Effect of Sijunzi Decoction on the Myonuclear Domain of Rat Soleus in Spleen Qi Deficiency

Objective: To study the mechanism of Sijunzi decoction treating limb weakness in spleen Qi deficiency (SQD) based on the myonuclear domain (MND) theory. Methods: 40 male Sprague-Dawley rats were randomly divided into the normal group, SQD model group (model group), SQD+ still water group (SW group) and SQD+ Sijunzi decoction group (CM group), 10 rats each group;Grip-Strength Meter was used to measure limb grip strength;transmission electron microscope was employed to observe the ultrastructural changes of the myofibers, Image Pro 6.0 was used to measure the myonuclear numbers, cross-section area (CSA) and then their ratios (the MND sizes) were calculated, immunofluorescence assay was chosen to test the expressions of paired box gene 7 (Pax7) and myogenic differentiation antigen (MyoD). Results: Compared with those in the normal group, limb grip strength was decreased, sarcomeres were abnormal, and all the myonuclear numbers, CSA and MND sizes were reduced, but the Pax7+ cell numbers were increased, significantly, in the model and SW groups;Compared with those in the model and SW groups, limb grip strength was increased, sarcomeres were basically normal, the myonuclear number and CSA were both greater, and the Pax7+ and MyoD+ cell numbers were both increased, significantly, in the CM group. Conclusion: Sijunzi decoction might increase the myonuclear number by activating the MSCs to treat limb weakness in SQD.

Research progress on effective chemical constituents of Sijunzi Decoction and mechanism of prevention and treatment of digestive system diseases

Sijunzi Decoction,as one of the classic Chinese traditional prescriptions,has been used clinically by major physicians since the Song Dynasty.This article reviewed and sorted out the literature on the effective chemistry of Sijunzi Decoction and the mechanism of its prevention and treatment of digestive system diseases.At present,its effective chemical components are derived from the saponins and flavonoids in ginseng and licorice,and are effective for gastrointestinal mucosal injury diseases and malignant digestive system.Digestive system diseases such as tumors,functional gastrointestinal diseases,non-alcoholic fatty liver,acute liver injury,and liver failure show a multi-path,multi-target effect mechanism.This article reviews the effective chemical components and research of Sijunzi Decoction and the related mechanisms of prevention and treatment of digestive system diseases,and provides valuable clues for the follow-up research of Sijunzi Decoction.

Determination of Liquiritigenin, Liquiritin, Isoliquiritigenin and Isoliquiritin in Extract of Traditional Chinese Medicine Sijunzi Decoction by High-Performance Liquid Chromatography

Aim An HPLC-UV method for the analysis of Traditional Chinese Medicine （TCM） preparation, Sijunzi decoction, has been developed. Four flavonoid marker compounds, liquiritigenin, liquiritin, isoliquiritigenin, and isoliquiritin, from Radix Glycyrrhizae were quantitatively analyzed in this preparation. Methods The separation was performed on a reversed-phase C18 column by using a gradient elution with mobile phase of （A） water-formic acid （100∶0.04, V/V） （pH 3） and （B） acetonitrile. The mobile phase gradient was set from 0-5 min at 10% of B and 45 min to 90% of B. The assay was carried out at a flow rate of 0.2 mL·min-1 at room temperature with the UV detection wavelengths at 280 nm and 368 nm. Results The extract （25 mg·mL^-1） of Sijunzi decoction contains 1.47 μg·mL^-1 liquiritigenin, 16.40 μg·mL^-1 liquiritin, 0.66 μg·mL^-1 isoliquiritigenin, and 2.12 μg·mL^-1 isoliquiritin. The recoveries for the sample preparation of the markers were 102.2%, 97.7%, 100.3%, and 99.9%, respectively. Conclusion The method is simple and accurate. This study reports a routine quantitative method for the analysis of multiple components in Sijunzi decoction by HPLC.

Total polysaccharides of the Sijunzi decoction attenuate tumor necrosis factor-α-induced damage to the barrier function of a Caco-2 cell monolayer via the nuclear factor-κB-myosin light chain kinase-myosin light chain pathway

AIM To explore the protective effects and underlying mechanisms of total polysaccharides of the Sijunzi decoction(TPSJ) on the epithelial barriers in vitro. METHODS Caco-2 cell monolayers were treated with or without TPSJ in the presence or absence of TNF-α, and paracellular permeability and transepithelial electrical resistance(TEER) were measured to evaluate the epithelial barrier function. Immunofluorescence and western blotting were respecti-vely used to evaluate the distribution and expression of the tight junction proteins claudin 1, claudin 2, zo3, and occludin in Caco-2 cells. western blotting was also used to evaluate the cellular expression of myosin light chain(MLC), phosphorylated MLC(pM LC), MLC kinase(MLCK), and nuclear factor(NF)-κB p65. RESULTS TPSJ promoted the proliferation of Caco-2 cells and inhibited TNF-α-induced secretion of pro-inflammatory cyto-kines. Furthermore, TPSJ significantly ameliorated both the reduction of TEER and the increased paracellular permeability observed in tumor necrosis factor(TNF)-α-damaged Caco-2 monolayers. Furthermore, TPSJ remarkably attenuated TNF-α-induced morphological changes, downregulated the expression of claudin 1, claudin 2, zo3, and occludin, and markedly suppressed TNF-α-mediated upregulation of p-MLC and MLCK expression. Finally, TPSJ inhibited the activation and expression of NF-κB p65. CONCLUSION Our results demonstrate that TPSJ alleviates the TNF-α-induced impairment of the intestinal epithelial cell barrier function by suppressing NF-κB p65-mediated phosphorylation of MLCK and MLC.

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.

Clinical Study of Jiawei Huangqi Guizhi Wuwu Decoction (加味黄芪桂枝五物汤) in Preventing and Treating Peripheral Neuro-sensory Toxicity Caused by Oxaliplatin

Objective： To evaluate the efficacy of Jiawei Huangqi Guizhi Wuwu Decoction （加味黄芪桂枝五物汤, JHGWD） in treating neuro-sensory toxicity induced by oxaliplatin. Methods： A randomized controlled self-crossover trial was performed. Thirty-one patients were randomly divided into AB and BA groups. Patients in A cycle belonged to the treated group, who were treated with chemotherapy combined with oxaliplatin plus JHGWD. Patients in B cycle belonged to the control group and were treated with chemotherapy alone. The peripheral neuro-sensory toxicity was observed and analyzed. Results： The main neurotoxicity was cold-induced paresthesia after the use of oxaliplatin, which included hyperaesthesia, chill, anaesthesia in the extremities, electrified sensation, formication, foreign body sensation and pain that might be exacerbated by exposure to cold. Twenty patients （64.5 % ） suffered from neuro-sensory toxicity in the treated group and 27 cases （87.1% ） in the control group. Symptoms were more serious and lasted longer in the control group than those in the treated group （P〈0.01）. Conclusion： JHGWD could prevent and reduce the occurence and intensity of acute peripheral neuro-sensory toxicity caused by oxaliplatin.

Clinical Observation of Jiawei Buzhong Yiqi Decoction in the Treatment of Obese Polycystic Ovarian Syndrome

[Objectives] To observe the clinical efficacy of Jiawei Buzhong Yiqi Decoction in the treatment of polycystic ovarian syndrome(PCOS).[Methods]Obese patients with PCOS were recruited for the study in September 2014-December 2016 from Chinese medicine gynecological clinic in the affiliated hospital of Hubei University of Medicine.All these patients were given one dose of Jiawei Buzhong Yiqi Decoction one time a day for three months.Body mass index(BMI) was measured before and after treatment.Sex hormone levels and ovulation were measured,and the improvement of clinical symptoms was compared before and after treatment.[Results] After treatment,the levels of BMI and serum luteinizing hormone(LH),testosterone(T) were significantly decreased,and the level of serum estradiol(E2) was significantly higher than that before treatment.Ovarian enlargement and polycystic changes,menstrual cycle,menstrual flow and menstrual period were improved in varying degrees.[Conclusions] Jiawei Buzhong Yiqi Decoction has a good clinical effect in the treatment of obese PCOS.

Efficacy and safety of Sijunzi Decoction for peptic ulcers: A systematic review and meta-analysis

Objective:To investigate the therapeutic efficacy and safety of Sijunzi Decoction (SJZD) for peptic ulcers (PUs) through the assessment of randomized controlled tHals (RCTs).Methods:Five English and four Chinese databases were systematically searched to identify eligible RCTs that investigated the effect of SJZD for PUs.SJZD was used either independently or concomitantly with routine anti-ulcer treatments and compared with no intervention,placebo,or conventional therapy.Outcomes evaluated included ulcer healing,symptom improvement,Helicobacter pylori (Hp) eradication,ulcer recurrence,and adverse reactions.Statistical analysis and risk of bias was evaluated by Revman 5.3.Results:Fourteen trials involving 1476 participants fulfilled the selection criteria.All trials were presented with a high risk of bias.Analyses showed that modified SJZD had significant benefit on ulcer healing compared with ranitidine and sucralfate and triple therapy with omeprazole,amoxicillin and clarithromycin.Compared with this omeprazole triple therapy and therapy using pantoprazole,the addition of modified SJZD was superior.Regarding symptom improvement,modified SJZD was significantly better than ranitidine and sucralfate and had an added benefit when supplemented with either of two omeprazole triple therapies (omeprazole,amoxicillin and clarithromycin,and omeprazole,levofloxacin and furazolidone) or pantoprazole.Furthermore,modified SJZD had a favorable effect on Hp eradication compared with cimetidine and additional benefit was noted when complemented with either of the two omeprazole triple therapies or therapy consisting of omeprazole and amoxicillin.Modified SJZD was superior at reducing ulcer recurrence among healed patients compared with cimetidine.Modified SJZD with triple-drug regimen comprising omeprazole,amoxicillin and clarithromycin was also found to be more effective at reducing ulcer relapse compared with the triple therapy alone.No serious adverse events were reported.Conclusion:Modified SJZD,used independently or as a complementary treatment to conventional ulcer-healing treatments,promoted PU healing,alleviated symptoms,eradicated Hp,and reduced ulcer relapse.Modified SJZD was relatively safe.However,rigorous randomized controlled trials are required to provide further support for these effects because of the high risk of bias and limited sample size of the included trials.

The therapeutic effect of Jiawei Danshen Decoction on myocardial ischemia-reperfusion injury by inhibiting H_(2)S-mediated autophagy signaling pathway

Objective To investigate the protective effects of Jiawei Danshen Decoction(加味丹参饮,JWDSD)on myocardial ischemia-reperfusion injury(MIRI)via the regulation of serum Hydrogen sulfide(H2S)and cardiac Beclin1,light Chain 3 A/B(LC3 A/B),p62,and autophagy protein5(ATG5).Methods Seventy specific pathogen free(SPF)Sprague-Dawley(SD)rats were randomly assigned to seven groups(n=10 in each group),including normal control,sham operation,MIRI model(model),ischemic preconditioning,Na HS,JWDSD,and JWDSD+CSE inhibitor(JWDSD+PPG)groups,and orally administered the indicated drugs for 14 d.Two hours after the last administration,the left anterior decreased branch of the coronary artery of each rat in model,Na HS,JWDSD,and JWDSD+PPG groups was ligated for 30 min and subsequently reperfused for 90 min to establish the MIRI model,and the rats in the sham operation group were only exposed to the thorax after surgery without coronary ligation.Blood samples were collected to detect H2S levels using an enzyme-linked immunosorbent assay(ELISA).Heart tissues were harvested for histopathological and immunohistochemical examination and quantitative reverse transcription polymerase chain reaction analysis of Beclin1 and ATG5 m RNA expression and Western blot analysis of Beclin1,LC3 A/B,and p62 protein expression.Results(1)The serum H2S content in model group rats was significantly reduced(P<0.01),JWDSD significantly increased the serum H2S content of model group rats(P<0.01),and the CSE inhibitor(PPG)significantly reduced H2S levels in the JWDSD group rats(P<0.01).(2)Compared with the normal control group,the myocardial tissue necrosis and cell destruction occurred in the MIRI model group,and JWDSD could alleviate the myocardial tissue necrosis of model rats,but the ameliorative effect of JWDSD could be reversed by PPG.(3)Beclin1,LC3 A/B,and p62 expression levels in the heart tissues of the model group were significantly increased(P<0.001),whereas decreased by JWDSD(P<0.05,P<0.01,and P<0.001,respectively),and the inhibitory effects of JWDSD on Beclin1,LC3 A/B,and p62 expression were partially reversed by PPG(P<0.01,P<0.05,and P<0.01,respectively).(4)The expression levels of autophagy-related genes Beclin1 and ATG5 were significantly increased in the model group(P<0.001).JWDSD clearly downregulated the expression levels of Beclin1 and ATG5(P<0.05 and P<0.001,respectively),which were reversed by PPG(P<0.001).Conclusion Our experimental data show that JWDSD can exhibit an anti-MIRI role by increasing endogenous H2S generation,and downregulating the expression of Beclin1,LC3 A/B,p62 and ATG5,which are related to inhibiting autophagy signaling.

Effects of Jiawei Buzhong Yiqi Decoction on the Endometrial Receptivity of Rats with Polycystic Ovary Syndrome

[Objectives]The study aims to discuss the effects of Jiawei Buzhong Yiqi Decoction on the endometrial receptivity of rats with polycystic ovarian syndrome(PCOS).[Methods]Adult female SD rats were selected and randomly divided into the model group and control group.In the model group,the PCOS model was established by using the method of Poretsky L.Rats in the control group were given physiological saline intervention at the same time.The successfully modeled rats were randomly divided into the PCOS group and traditional Chinese medicine group.Among them,rats in the Chinese medicine group were given Jiawei Buzhong Yiqi Decoction by gavage;rats in the model group and the control group were given normal saline for 14 d.All rats were killed by anesthesia after the last administration,and serum and uterine specimens were collected.Serum sex hormones(including T,E_(2),and P),glucose and insulin levels were detected;the equivalent diameter and area of endometrial gland and gland cavity,and the endometrial thickness of rats were measured;the expression of endometrial leukemia inhibitory factor(LIF),integrinαvβ3 protein and mRNA was detected by using Elisa and RT-PCR methods.[Results]The serum T,glucose,and insulin levels of rats in the PCOS group were significantly higher than those of the control group and the traditional Chinese medicine group,and there was no significant difference in the above indicators between the control group and the traditional Chinese medicine group;there was no significant difference in the E_(2) and P levels between the three groups.The equivalent diameter and area of endometrial gland and gland cavity,and the endometrial thickness of rats in the PCOS group were lower than those of the control group and the traditional Chinese medicine group;there was no significant difference in the above indicators between the traditional Chinese medicine group and the control group.The expression of LIF,integrinαvβ3 protein and mRNA in the endometrium of rats in various groups was basically the same.The expression of LIF and integrinαvβ3 in the endometrium of rats in the PCOS group was significantly lower than that of the control group and the traditional Chinese medicine group;there was no significant difference in the above indicators between the control group and the traditional Chinese medicine group.[Conclusions]The endometrial receptivity of PCOS rats was decreased;Jiawei Buzhong Yiqi Decoction can improve the endometrial receptivity of PCOS rats by increasing the expression of LIF and integrinαvβ3 in the endometrium.

Effect of Sijunzi decoction combined with nutritional support after gastric cancer surgery on the stress inflammatory response and immune response

Objective:To study the effect of Sijunzi decoction combined with nutritional support after gastric cancer operation on the stress inflammatory response and immune response.Methods:Patients who received radical operation for gastric cancer in West China Hospital between March 2015 and August 2017 were selected and randomly divided into the observation group who accepted Sijunzi decoction combined with enteral nutrition support after operation and the control group who accepted routine enteral nutrition support after operation. The stress inflammatory response indexes in serum and the immune response indexes in peripheral blood were measured before operation and 3 d after operation.Results: 3 d after operation, Cor, Gluc, Ins, O2-, CRP, TNF-α, YKL-40, MK and IL-6 contents in serum as well as GATA-3, RORγt and Foxp3 expression in peripheral blood of both groups were higher than those before operation whereas HO-1 and SOD contents in serum as well as CD3+CD4+T cell, CD3+CD8+T cell, CD16+CD56+NK cell and CD19+B cell contents and T-bet expression in peripheral blood were lower than those before operation, and Cor, Gluc, Ins, O2-, CRP, TNF-α, YKL-40, MK and IL-6 contents in serum as well as GATA-3, RORγt and Foxp3 expression in peripheral blood of observation group were lower than those of control group whereas HO-1 and SOD contents in serum as well as CD3+CD4+T cell, CD3+CD8+T cell, CD16+CD56+NK cell and CD19+B cell contents and T-bet expression in peripheral blood were higher than those of control group.Conclusion: Sijunzi decoction combined with nutritional support after gastric cancer operation can reduce the stress inflammatory response and enhance the immune response.

Therapeutic Effect of Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)with Acupoint Application on Chronic Lumbar Muscle Strain and the Recovery of Lumbar Strength

Objective:To study the therapeutic effect of Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)with acupoint application on chronic lumbar muscle strain and the recovery of lumbar strength.Methods:From August 2018 to August 2019,100 patients with chronic lumbar muscle strain admitted to our hospital were selected and randomly divided into an acupoint application group and a combined group of 50 cases each.The acupoint application group was treated by acupoint application,and the combined group was treated with Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)based on acupoint application.The indexes scores,VAS scores,ADL scores,ODI scores,lumbar endurance,TCM syndrome scores and the treatment effects of the two groups before and after treatment were statistically analyzed,and TNF-αand TXB2 levels were detected.Results:After treatment,the scores of indexes,VAS,ODI,TCM syndrome,TNF-αand TXB2 in the combined group were lower than those in the acupoint application group,and the ADL score,lumbar endurance and treatment efficiency were higher than those in the acupoint application group,with a statistical difference(P<0.05).Conclusion:Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)with acupoint application can effectively reduce pain,improve lumbar function,restore lumbar strength,effectively relieve inflammation,with significant effects.

基于TNF-α/NF-κB通路探讨四君子汤对快速衰老型小鼠海马神经元炎症因子调节自噬蛋白的作用机制研究

目的 探讨四君子汤(Sijunzi decoction,SJZD)对快速衰老型(senescence-accelerated mouse prone 8,SAMP8)小鼠海马组织炎症因子、自噬蛋白表达的影响及作用机制。方法 将SAMR1小鼠作为对照组、32只SAMP8小鼠分为模型组、多奈哌齐组(Donepezil)、SJZD低、高剂量治疗组。采用Y字迷宫实验检测小鼠记忆功能的变化;免疫组化法检测NF-κB蛋白表达变化;ELISA法检测肿瘤坏死因子(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)含量;Western blot法检测海马组织Aβ蛋白、caspse-1、beclin-1、LC3-II蛋白表达。结果 与对照组比较,模型组小鼠总进臂次数减少、交替次数减少,TNF-α、IL-1β、IL-6含量升高,Aβ蛋白、caspse-1蛋白表达上调,beclin-1蛋白及LC3-II蛋白表达下调;Donepezil与模型组比较,总进臂次数增加,交替次数增加,IL-6含量减少,Aβ蛋白表达下调。SJZD低剂量组和高剂量组,与模型组比较,总进臂次数增加,交替次数增加;TNF-α、IL-1β、IL-6、Aβ蛋白、caspase-1含量降低;beclin-1、LC3-II蛋白表达上调。结论 四君子汤治疗阿尔茨海默病可能与纠正中枢海马相关炎症因子及自噬功能失调有关。

加味百合地黄汤对围绝经期抑郁症模型大鼠HPO轴和雌激素受体表达的影响

目的基于下丘脑-垂体-卵巢(hypothalamic-pituitary-ovarian,HPO)轴及雌激素受体(estrogen receptor,ER)探明加味百合地黄汤治疗围绝经期抑郁症的功效及潜在机制。方法将大鼠随机分为正常对照组、模型组、阳性药物组(氟哌噻吨美利曲水溶液1.89 mg/kg)以及加味百合汤高、中、低剂量组(16.2 g/kg、8.1 g/kg、4.05 g/kg),每组10只。除正常对照组外,其他组均采用双侧卵巢摘除联合慢性不可预见性应激建立围绝经期抑郁症大鼠模型。各组给药21 d后采用糖水偏好实验和强迫游泳实验评价大鼠抑郁样行为,酶联免疫吸附法检测血清促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)、卵泡刺激素(follicle-stimulating hormone,FSH)、黄体生成素(luteinizing hormone,LH)、雌二醇(estradiol,E2)含量,HE染色观察下丘脑、垂体、海马等组织病理损伤情况,RT-PCR和Western blot法检测下丘脑、海马组织雌激素受体基因及蛋白的表达。结果与正常对照组比较,模型组大鼠糖水偏好度显著下降(P<0.01),强迫游泳不动时间显著增加(P<0.01),表现出明显抑郁样行为,血清GnRH、FSH、LH含量均显著升高(P<0.01或P<0.05),E2降低(P<0.01),下丘脑、垂体及海马组织受损,雌激素受体表达显著降低(P<0.01);经加味百合地黄汤干预治疗后,模型组大鼠抑郁样行为显著改善(P<0.01或P<0.05),HPO轴亢进状态及海马损伤得以缓解,下丘脑、海马雌激素受体表达均显著增加(P<0.01或P<0.05)。与阳性药物组比较,加味百合地黄汤高剂量组下丘脑雌激素受体基因表达显著增加(P<0.05)。结论加味百合地黄汤通过抑制HPO轴亢进及增加脑内雌激素受体水平,发挥抗围绝经期抑郁症作用。

加味消癥方对慢性肾衰竭大鼠肾纤维化的保护作用及对肾小管上皮细胞TGF-β_(1)/Smad3信号通路的影响

目的:探讨加味消癥方对慢性肾衰竭大鼠肾纤维化的保护作用及对肾小管上皮细胞TGF-β_(1)/Smad3信号通路的作用影响。方法:观察加味消癥方对慢性肾衰竭大鼠的血肌酐、尿素氮、24 h尿蛋白定量、肾脏病理及肾组织中FN1、Col-Ⅰ、Col-Ⅲ表达水平的影响;观察加味消癥方对TGF-β_(1)诱导肾小管细胞损伤中TGF-β_(1)、Smad3、LC3、Beclin1及P62蛋白表达的影响。结果:与模型组相比,加味消癥方高剂量组的Scr水平及加味消癥各组和缬沙坦组的24 h尿蛋白水平显著降低(P<0.05,P<0.01);实时荧光定量PCR法检测提示加味消癥方高剂量组的FN1、Col-ⅠmRNA相对表达量、加味消癥方中剂量组和缬沙坦组的Col-ⅢmRNA相对表达量、高剂量组和缬沙坦组的TGF-β_(1)mRNA相对表达量以及高、中、低剂量组和缬沙坦组的Smad3 mRNA相对表达量均较模型组显著降低(P<0.05,P<0.01);Western Blot法检测提示加味消癥方高、中剂量组和缬沙坦组的FN蛋白表达量、加味消癥方高剂量组的Col-Ⅰ蛋白表达量、加味消癥方高、低剂量组和缬沙坦组的Col-Ⅲ蛋白表达量以及高、中剂量组的Beclin1蛋白表达量均较模型组显著降低(P<0.05,P<0.01);Masson染色观察加味消癥方高剂量组的肾间质纤维化程度显著减轻(P<0.01)。此外,该组的48 h/72 h细胞存活率显著升高(P<0.01)。结论:加味消癥方可有效提升细胞存活率,改善肾间质纤维化程度保护肾功能,可能是通过TGF-β_(1)/Smad3通路调控自噬水平,下调FN1、Col-Ⅰ、Col-Ⅲ水平实现的。

基于Caspase-3/Bcl-2/Bax信号通路探究加味旋覆代赭汤治疗食管癌前病变的作用机制

目的:探究加味旋覆代赭汤对食管癌前病变大鼠Caspase-3/Bcl-2/Bax信号通路的调控作用机制。方法:将48只雄性SD大鼠随机分为4组,空白组、模型组、中药组、西药组,每组各12只。除空白组外均采用复合造模法制作食管癌前病变大鼠模型,造模成功后,分别进行药物灌胃干预,空白组、模型组用生理盐水灌胃,中药组和西药组分别给予加味旋覆代赭汤、西药(雷贝拉唑+莫沙必利)灌胃,给药8周取材。利用光学显微镜观察食管上皮组织的形态学变化;分别应用蛋白质印迹法(Western-blot)及聚合酶链式反应(PCR)检测食管上皮组织Caspase-3、Bcl-2及Bax的表达水平。结果:与空白组比较,模型组大鼠食管上皮病理积分升高(P<0.01);与模型组比较,中药组、西药组大鼠食管上皮病理积分均降低(P<0.01)。PCR及Western-blot检测结果显示,与空白组比较,模型组大鼠Caspase-3、Bax mRNA、蛋白表达均降低(P<0.01);与模型组比较,中药、西药组大鼠Caspase-3、Bax mRNA、蛋白表达均增高(P<0.05)。与空白组比较,模型组大鼠食管组织中Bcl-2 m RNA及蛋白表达水平均升高(P<0.05);与模型组比较,中药组和西药组Bcl-2 mRNA及蛋白表达水平均降低(P<0.05)。结论:加味旋覆代赭汤可能通过下调Bcl-2/Bax比值,增加线粒体外膜通透性,释放凋亡因子,激活Caspase-3,使病变组织发生凋亡,扭转食管上皮异型增生,从而起到治疗食管癌前病变的作用。

肠内营养联合四君子汤对消化道肿瘤术后临床疗效的Meta分析

目的:系统评价肠内营养联合四君子汤对消化道肿瘤术后的临床疗效及其安全性。方法:通过计算机检索相关外文电子数据库:Cochrane图书馆、PubMed数据库和EMbase数据库,以及国内中文数据库:中国生物医学文献数据库、中国知网、重庆维普科技数据库和万方数据等,并手工检索无电子版的杂志增刊和会议论文来收集文献。筛选并纳入肠内营养联合四君子汤用于消化道肿瘤术后的临床随机对照试验,文献语种限定为中文或者英文,所有检索时间范围为各数据库建库至2022年10月1日。由两名研究人员各自独立对文献资料的各项数据进行提取,并完成对文献资料的方法学质量评价和结果分析,采用RevMan5.2.3软件进行Meta分析。结果:本次研究共纳入13个临床随机对照试验研究,研究质量均不高。Meta分析结果显示肠内营养联合四君子汤在改善消化道肿瘤术后患者的细胞免疫指标、体液免疫指标、营养指标均高于单独使用肠内营养治疗(P <0.05),而不良反应发生率的差异无统计学意义(P> 0.05)。结论:由于纳入文献篇目较少,文献质量不统一,且原始文献均为中文文献,当前的证据还不能确认该治疗方式在临床实践中是否完全有效,但是从目前的研究来看,其疗效优势值得进一步探究,尤其需要进行高质量的多中心大样本随机双盲对照试验来验证其疗效。

加味补中益气汤治疗哮喘机制的分子对接研究

目的运用分子对接技术预测加味补中益气汤治疗哮喘的作用机制。方法依托中药系统药理学数据库平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP),筛选出加味补中益气汤的主要化学成分和相应靶点,利用Cytoscape软件构建“药物-疾病-靶点”的网络关系,将药物主要成分及疾病的交集靶点导入STRING平台构建蛋白相互作用(Protein-protein interaction networks,PPI)网络,并利用AutoDock软件将加味补中益气汤的主要成分与哮喘的关键靶点进行分子对接。结果共筛选出加味补中益气汤有效成分338种,支气管哮喘相关靶点1744个,其中交集靶点120个。PPI网络分析加味补中益气汤主要作用于蛋白激酶Cα(Protein kinase C alpha,PRKCA)、丝裂原活化蛋白激酶14(Mitogen-activated protein kinase 14,MAPK14)、V-Rel网状内皮增生病毒癌基因同源物A(V-Rel reticuloendotheliosis viral oncogene homolog A,RELA)、V-Jun肉瘤病毒17癌基因同源物(V-Jun sarcoma virus 17 oncogene homolog,JUN)和B细胞中κ轻型多肽基因增强子的核因子15(Nuclear factor-k-gene binding15,NFKB15)个核心靶点。分子对接结果表明筛选得到的主要活性成分与靶点有较强的结合。结论加味补中益气汤治疗支气管哮喘或许具有积极作用,其作用机制可能与调节PRKCA、MAPK14、RELA、JUN和NFKB1等信号通路有关。

加味理肠饮治疗肝郁脾虚型腹泻型肠易激综合征临床研究

目的:观察加味理肠饮治疗肝郁脾虚型腹泻型肠易激综合征(IBS-D)的疗效及对主要症状、疾病相关评分、炎症表现的影响。方法:将60例肝郁脾虚型IBS-D患者按随机数字表法分为中药复方组和西药组各30例,中药复方组给予加味理肠饮治疗,西药组给予利福昔明片,两组均持续治疗2周,治疗结束后4周进行随访。主要疗效指标为治疗2周后(治疗后)和治疗结束4周后(随访时)的有效应答率,即最严重腹痛评分的平均值较基线期改善30%且排便日记中6型或7型Bristol粪便天数较基线期减少50%的患者百分比。次要结局指标包括每周稀便天数、每周平均腹痛评分、IBS症状严重程度量表(IBS-SSS)评分、IBS专用生活质量问卷(IBS-QOL)评分、中医症状评分、血清炎症因子水平、结肠及回肠末端黏膜组织病理形态。结果:两组治疗后及随访时的有效应答率比较,差异无统计学意义(P>0.05)。与治疗前比较,两组患者治疗后及随访时每周稀便天数均减少(P<0.01),每周平均腹痛评分均降低(P<0.01),IBS-SSS、IBS-QOL、中医症状评分均改善(P<0.01);两组患者治疗后血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、P物质(SP)水平较治疗前均降低(P<0.01)。随访时,中药复方组每周稀便天数少于西药组(P=0.046),IBS-SSS评分优于西药组(P<0.01);治疗后及随访时,中药复方组IBS-QOL、中医症状评分均优于西药组(P<0.01);治疗后,西药组血清TNF-α水平低于中药复方组(P<0.01)。随访时,两组患者结肠及回肠末端黏膜组织绒毛结构完整,排列整齐,无炎症细胞浸润。结论:加味理肠饮能减轻肝郁脾虚型IBS-D患者的腹痛、腹泻症状,降低患者血清炎症因子水平,缓解肠黏膜组织低度炎症反应,作用较持久。

四君子汤调控AMPK-SIRT1蛋白改善运动性疲劳小鼠学习记忆的机制研究

目的:观察四君子汤对运动性疲劳(EF)小鼠AMPK/SIRT1信号通路的影响,并探讨其改善EF认知损伤和学习记忆能力的机制。方法:将60只C57BL/6小鼠随机分为空白组、模型组、四君子汤高剂量组、四君子汤中剂量组、四君子汤低剂量组。除空白组外,其他各组小鼠构建脾气虚证EF小鼠模型。四君子汤高、中、低剂量组小鼠分别给予不同浓度的四君子汤灌胃,空白组和模型组以等体积蒸馏水灌胃,各组连续灌胃4周。采用Morris水迷宫实验评估小鼠的认知功能,采用ELISA法检测小鼠血清中乳酸、血糖、肝糖原、肌糖原的水平,Western Blot法检测小鼠脑组织中AMPK和SIRT1的蛋白表达量。结果:实验后,模型组小鼠体质量、摄食量、血糖、肝糖原含量、肌糖原含量、目标象限游泳时间、穿越平台次数、AMPK蛋白表达量、SIRT1蛋白表达量低于空白组,血清乳酸水平高于空白组(P<0.05)。给药干预后,四君子汤高、中、低剂量组小鼠体质量、摄食量、力竭游泳时间、肝糖原含量、肌糖原含量、目标象限游泳时间、穿越平台次数高于模型组,血清乳酸水平低于模型组(P<0.05)。四君子汤高剂量小鼠游泳力竭时间高于低剂量组,乳酸水平低于低剂量组(P<0.05)。四君子汤高、中剂量组肝糖原、肌糖原含量高于低剂量组(P<0.05)。与模型组比较,四君子汤高、中剂量组AMPK及SIRT1蛋白表达量增多(P<0.05),四君子汤低剂量组SIRT1蛋白表达量增多(P<0.05)。与四君子汤低剂量组比较,四君子汤高、中剂量组AMPK及SIRT1蛋白表达量增多(P<0.05)。结论:四君子汤可在一定程度调控AMPK/SIRT1的活性,进而改善EF小鼠脾虚症状。