range for searching was from the establishment of these databases to January 2022.Then we screened the retrieved literature according to the inclusion and exclusion criteria,and conducted data extraction and quality evaluation of the selected literature.Meta analysis was conducted using RevMan 5.3 software.Results:A total of 13 RCT studies and 1007 patients with coronary heart disease complicated with anxiety and depression were included.Meta-analysis showed that Wendan Decoction series combined with conventional western medicine treatment showed better effects in the improvement rate of clinical anxiety[RR=1.21,95%CI=(1.12,1.31),P<0.00001],the improvement rate of depression[RR=1.30,95%CI=(1.10,1.53),P=0.002],the improvement rate of angina pectoris[RR=1.28,95%CI=(1.13,1.44),P<0.0001],increasing the ECG improvement rate[RR=1.29,95%CI=(1.07,1.55),P=0.008],increasing the rate of reducing nitroglycerin usage[RR=1.68,95%CI=(1.25,2.25,P=0.0006],as well as increasing the improvement rate of TCM symptoms[RR=1.15,95%CI=(1.04,1.26),P=0.004].It also showed better effects in reducing clinical anxiety and depression scores(SAS,SDS,HAMA,HAMD),SAQ scores and TCM symptom scores.The differences were statistically significant.Conclusion:Wendan Decoction series combined with conventional western medicine shows advantages in treating coronary heart disease patients complicated with anxiety and depression in reducing the angina pectoris score,anxiety and depression score,as well as improving the clinical TCM symptoms.

Proteomics analysis of Huanglian Wendan decoction drug-containing serum on insulin resistance in 3T3-L1 cell

Objective:To explore possible mechanisms of Huanglian Wendan decoction drug-containing serum to improve insulin resistance.Method: 3T3-L1 fibroblasts were divided into control group, model group and TCM group. 3T3-L1 fibroblasts in model group and TCM group were induced to differentiation, and the 3T3-L1 adipocyte model of insulin resistance was constructed. The control group and model group were given normal serum stimulation, while the TCM group is treated with drug-containing serum. Finally, proceed bioinformatics analysis of the acquired differential expression protein by using TMT marking, liquid chromatography-mass (LC-MS) spectrometry, GO analysis and KEGG pathway analysis.Results:4982 proteins are identified in three groups of samples in this experiment, 4238 of them contain quantitative information. 210 up-regulate and 399 down-regulate proteins exist in model group and control group;221 up-regulate and 98 down-regulate ones are identified in TCM group and control group;310 up-regulate and 142 down-regulate proteins come to light with TCM group and control group. The result shows that the differentially expressed proteins were mainly distributed in s GO terms, such as DNA replication, nucleoplasm and protein binding of TCM group and control group. KEGG pathway enrichment analysis shows that, differentially expressed up-regulate proteins were enriched in 10 pathways, for instance DNA replication, cell cycle and mismatch repair, etc. Besides, differentially expressed down-regulate proteins were enriched in 25 pathways, enriched pathways are peroxisome, fatty acid degradation and metabolism process, etc.Conclusion: It is clear that Huanglian Wendan decoction drug-containing serum could improve insulin resistance by multi-targeting, multi-pathway synergy, and overall regulation.

Protective effects of modified Wendan decoction on hippocampal neurons in a rat model of depression

Objective:To study the effects of modified Wendan decoction on hippocampal neuron plasticity in a rat model of depression.Methods:Thirty-two rats were randomly divided into a blank control group,model group,traditional Chinese medicine(modified Wendan decoction)group,and Western medicine(fluoxetine)group.Isolation in conjunction with the chronic unpredictable mild stress(CUMS)method was used to replicate depression in rats from the experimental groups.The rats were treated for 28d following successful modeling.After treatment,transmission electron microscopy(TEM)was used to observe the ultrastructure of hippocampal dentate gyrus(DG)region in the rats.Enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of brain-derived neurotrophic factor(BDNF)and glial cell line-derived neurotrophic factor(GDNF)in hippocampal tissue.Additionally,RT-PCR was used to measure hippocampal BDNF and GDNF mRNA expression levels.Results:Compared to the control group,there was significant swelling,disordered cell arrangement,pyknosis,deepening of cytoplasmic staining in the hippocampal neurons,and severe hippocampal injury in the model group.Following treatment with the traditional Chinese medicine intervention,hippocampal neuronal injury was significantly alleviated,hippocampus structure was normal,and brain injury was significantly reduced in the depression rat model.Compared to the control group,hippocampal BDNF and GDNF mRNA levels in the model group were reduced(P<0.05).Compared to the model group,hippocampal BDNF and GDNF mRNA levels in the traditional Chinese medicine group increased(P<0.05).Conclusion:Modified Wendan decoction can increase hippocampal neurotrophic function and repair hippocampal neuronal injury,thereby preventing depression.

Effect of modified Wendan Decoction on enteric glia cells in depression model rats

Background:To explore the effect of modified Wendan Decoction on expression of enteric glial cells in depression model rats.Methods:Eighteen rats were randomly divided into the Blank group,Model group,and modified Wendan Decoction group(Decoction group).Depression was induced by isolation combined with chronic unpredictable mild stress in rats of all groups except for the Blank group.Changes of protein and mRNA expressions of the specific markers of enteric glial cells,glial fibrillary acidic protein,and S100 calcium-binding proteinβsubunit(S100β)in the stomach and colon tissues of rats in each group were detected respectively using immunohistochemistry and reverse transcription-polymerase chain reaction(RT-PCR).Results:Compared with the Blank group,the percentage of positive cells and the mRNA expression of GFAP and S100βwere increased in the Model group,and the difference was statistically significant(P<0.05);compared with the Model group,the percentage of positive cells and the mRNA expression of GFAP and S100βin gastrointestinal tissues of rats were decreased in the Decoction group,and the difference was statistically significant(P<0.05).Conclusion:The depression model rats developed hyperplasia,and enteric glial cells(EGCs)was activated.The mechanism of action of the Wendan Decoction on improving depression and promoting gastrointestinal motility may be achieved by inhibiting the hyperplasia and activation of EGCs in rats with depression.

国医大师熊继柏治疗失眠的方药规律分析

目的对国医大师熊继柏教授治疗失眠的病案进行数据挖掘,分析熊继柏教授诊治失眠的用方、用药经验。方法基于中医传承辅助平台软件(V3.5),归纳和分析熊继柏教授在湖南中医药大学第一附属医院治疗失眠患者的门诊病历数据,利用该平台软件的关联规则、复杂系统熵聚类等统计方法进行数据挖掘和分析,总结药物的性味、归经、应用频次、药对组合及合方,对“证-症-方”“证-症-药”“证-方-药”进行关联,结合熊继柏教授对失眠病因病机、治则治法的认识,明确核心用药,探索其对失眠的诊治规律及遣方用药心得。结果通过总结分析,共纳入病历276份,处方中用药频次较多的有酸枣仁、龙齿、茯神、甘草,重在补虚安神;黄连、陈皮、竹茹、半夏、珍珠母、远志,重在清热化痰安神。用药性味偏甘、苦、辛,归经多为心、脾经。并归纳出虚证治疗常用合方为酸枣仁汤、枕中丹和甘麦大枣汤;因痰所致失眠治疗的主方为温胆汤及温胆汤类方(枣仁温胆汤、黄连温胆汤及十味温胆汤)。结论国医大师熊继柏治疗失眠以“补脾化痰清热,养血补肝宁心”为治疗原则,以温胆汤为基础进行加减化裁。

温胆汤含药血清对10 mmol/L谷氨酸环境下星型胶质细胞PI3K、Akt、mTOR表达的影响

目的 探讨温胆汤含药血清对10 mmol/L谷氨酸诱导的大鼠星型胶质细胞凋亡、周期及磷脂酰肌醇3-激酶(phosphoinositide 3-kinase, PI3K)、蛋白激酶B(protein kinase B,Akt)、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)表达的影响。方法 将60只SPF级SD雄性大鼠随机分为5组,其中正常组20只,氯氮平组和温胆汤高、中、低剂量组各10只。正常组予20 g/kg 0.9%氯化钠溶液灌胃,氯氮平组予氯氮平原药20 mg/kg灌胃,温胆汤高、中、低剂量组分别予40、20、10 g/kg温胆汤灌胃,1次/d,共8 d。处死大鼠后取血,离心取血清,灭活除菌,EP管分装备用。将大鼠星型胶质细胞分为正常血清组、模型血清组,氯氮平含药血清组和温胆汤高、中、低剂量含药血清组,除正常血清组外,其余各组予10μmol/mL谷氨酸处理48 h后,流式细胞仪检测细胞凋亡和细胞周期;Western bloting、Real-time PCR分别测定细胞PI3K、Akt、mTOR蛋白和mRNA表达。结果 温胆汤含药血清可明显降低谷氨酸环境下大鼠星型胶质细胞凋亡率(P<0.01)和G0/G1期细胞占比(P<0.05),升高S期及G2/M期细胞占比;降低细胞P-P13K/P13K、P-ATK/AKT、P-mTOR/mTOR蛋白表达比值(温胆汤低剂量血清组除外,P<0.05)和细胞PI3K、Akt、mTOR mRNA表达(温胆汤低剂量血清组除外,P<0.01)。结论 温胆汤含药血清可有效调节大鼠星形胶质细胞PI3K、Akt、mTOR表达,达到保护神经细胞的目的,这可能是温胆汤治疗精神分裂症的作用机制之一。

基于IKKβ/NF-κB通路探讨温胆汤对睡眠障碍小鼠的神经保护作用

目的 探讨温胆汤对睡眠障碍小鼠神经损伤的影响及其机制。方法 小鼠采用改良版水平转盘睡眠剥夺法构建失眠模型,造模成功后随机分为模型组、艾司唑仑片组(0.15 mg/kg)和温胆汤低、高剂量组(12.5、50 g/kg),每组6只,另取6只作为对照组。给药干预7 d后,HE染色观察大脑皮层组织、海马CA1区组织、下丘脑组织变化;尼氏染色观察神经元损伤情况;ELISA法检测脑组织和血清中神经丝轻链(NEFL)、神经特异性烯醇化酶(NSE)、S100钙结合蛋白B(S100B)、肿瘤坏死因子(TNF-α)、白细胞介素6(IL-6)、白细胞介素1β(IL-1β)水平;免疫组化法检测脑组织中胶质纤维酸性蛋白(GFAP)表达;Western blot法检测脑组织中GFAP、磷酸化IκB激酶β(p-IKKβ)、磷酸化核转录因子-κB(p-NF-κB)蛋白表达。结果 与模型组比较,温胆汤高剂量组小鼠神经元细胞数量增加,结构完整,排列整齐,神经元细胞核皱缩变形数量减少,尼氏小体增多,血清和脑组织NEFL、NSE、S100B、TNF-α、IL-6、IL-1β水平降低(P<0.01),脑组织GFAP表达降低(P<0.01),脑组织p-IKKβ和p-NF-κB磷酸化水平均降低(P<0.01)。结论 温胆汤能够减少睡眠障碍小鼠的神经损伤,减少促炎介质释放,其机制可能与抑制IKKβ/NF-κB通路的激活有关。

加味黄连温胆汤治疗代谢综合征的临床疗效及其对认知功能的影响

目的:研究加味黄连温胆汤治疗痰瘀互结型代谢综合征(MS)的临床疗效及其对认知功能的影响。方法:选取2022年6月—2023年3月就诊于黑龙江中医药大学附属第一医院心血管一科门诊的MS合并轻度认知功能障碍(MCI)病人70例,运用随机数字表法将其分为两组,对照组采用常规西药治疗,观察组在此基础上联合加味黄连温胆汤。治疗4周后,比较两组病人治疗前后中医证候积分、体质指数(BMI)、收缩压(SBP)、舒张压(DBP)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、空腹血糖(FPG)、血清胰岛素(FINS)及胰岛素抵抗指数(HOMA-IR)、蒙特利尔认知评估量表(MoCA)评分及不良反应发生情况。结果:治疗后两组病人中医证候积分、BMI、SBP、DBP、TG、TC、LDL、FPG、FINS及HOMA-IR水平均较治疗前降低,且观察组明显优于对照组,差异均有统计学意义(P<0.05)。治疗后两组MoCA评分及HDL水平均提高,且观察组优于对照组,差异均有统计学意义(P<0.05)。两组病人治疗中均未发生不良反应。结论:加味黄连温胆汤联合常规西药治疗可有效改善MS合并MCI病人的临床症状,调节糖脂代谢,改善认知功能,且无不良反应。

口服硝黄温胆汤联合益生菌灌肠治疗膀胱癌根治性切除术+回肠原位新膀胱术术后胃肠功能紊乱的临床效果

目的探讨口服硝黄温胆汤联合益生菌灌肠治疗膀胱癌根治性切除术+回肠原位新膀胱术术后胃肠功能紊乱(POGD)的临床效果。方法选取2020年1月至2022年12月佛山市中医院泌尿外科的84例膀胱癌根治性切除术+回肠原位新膀胱术POGD患者为研究对象,采用随机数字表法将其分为对照组及试验组,各42例。两组均给予基础治疗,对照组给予甲硫酸新斯的明注射液肌肉注射联合开塞露塞肛灌肠,试验组口服硝黄温胆汤联合益生菌灌肠。比较两组的治疗效果。结果治疗后,试验组的腹胀、肠鸣音及伴随症状评分低于对照组(P<0.05)。治疗后,试验组的胃泌素(GAS)、胃动素(MOT)水平高于对照组,C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平及白细胞计数(WBC)低于对照组(P<0.05)。试验组的治疗总有效率高于对照组(P<0.05)。结论口服硝黄温胆汤联合益生菌灌肠治疗根治性膀胱全切+回肠原位新膀胱术POGD的临床效果确切。

温胆汤对肥胖代谢相关基因B4 galt7、Sc5d启动子甲基化及表达的影响

目的 分析中医化痰名方温胆汤对肥胖腹腔脂肪组织代谢相关基因B4 galt7、Sc5d启动子区甲基化及表达的影响。方法 首先采用高脂饲料喂养构建肥胖大鼠模型,通过高、中、低不同剂量温胆汤干预肥胖大鼠,观察药物减重降脂的效应;然后采用Massarray技术检测B4Galt7、Sc5d基因启动子甲基化情况;再分别利用实时荧光定量RT-PCR技术、蛋白质印迹技术检测B4Galt7、Sc5d基因的表达情况,分析启动子区甲基化情况与表达间的关系。结果 (1)温胆汤的干预效果与药物浓度无明显剂量依赖关系,高、中剂量温胆汤对肥胖大鼠具有较好减轻体质量作用;温胆汤对改善肥胖大鼠的血脂中TG、TC、LDL-C水平有积极意义,尤其以高剂量组明显。(2)B4 galt7基因启动子区共检测到有31个位点发生甲基化改变。空白对照组与正常对照组比较平均甲基化程度上升,其中有24个位点甲基化程度上升。在此24个位点中,各药物组基本呈现与空白组相对的调控方向,即甲基化程度较空白对照组下降;Sc5d基因启动子区共检测到有37个位点发生甲基化改变。空白对照组与正常对照组比较平均甲基化程度下降,其中有20个位点甲基化程度下降。在此20个位点中,各药物组基本呈现与空白对照组相对的调控方向,即甲基化程度较空白对照组上升。(3)空白对照组与正常对照组相比B4Galt7 mRNA表达降低,但差异无统计学意义(P>0.05);温胆汤干预后,各药物组表达低于空白对照组,但组间均无统计学差异(P>0.05);空白对照组与正常对照组相比Sc5d mRNA表达增高,差异具有统计学意义(P<0.05);温胆汤干预后,各药物组与空白对照组比较表达降低,其中药物中剂量组降低明显,具有统计学差异(P<0.05)。(4)空白对照组与正常对照组比较,B4Galt7、Sc5d蛋白表达升高明显(P<0.01)。温胆汤干预后,各药物组B4Galt7、Sc5d蛋白表达明显低于空白对照组,且差异存在统计学意义(P<0.01)。结论 温胆汤对B4Galt7基因启动子甲基化程度的影响均与其表达无明显关系,而对Sc5d基因启动子的甲基化的影响与其表达有相关性。