Model informed precision medicine of Chinese herbal medicines formulas-A multi-scale mechanistic intelligent model

Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets between complex diseases and CHM formulas,we developed an artificial intelligence-based quantitative predictive algorithm(DeepTCM).DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling,molecular and theoretical levels of traditional Chinese medicine(TCM).As an example,our model simulated the optimal CHM formulas for the treatment of coronary heart disease(CHD)with depression,and through model sensitivity analysis,we calculated the balanced scoring of the formulas.Furthermore,we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions.Finally,we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice.This novel multiscale model opened up a new avenue to combine“disease syndrome”and“macro micro”system modeling to facilitate translational research in CHM formulas.

Analysis of Adverse Reactions in the Treatment of COVID-19 with Three Chinese Patent Medicines and Three Herbal Formulas

Objective To explore the rules and characteristics of the adverse drug reactions(ADRs)of three Chinese patent medicines and three herbal formulas for the treatment of COVID-19,and to provide a reference for clinical safe medication.Methods The cases and ADR reports of the three Chinese patent medicines and three herbal formulas in PubMed,Web of Science,Springer Link,CNKI,Wanfang and VIP database were retrieved from December 2019 to May 2021.Then we extracted and analyzed the effective information included in the literature.Results and Conclusion According to the pre-developed retrieval plan,a total of 136 documents were obtained,and a total of 6 documents met the inclusion criteria finally.553 patients used three Chinese patent medicines and three herbal formulas,and there were 133 cases of adverse reactions.The adverse reactions of patients taking the three Chinese patent medicines and three herbal formulas can all be explained under the theory of traditional Chinese medicine,and the adverse reactions can be eliminated by adding or subtracting the flavor of the medicine or stopping the medicine.

Progress on traditional Chinese medicine in improving hepatic fibrosis through inhibiting oxidative stress

Hepatic fibrosis is a common pathological process that occurs in the development of various chronic liver diseases into cirrhosis and liver cancer,characterized by excessive deposition of the extracellular matrix.In the past,hepatic fibrosis was thought to be a static and irreversible pathological process.In recent years,with the rapid development of molecular biology and the continuous in-depth study of the liver at the microscopic level,more and more evidence has shown that hepatic fibrosis is a dynamic and reversible process.Therefore,it is particularly important to find an effective,simple,and inexpensive method for its prevention and treatment.Traditional Chinese medicine(TCM)occupies an important position in the treatment of hepatic fibrosis due to its advantages of low adverse reactions,low cost,and multi-target effectiveness.A large number of research results have shown that TCM monomers,single herbal extracts,and TCM formulas play important roles in the prevention and treatment of hepatic fibrosis.Oxidative stress(OS)is one of the key factors in the occurrence and development of hepatic fibrosis.Therefore,this article reviews the progress in the understanding of the mechanisms of TCM monomers,single herbal extracts,and TCM formulas in preventing and treating hepatic fibrosis by inhibiting OS in recent years,in order to provide a reference and basis for drug therapy of hepatic fibrosis.

Therapeutic potential of natural compounds from Chinese medicine in acute and subacute phases of ischemic stroke

Stroke is one of the leading causes of death and disability in adults worldwide,resulting in huge social and financial burdens.Extracts from herbs,especially those used in Chinese medicine,have emerged as new pharmaceuticals for stroke treatment.Here we review the evidence from preclinical studies investigating neuroprotective properties of Chinese medicinal compounds through their application in acute and subacute phases of ischemic stroke,and highlight potential mechanisms underlying their therapeutic effects.It is noteworthy that many herbal compounds have been shown to target multiple mechanisms and in combinations may exert synergistic effects on signaling pathways,thereby attenuating multiple aspects of ischemic pathology.We conclude the paper with a general discussion of the prospects for novel natural compound-based regimens against stroke.

Effects of Nano Chinese Herbal Medicine Feed Additive on Growth Performance,Meat Quality and Disease Resistance of Chickens

[Objectives]To explore the effects of nano compound Chinese herbal medicine feed additive on growth performance,meat quality and disease resistance of chickens.[Methods]Chickens were fed with nano compound Chinese herbal medicine feed additive developed by Hunan Polytechnic of Environment and Biology,including 120 chickens in the treatment group and 120 chickens in the control group(CK).The growth performance indices(body weight gain,feed to gain ratio and slaughter index),meat quality indices(pH value,color,drip loss,shear force)and disease resistance indices(morbidity and mortality)of the chickens in the treatment and CK groups were recorded and determined,respectively.[Results]The inclusion of 2%nano compound Chinese herbal medicine feed additive in the diet significantly increased the growth rate,reduced the feed-to-gain ratio and improved the meat quality of the chickens.Supplementing Chinese herbal medicine could increase the pH value and reduce the drip loss and shear force of chicken meat.At the same time,the body's immune function,antioxidant level and resistance against diseases of the chickens fed with nano compound Chinese herbal medicine feed additive were improved.[Conclusions]The inclusion of nano compound Chinese herbal medicine feed additive in the diet can improve the growth performance,meat quality and disease resistance of chickens.

Antibacterial Effects of Chinese Herbal Medicines against Streptococcus iniae in Oreochromis niloticus

In this study, the antibacterial effects of Chinese herbal medicines against Streptococcus iniae in Oreochromis niloticus were investigated by drug sensitiv- ity test. The results indicated that Streptococcus in/ae was extremely sensitive to Calla Chinensis, Fructus Hippophae and Fructus Murne, highly sensitive to Sappan Lignum, Pericarpium Granati, Folium Eucalypti and Radix Scutellariae, moderately sensitive to Rh/zoma Coptidis, Radix et Rhizoma Rhei, Flos Caryophyllata, Cortex phellodendri and Rabdosia serra （ Maxim. ） Hara, and insensitive to Herba Portulacae , Herba Houttuyniae , Polygonum hydropiper L. , Herba Menthae , Radix Glycyrrhizae , Pericarpium Citri Reticulatae , Herba Andrographitis and Rhizoma Acori Tatarinowii. Chinese medicinal herbs which Streptococcus iniae was extremely sensitive or moderately sensitive to were selected and prepared into three Chinese herbal medicine formulae for medicated bath of Oreochromis niloticus infected arti- ficially with Streptococcus iniae. The results showed that medicated bath elicited therapeutic effects on infected Oreochromis niloticus. Formula II exhibited the best therapeutic effect with an effective percentage of 90%.

Chinese herbal formulae defend against Mycoplasma gallisepticum infection

Mycoplasma gallisepticum HS strain(MG-HS)is a pathogen that causes chronic respiratory disease(CRD)in chicken,which is characterized by host respiratory inflammatory damage,brings huge economic losses to the poultry industry.Recently,emerging Chinese herbal medicines(CHM)have been used to treat CRD.This study was aimed to investigate the preventive and therapeutic effects and their potential mechanisms of Chinese herbal medicinal formulae(CHMF),which consisted of 10 kinds of Chinese herbal medicine including Scutellaria,Houttuynia cordate and licorice,on MGinduced CRD in chickens.With respect to the preventive effect,the results showed that CHMF could effectively recover the MG-induced decrease on body weight and feed conversion ratio.Histopathological analysis showed that both prevention and treatment of CHMF could significantly alleviate the severe respiratory inflammation induced by MG infection.Moreover,compared with the MG infection group,both the prevention groups and the treatment groups of CHMF could effectively reduce the expression of MG adhesion protein(p MGA1.2)to inhibit the proliferation of MG,and thus effectively inhibit the expression of MG-induced inflammatory factors interleukin-1β(IL-1β)and tumour necrosis factor-α(TNF-α).In summary,these findings confirm that CHMF can protect chickens from various tissue damage caused by MG infection and has no adverse effects on the performance of chickens in the short term.And its efficacy against MG is equal to or better than that of tiamulin.

Compound Formula Rehmannia alleviates levodopainduced dyskinesia in Parkinson's disease

Compound Formula Rehmannia has been shown to be clinically effective in treating Parkinson＇s disease and levodopa-induced dyskinesia; however, the mechanisms remain unclear. In this study, we established a model of Parkinson＇s disease dyskinesia in rats, and treated these animals with Compound Formula Rehmannia. Compound Formula Rehmannia inhibited the increase in mRNA expression of N-methyl-D-aspartate receptor subunits 1 and 2 and excitatory amino acid neurotransmitter genes, and it inhibited the reduction in expression of γ-aminobutyric acid receptor B1, an inhibitory amino acid neurotransmitter gene, in the corpus striatum. In addition, Compound Formula Rehmannia alleviated dyskinesia symptoms in the Parkinson＇s disease rats. These experimental findings indicate that Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson＇s disease by modulating neurotransmitter signaling in the corpus striatum.

Epigastric pain syndrome: What can traditional Chinese medicine do? A randomized controlled trial of Biling Weitong Granules

BACKGROUND Recent research suggests that although prokinetic agents,acid suppressors,and radical treatment for Helicobacter pylori infection may be effective in patients with functional dyspepsia(FD),a large proportion of patients still fail to respond to these treatments or may suffer from severe adverse reactions.Many traditional Chinese medicinal herbs can regulate the status of the entire body and have special advantages in the treatment of functional diseases.The present study was designed to verify the efficacy of Biling Weitong Granules(BLWTG),a traditional Chinese medicinal herbal compound formula,in alleviating epigastric pain syndrome(EPS)in FD patients,in an attempt to provide an effective prescription for the clinical treatment of this disease.AIM To evaluate the clinical efficacy and safety of BLWTG in treating EPS in patients with FD.METHODS In this multicenter,stratified,randomized,double-blind,placebo-controlled,parallel group clinical trial,eligible patients were randomized into the BLWTG and placebo groups who were treated for 6 wk.Efficacy indicators including the severity and frequency of EPS and the time to pain resolution and safety indicators including adverse events were observed and compared.RESULTS The baseline demographic data and clinical characteristics,such as epigastric pain symptoms,pain intensity,and frequency of attacks,were matched between the two groups before randomization.After 6 wk of treatment and after the center effect was eliminated,the epigastric pain was significantly improved in 28.33%and 85.59%of the patients in the placebo and BLWTG groups,respectively(P<0.05).At 6 wk,the resolution rate of epigastric pain was 15%and 69.49%in the placebo and BLWTG groups,respectively(P<0.05).The differences of total FD clinical score between these two groups were significant(P<0.05)at 2,4,and 6 wk(P<0.05).The scores of each item and the total score in the Functional Digestive Disorders Quality of Life Questionnaire showed significant differences between the two groups at 6 wk after both the center and interaction effects were eliminated(P<0.05).There was no significant difference in the incidence of adverse events between the two groups,and no serious adverse event was noted during the observation.CONCLUSION Compared with placebo,BLWTG markedly improved EPS in FD patients without causing serious adverse reactions.

Traditional Chinese medicine for prevention and treatment of hepatocarcinoma: From bench to bedside

Traditional Chinese medicine(TCM) has played a positive role in the management of hepatocarcinoma. Hepatocarcinoma patients may present Qi-stagnation, damp-heat, blood stasis, Qi-deficiency, Yin-deficiency and other TCM syndromes(Zheng). Modern treatments such as surgery, transarterial chemoembolization(TACE) and high intensity focus ultrasound treatment would influence the manifestation of TCM syndromes. Herbs with traditional efficacy of tonifying Qi, blood and Yin, soothing liver-Qi stagnation, clearing heat and detoxifying and dissolving stasis, have been demonstrated to be potent to prevent hepatocarcinogenesis. TCM has been widely used in all aspects of integrative therapy in hepatocarcinoma, including surgical resection, liver transplantation, TACE, local ablative therapies and even as monotherapy for middle-advanced stage hepatocarcinoma. Clinical practices have confirmed that TCM is effective to alleviate clinical symptoms, improve quality of life and immune function, prevent recurrence and metastasis, delay tumor progression, and prolong survival time in hepatocarcinoma patients. The effective mechanism of TCM against hepatocarcinoma is related to inducing apoptosis, autophagy, anoikis and cell senescence, arresting cell cycle, regulating immune function, inhibiting metastasis and angiogenesis, reversing drug resistance and enhancing effects of chemotherapy. Along with the progress of research in this field, TCM will contribute more to the prevention and treatment of hepatocarcinoma.

Research Status of Serum Pharmacology and Serum Pharmacochemistry of Traditional Chinese Medicine

Serum pharmacochemistry of traditional Chinese medicine has become a more accurate and rapidly developing reasonable way to analyze the effective material basis of traditional Chinese medicine in recent years. Through this method, we can select very complex Chinese medicine components and clarify the effective substances consistent with the main functions, and then separate and purify effective ingredients in traditional Chinese medicine, so as to explain the material basis of the drug effect and prove the rationality and principle of action of Chinese medicine compounds. It can show the multi-component and multi-target characteristic of traditional Chinese medicine, and after analyzing the migrating components of serum, we can explore the direct effective substances that act on the patient’s body, so as to accelerate and accurately complete the in-depth study of the effective substances of Chinese medicine.

Clinical evidence of three traditional Chinese medicine drugs and three herbal formulas for COVID-19:A systematic review and meta-analysis of the Chinese population

Background The coronavirus disease 2019(COVID-19)continues to spread worldwide.Integrated Chinese and Western medicine have had some successes in treating COVID-19.Objective This study aims to evaluate the efficacy and safety of three traditional Chinese medicine drugs and three herbal formulas(3-drugs-3-formulas)in patients with COVID-19.Search strategy Relevant studies were identified from 12 electronic databases searched from their establishment to April 7,2022.Inclusion criteria Randomized controlled trials(RCTs),non-RCTs and cohort studies that evaluated the effects of 3-drugs-3-formulas for COVID-19.The treatment group was treated with one of the 3-drugs-3-formulas plus conventional treatment.The control group was treated with conventional treatment.Data extraction and analysis Two evaluators screened and selected literature independently,then extracted basic information and assessed risk of bias.The treatment outcome measures were duration of main symptoms,hospitalization time,aggravation rate and mortality.RevMan 5.4 was used to analyze the pooled results reported as mean difference(MD)with 95%confidence interval(CI)for continuous data and risk ratio(RR)with 95%CI for dichotomous data.Results Forty-one studies with a total of 13,260 participants were identified.Our analysis suggests that compared with conventional treatment,the combination of 3-drugs-3-formulas might shorten duration of fever(MD=–1.39;95%CI:–2.19 to–0.59;P<0.05),cough(MD=–1.57;95%CI:–2.16 to–0.98;P<0.05)and fatigue(MD=–1.36;95%CI:–2.21 to–0.51;P<0.05),decrease length of hospital stay(MD=–2.62;95%CI–3.52 to–1.72;P<0.05),the time for nucleic acid conversion(MD=–2.92;95%CI:–4.26 to–1.59;P<0.05),aggravation rate(RR=0.49;95%CI:0.38 to 0.64;P<0.05)and mortality(RR=0.34;95%CI:0.19 to 0.62;P<0.05),and increase the recovery rate of chest computerized tomography manifestations(RR=1.22;95%CI:1.14 to 1.3;P<0.05)and total effectiveness(RR=1.24;95%CI:1.09 to 1.42;P<0.05).Conclusion The 3-drugs-3-formulas can play an active role in treating all stages of COVID-19.No severe adverse events related to 3-drugs-3-formulas were observed.Hence,3-drugs-3-formulas combined with conventional therapies have effective therapeutic value for COVID-19 patients.Further long-term high-quality studies are essential to demonstrate the clinical benefits of each formula.

益气小复方通过下调lncRNA HCP5表达增强三阴性乳腺癌顺铂耐药细胞株MDA-MB-231/DDP对顺铂敏感性的机制研究

目的探讨益气小复方增强三阴性乳腺癌顺铂耐药细胞株MDA-MB-231/DDP顺铂敏感性的可能机制。方法以不同浓度的顺铂(0、2、4、8、16、32、64 mg/L)分别作用于MDA-MB-231野生、耐药细胞株24 h,噻唑蓝(MTT)比色法检测细胞增殖,鉴定耐药细胞株的顺铂耐药性。上述梯度浓度的顺铂及顺铂加固定浓度(5mg/L)益气小复方分别作用于野生、耐药细胞株及长链非编码RNA人源组织相容性白细胞抗原复合物P5(LncRNAHCP5)基因过表达、敲减的野生、耐药细胞株,MTT比色法检测细胞增殖,流式细胞仪检测细胞凋亡,实时荧光定量逆转录聚合酶链式反应(RT-qPCR)法检测HCP5mRNA表达水平,蛋白质免疫印迹(Western blot)法检测磷酸酶张力蛋白同源物(PTEN)、磷酸化蛋白激酶B(p-Akt)蛋白表达水平。结果MDA-MB-231耐药细胞株较野生细胞株顺铂耐药指数为42.4。益气小复方同顺铂联用较单独使用顺铂,对耐药细胞株的增殖抑制率及诱导细胞凋亡比率均有提高(P<0.05)。MDA-MB-231耐药细胞株较野生细胞株,lncRNAHCP5、p-Akt蛋白表达升高,PTEN蛋白表达降低(P<0.05);益气小复方可降低MDA-MB-231耐药细胞株lncRNA HCP5、p-Akt蛋白表达,提高PTEN蛋白表达(P<0.05)。结论益气小复方可能通过下调lncRNAHCP5表达而升高PTEN蛋白表达、降低p-Akt蛋白表达,进而增强MDA-MB-231耐药细胞株对顺铂的敏感性。

中医药治疗卵巢癌的机制研究进展

卵巢癌具有难检测、难治疗、复发率高等临床特点,是致死率最高的妇科恶性肿瘤之一。早期症状隐匿,发现时多已进展至晚期,手术后铂类药物化疗是目前的主要治疗手段,但长期使用会产生耐药性,且不良反应极多。近年来,随着中医学的不断进步和发展,中药已成为目前抗卵巢癌研究的热点。笔者在国内外数据库中检索相关研究论文,发现中药具有抑制卵巢癌细胞增殖、促进细胞凋亡、逆转耐药性等作用机制,主要作用在PI3K/Akt/mTOR、Wnt/β-catenin、Notch、NF-κB、MAPK信号通路。

菌酶协同发酵复方中草药对断奶仔猪生长性能及血清免疫、抗氧化和生长相关激素指标的影响

本试验旨在研究饲粮中添加菌酶协同发酵复方中草药对断奶仔猪生长性能及血清免疫、抗氧化和生长相关激素指标的影响,为复方中草药在断奶仔猪生产上的应用提供理论依据。试验采用单因素随机化设计,选用健康、体重相近的(28±2)日龄断奶仔猪160头,随机分为4个组,每组5个重复,每个重复8头猪(公母各占1/2)。对照组饲喂基础饲粮,试验组分别在基础饲粮中添加0.5%、1.0%、2.0%的菌酶协同发酵复方中草药。试验期为28 d。结果表明:1)与对照组相比,0.5%、1.0%和2.0%菌酶协同发酵复方中草药组的平均日增重显著升高(P<0.05),平均日采食量和料重比显著降低(P<0.05)。2)与对照组相比,0.5%、1.0%和2.0%菌酶协同发酵复方中草药组的血清免疫球蛋白A(IgA)和免疫球蛋白M(IgM)含量显著升高(P<0.05),血清白细胞介素-6(IL-6)含量显著降低(P<0.05);1.0%菌酶协同发酵复方中草药组的血清免疫球蛋白G(IgG)、白蛋白(ALB)和总蛋白(TP)含量显著升高(P<0.05),血清白细胞介素-1(IL-1)含量显著降低(P<0.05)。3)与对照组相比,1.0%和2.0%菌酶协同发酵复方中草药组的血清总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)活性和还原型谷胱甘肽(GSH)含量显著升高(P<0.05),1.0%菌酶协同发酵复方中草药组的血清丙二醛(MDA)含量显著降低(P<0.05)。4)与对照组相比,0.5%、1.0%和2.0%菌酶协同发酵复方中草药组的血清生长激素(GH)和胃泌素(GAS)含量显著升高(P<0.05),血清皮质醇(COR)含量显著降低(P<0.05);1.0%菌酶协同发酵复方中草药组的血清胰岛素生长因子-1(IGF-1)、三碘甲状腺原氨酸(T 3)和四碘甲状腺原氨酸(T 4)含量显著升高(P<0.05)。由此可见,饲粮中添加菌酶协同发酵复方中草药能够提高断奶仔猪生长性能,增强机体免疫功能和抗氧化能力,提高血清生长相关激素含量。本试验条件下,饲粮中菌酶协同发酵复方中草药适宜添加水平为1.0%。

温经汤对大鼠子宫内膜异位症SPARC介导的上皮-间质转化的影响

目的探讨温经汤对子宫内膜异位症(EMT)大鼠模型富含半胱氨酸的酸性分泌蛋白(SPARC)介导的上皮-间质转化的影响。方法采用手术自体移植子宫内膜块法建立EMT大鼠模型,将建模成功的40只大鼠随机分为模型组(给予质量分数为0.9%的氯化钠溶液10 mL/kg)、孕三烯酮组(给予孕三烯酮溶液0.5 mg/kg)以及温经汤低、中、高剂量组(分别给予温经汤免煎颗粒剂8.19 g/kg、16.38 g/kg、32.76 g/kg),每组各8只,另取7只未手术大鼠作为正常对照组(给予质量分数为0.9%的氯化钠溶液10 mL/kg)。所有大鼠均连续灌胃给药3周后进行取材。腹主动脉取血,采用酶联免疫吸附试验(ELISA)法检测血清中SPARC水平。电子游标卡尺测量异位病灶体积,计算生长抑制率。取下异位病灶组织(正常对照组取下双侧子宫组织)采用免疫组织化学法检测内膜组织中SPARC、锌指转录因子(Snail)、E-钙黏蛋白(E-cadherin)和波形蛋白(Vimentin)的表达,采用Western blot法和RT-qPCR法测定内膜组织中上述因子的蛋白和mRNA相对表达量。结果各治疗组异位病灶的生长抑制率与模型组比较差异均有统计学意义(P<0.05)。与正常对照组比较,模型组血清中SPARC水平显著升高(P<0.05),各治疗组血清中SPARC水平均明显低于模型组(P<0.05)。模型组异位内膜中SPARC、Snail、Vimentin呈高表达,E-cadherin呈低表达,经温经汤治疗后,异位内膜中SPARC、Snail、Vimentin的阳性表达减少,E-cadherin的阳性表达增加。温经汤中、高剂量组和孕三烯酮组异位内膜中SPARC、Snail、Vimentin的蛋白相对表达量均明显低于模型组(P<0.05),E-cadherin的蛋白相对表达量显著高于模型组(P<0.05)。温经汤高剂量组和孕三烯酮组异位内膜中Snail、Vimentin mRNA相对表达量均较模型组显著降低(P<0.05),E-cadherin mRNA相对表达量明显高于模型组(P<0.05)。结论温经汤可以降低EMT大鼠模型血清中SPARC水平,下调异位内膜中SPARC、Snail、Vimentin蛋白和mRNA表达,升高异位内膜中E-cadherin蛋白和mRNA表达,通过调控SPARC介导的上皮-间质转化,从而抑制异位内膜病灶的生长。

益神宁心方对斑马鱼睡眠剥夺模型行为学及神经递质的影响

目的观察益神宁心方对斑马鱼睡眠剥夺模型行为的影响,并对其机制进行初步探索。方法将受精后5 d(5 dpf)野生型AB系斑马鱼随机分为正常组、模型组(咖啡因300μmol/L)、褪黑素组(10μmol/L)、益神宁心方低剂量组(100 mg/L)、益神宁心方中剂量组(300 mg/L)和益神宁心方高剂量组(900 mg/L),咖啡因诱导建立斑马鱼睡眠剥夺模型。应用行为追踪系统定量监测自主活动1 h,明暗交替下连续测定斑马鱼的趋触性行为15 min,酶联免疫吸附试验(ELISA)法检测γ-氨基丁酸(GABA)、5-羟色胺(5-HT)和褪黑素(MT)的含量,实时荧光定量逆转录聚合酶链式反应(RT-qPCR)法检测斑马鱼组织GABA A型受体a1亚单位基因(gabra1)、γ2亚单位基因(gabrg2)和5-HT受体1A类亚型基因(htr1aa)、1D类亚型基因(htr1bd)及MT受体1A类亚型基因(mtnr1aa)、1B类亚型基因(mtnr1ba)mRNA相对表达量。结果与正常组比较,模型组斑马鱼运动状态覆盖距离、运动状态持续时间及中运动时间均显著增加(P<0.05),静止状态持续时间显著减少(P<0.05);中心区域时间百分比及中心区域距离百分比均显著减少(P<0.05);GABA、MT含量及gabra1、gabrg2、mtnr1aa、mtnr1ba mRNA相对表达量均显著降低(P<0.05),5-HT含量及htr1aa、htr1bd mRNA相对表达量均显著升高(P<0.05)。与模型组比较,益神宁心方高、中剂量组运动距离、运动时间、中运动时间减少(P<0.05),静息时间增加(P<0.05);益神宁心方高剂量组中心区域时间百分比及中心区域距离百分比增加(P<0.05);益神宁心方高剂量组GABA、MT含量和gabra1、mtnr1aa、mtnr1ba mRNA相对表达量升高(P<0.05),5-HT含量和htr1aa mRNA相对表达量降低(P<0.05);益神宁心方中剂量组gabrg2、mtnr1ba mRNA相对表达量升高,5-HT含量和htr1bd mRNA相对表达量降低(P<0.05)。结论益神宁心方可以改善咖啡因造模斑马鱼的睡眠剥夺状态,改善焦虑行为,其机制可能与调节GABA、5-HT、MT相关紊乱的基因水平相关。

越婢汤含药血清对阿霉素损伤的人脐静脉血管内皮细胞的干预作用

目的基于小窝蛋白-1(Cav-1)/内皮型一氧化氮合酶(eNOS)通路,探讨越婢汤含药血清对阿霉素(ADR)损伤的人脐静脉血管内皮细胞(HUVEC)模型的作用机制。方法制备越婢汤含药血清及空白血清,体外培养HUVEC,采用ADR诱导建立HUVEC损伤模型,将细胞分为对照组、模型组、越婢汤组(2.5%、5%、10%、20%含药血清),给予相应药物处理24 h。细胞增殖-毒性检测(CCK-8)法检测细胞存活率,划痕实验检测细胞迁移能力,Western blot法检测Cav-1/eNOS信号通路相关蛋白表达,免疫荧光法检测细胞Cav-1表达水平,酶联免疫吸附测定(ELISA)法检测细胞上清液Cav-1的含量。结果与对照组比较,模型组细胞增殖及迁移能力降低(P<0.05),细胞内Cav-1、磷酸化内皮型一氧化氮合酶(p-eNOS)、血管内皮细胞钙黏蛋白(VE-cadherin)表达下降(P<0.05),细胞上清液Cav-1含量上升(P<0.05)。与对照组比较,各浓度越婢汤含药血清对HUVEC细胞活力无明显影响(P>0.05)。与模型组比较,越婢汤各组能促进细胞迁移(P<0.05);2.5%浓度的含药血清对细胞Cav-1等蛋白表达无影响(P>0.05);5%、10%、20%浓度含药血清能增加细胞内Cav-1、p-eNOS、VE-cadherin蛋白的表达(P<0.05),下调细胞上清液Cav-1的含量(P<0.05)。结论越婢汤含药血清可以降低ADR对HUVEC细胞的损伤,促进HUVEC细胞的增殖、迁移,其保护作用可能与调控Cav-1/eNOS信号通路有关。

复方中草药制剂对林下绿壳蛋乌鸡产蛋性能、蛋品质和血清生化指标的影响

本研究旨在探究日粮中添加不同水平的复方中草药制剂对林下绿壳蛋乌鸡产蛋性能、蛋品质、血清生化指标的影响。选取520日龄健康、体质量接近的绿壳蛋乌鸡560羽,随机分成4组,分别为对照组和试验Ⅰ组、Ⅱ组、Ⅲ组。对照组饲喂基础日粮,试验Ⅰ组、Ⅱ组、Ⅲ组分别在基础日粮中添加0.5%、1.0%、1.5%的复方中草药制剂,试验期45 d。结果显示,日粮中添加不同水平的复方中草药制剂对林下绿壳蛋乌鸡的平均蛋重、平均产蛋率、绿壳蛋破损率有显著影响,其中Ⅱ组平均蛋重显著高于对照组(P<0.05),Ⅰ组、Ⅱ组平均产蛋率显著高于对照组(P<0.05),Ⅱ组绿壳蛋破损率显著低于对照组(P<0.05);日粮中添加不同水平的复方中草药制剂对绿壳蛋蛋黄相对重、蛋白高度、蛋黄水分含量、蛋黄指数及哈氏单位有显著影响,其中Ⅱ组绿壳蛋蛋黄相对重显著高于对照组(P<0.05),Ⅰ组、Ⅱ组、Ⅲ组绿壳蛋蛋白高度显著高于对照组(P<0.05),Ⅱ组、Ⅲ组绿壳蛋水分含量显著低于对照组和Ⅰ组(P<0.05),Ⅱ组绿壳蛋蛋黄指数显著高于对照组、Ⅰ组、Ⅲ组(P<0.05),Ⅱ组绿壳蛋哈氏单位显著高于对照组和Ⅲ组(P<0.05);日粮中添加不同水平的复方中草药制剂对林下绿壳蛋乌鸡的血清总蛋白(TP)、球蛋白(GLO)、丙氨酸氨基转移酶(ALT)、胆固醇(TC)和甘油三酯(TG)有显著影响,其中Ⅰ组、Ⅱ组血清TP含量显著高于对照组(P<0.05),Ⅰ组、Ⅱ组、Ⅲ组血清GLO含量显著高于对照组(P<0.05),Ⅲ组血清ALT活性显著高于对照组和Ⅰ组(P<0.05),Ⅱ组血清TC和TG含量显著高于对照组(P<0.05)。综上,日粮中添加不同水平的复方中草药制剂能改善绿壳蛋乌鸡的产蛋性能、蛋品质及血清生化指标,且以1.0%添加量的复方中草药制剂效果最佳。

橘皮竹茹汤对化疗性异食癖大鼠模型5-羟色胺3受体蛋白和mRNA表达的影响

目的观察橘皮竹茹汤对化疗性异食癖大鼠模型止呕作用及对5-羟色胺3受体(5-HT3R)蛋白和mRNA的影响。方法将36只Wistar雄性大鼠随机分为正常对照组、中药对照组(橘皮竹茹汤10.6 g/kg,不造模)、模型组、昂丹司琼组(2.6 mg/kg)、橘皮竹茹汤低剂量组(5.3 g/kg)和橘皮竹茹汤高剂量组(10.6 g/kg),每组6只。各组大鼠给予相应干预措施6 d(每日2次)后,采用腹腔注射顺铂(6 mg/kg)的方式诱导建立化疗性异食癖大鼠模型,观察并记录造模后24 h内大鼠体质量、摄食量和高岭土摄入量的变化。继续干预1 d后,苏木精-伊红(HE)染色观察各组大鼠胃窦、回肠组织形态学变化;实时荧光定量逆转录聚合酶链式反应(RT-qPCR)法检测延髓、回肠组织中5-HT3R、色氨酸羟化酶(TPH)、单胺氧化酶A(MAOA)mRNA表达;Western blot法检测延髓组织中5-HT3R蛋白的表达。结果①与正常对照组比较,模型组大鼠体质量、摄食量降低(P<0.05),高岭土摄入量显著增加(P<0.05);与模型组比较,昂丹司琼组和橘皮竹茹汤低、高剂量组大鼠高岭土摄入量显著降低(P<0.05)。②HE染色显示,与正常对照组比较,模型组胃窦组织上皮细胞受损,固有层腺体排列疏松、紊乱,回肠上皮部分缺失,腺体排列紊乱;与模型组比较,昂丹司琼组和橘皮竹茹汤低、高剂组胃窦和回肠组织病理改变减轻。③RT-qPCR结果显示,与正常对照组比较,模型组大鼠延髓、回肠5-HT3R mRNA表达水平显著升高(P<0.05),回肠MAOA mRNA表达水平显著降低(P<0.05);与模型组比较,橘皮竹茹汤高剂量组大鼠延髓5-HT3R mRNA表达水平明显降低(P<0.05),橘皮竹茹汤低剂量组回肠TPH1 mRNA、橘皮竹茹汤高剂量组延髓TPH2 mRNA表达水平明显降低(P<0.05),昂丹司琼组、橘皮竹茹汤低剂量组、橘皮竹茹汤高剂量组回肠MAOA mRNA表达水平明显升高(P<0.05)。④Western blot结果显示,与正常对照组比较,模型组大鼠延髓5⁃HT3R蛋白表达水平显著升高(P<0.05);与模型组比较,橘皮竹茹汤高剂量组大鼠延髓5-HT3R蛋白表达水平显著降低(P<0.05)。结论橘皮竹茹汤可以通过抑制延髓5-HT3R蛋白和mRNA的表达,调控5-羟色胺合成与代谢相关酶,进而改善化疗导致的恶心呕吐。