Seismic control of multi-degrees-of-freedom structures by vertical mass isolation method using MR dampers

Vertical mass isolation(VMI)is one of the novel methods for the seismic control of structures.In this method,the entire structure is assumed to consist of two mass and stiffness subsystems,and an isolated layer is located among them.In this study,the magnetorheological damper in three modes:passive-off,passive-on,and semi-active mode with variable voltage between zero and 9 volts was used as an isolated layer between two subsystems.Multi-degrees-of-freedom structures with 5,10,and 15 floors in two dimensions were examined under 11 pairs of near field earthquakes.On each level,the displacement of MR dampers was taken into account.The responses of maximum displacement,maximum inter-story drift,and maximum base shear in controlled and uncontrolled buildings were compared to assess the suggested approach for seismic control of the structures.According to the results,the semi-active control method can reduce the response by more than 12%compared to the uncontrolled mode in terms of maximum displacement of the mass subsystem of the structures.This method can reduce more than 16%and 20%of the responses compared to the uncontrolled mode in terms of maximum inter-story drift and base shear of the structure,respectively.

Near resonance vibration isolation on a levered-dual response(LEDAR)Coulomb-damped system by differential preloads/offsets in linear springs

The levered-dual response(LEDAR)Coulomb-damped system attains near resonant vibration isolation by differential preloads/offsets in linear springs.It takes the advantages of both the preloads/offsets in linear springs and the guiderail friction for realizing different levels of vibration isolation.The isolation capacities are investigated on the strategies with both the horizontal and vertical guiderails,with the horizontal rail only,and without guiderails.The compressive preloads generally result in the consumption of most of the initial excitation energy so as to overcome the potential threshold.The isolation onsets at the frequency ratio of 1∓0.095 on the left-hand side(LHS)and the right-hand side(RHS)of the lever are relative to the load plate connector.The observed near resonant isolation thus makes the LEDAR system a candidate for the isolation of the mechanical systems about resonance while opening a path for simultaneous harvesterisolation functions and passive functions at extreme frequencies.

Dynamic analysis of a novel multilink-spring mechanism for vibration isolation and energy harvesting

Due to technical limitations,existing vibration isolation and energy harvesting(VIEH)devices have poor performance at low frequency.This paper proposes a new multilink-spring mechanism(MLSM)that can be used to solve this problem.The VIEH performance of the MLSM under harmonic excitation and Gaussian white noise was analyzed.It was found that the MLSM has good vibration isolation performance for low-frequency isolation and the frequency band can be widened by adjusting parameters to achieve a higher energy harvesting power.By comparison with two special cases,the results show that the MLSM is basically the same as the other two oscillators in terms of vibration isolation but has better energy harvesting performance under multistable characteristics.The MLSM is expected to reduce the impact of vibration on high-precision sensitive equipment in some special sites such as subways and mines,and at the same time supply power to structural health monitoring devices.

Prediction of Damping Capacity Demand in Seismic Base Isolators via Machine Learning

Base isolators used in buildings provide both a good acceleration reduction and structural vibration control structures.The base isolators may lose their damping capacity over time due to environmental or dynamic effects.This deterioration of them requires the determination of the maintenance and repair needs and is important for the long-termisolator life.In this study,an artificial intelligence prediction model has been developed to determine the damage and maintenance-repair requirements of isolators as a result of environmental effects and dynamic factors over time.With the developed model,the required damping capacity of the isolator structure was estimated and compared with the previously placed isolator capacity,and the decrease in the damping property was tried to be determined.For this purpose,a data set was created by collecting the behavior of structures with single degrees of freedom(SDOF),different stiffness,damping ratio and natural period isolated from the foundation under far fault earthquakes.The data is divided into 5 different damping classes varying between 10%and 50%.Machine learning model was trained in damping classes with the data on the structure’s response to random seismic vibrations.As a result of the isolator behavior under randomly selected earthquakes,the recorded motion and structural acceleration of the structure against any seismic vibration were examined,and the decrease in the damping capacity was estimated on a class basis.The performance loss of the isolators,which are separated according to their damping properties,has been tried to be determined,and the reductions in the amounts to be taken into account have been determined by class.In the developed prediction model,using various supervised machine learning classification algorithms,the classification algorithm providing the highest precision for the model has been decided.When the results are examined,it has been determined that the damping of the isolator structure with the machine learning method is predicted successfully at a level exceeding 96%,and it is an effective method in deciding whether there is a decrease in the damping capacity.

Impact of surface-reflected seismic waves on the seismic isolation performance of circular tunnel isolation layers

Seismic isolation is an effective strategy to mitigate the risk of seismic damage in tunnels.However,the impact of surface-reflected seismic waves on the effectiveness of tunnel isolation layers remains under explored.In this study,we employ the wave function expansion method to provide analytical solutions for the dynamic responses of linings in an elastic half-space and an infinite elastic space.By comparing the results of the two models,we investigate the seismic isolation effect of tunnel isolation layers induced by reflected seismic waves.Our findings reveal significant differences in the dynamic responses of the lining in the elastic half-space and the infinitely elastic space.Specifically,the dynamic stress concentration factor(DSCF)of the lining in the elastic half-space exhibits periodic fluctuations,influenced by the incident wave frequency and tunnel depth,while the DSCF in the infinitely elastic space remain stable.Overall,the seismic isolation application of the tunnel isolation layer is found to be less affected by surface-reflected seismic waves.Our results provide valuable insights for the design and assessment of the seismic isolation effect of tunnel isolation layers.

No-touch isolation technique in emergency pancreaticoduodenectomy for neoplastic hemorrhage: Two case reports and review of literature

BACKGROUND Emergency pancreaticoduodenectomy(EPD)is a rare event for complex periam-pullary etiology.Increased intraoperative blood loss is correlated with poor post-operative outcomes.CASE SUMMARY Two patients underwent EPD using a no-touch isolation technique,in which all arteries supplying the pancreatic head region were ligated and divided before manipulation of the pancreatic head and duodenum.The operative times were 220 and 239 min,and the blood loss was 70 and 270 g,respectively.The patients were discharged on the 14^(th) and 10^(th) postoperative day,respectively.Thirty-two patients underwent EPD for the treatment of neoplastic bleeding.The mean operative time was 361.6 min,and the mean blood loss was 747.3 g.The comp-lication rate was 37.5%.The in-hospital mortality rate was 9.38%.CONCLUSION The no-touch isolation technique is feasible,safe,and effective for reducing intraoperative blood loss in EPD.

Actuator and sensor fault isolation in a class of nonlinear dynamical systems

Fault isolation in dynamical systems is a challenging task due to modeling uncertainty and measurement noise,interactive effects of multiple faults and fault propagation.This paper proposes a unified approach for isolation of multiple actuator or sensor faults in a class of nonlinear uncertain dynamical systems.Actuator and sensor fault isolation are accomplished in two independent modules,that monitor the system and are able to isolate the potential faulty actuator(s)or sensor(s).For the sensor fault isolation(SFI)case,a module is designed which monitors the system and utilizes an adaptive isolation threshold on the output residuals computed via a nonlinear estimation scheme that allows the isolation of single/multiple faulty sensor(s).For the actuator fault isolation(AFI)case,a second module is designed,which utilizes a learning-based scheme for adaptive approximation of faulty actuator(s)and,based on a reasoning decision logic and suitably designed AFI thresholds,the faulty actuator(s)set can be determined.The effectiveness of the proposed fault isolation approach developed in this paper is demonstrated through a simulation example.

Optimization of Cellulose Nanocrystal Isolation from Ayous Sawdust Using Response Surface Methodology

This study focuses on the extraction of cellulose nanocrystals (CNC), from microcrystalline cellulose (MCC), derived from Ayous sawdust. The process involves multiple steps and a large amount of chemical products. The objective of this research was to determine the effects of factors that impact the isolation process and to identify the optimal conditions for CNC isolation by using the response surface methodology. The factors that varied during the process were the quantity of MCC, the concentration of sulfuric acid, the hydrolysis time and temperature, and the ultrasonic treatment time. The response measured was the yield. The study found that with 5.80 g of microcrystalline cellulose, a sulfuric acid concentration of 63.50% (w/w), a hydrolysis time of 53 minutes, a hydrolysis temperature of 69˚C, and a sonication time of 19 minutes are the ideal conditions for isolation. The experimental yield achieved was (37.84 ± 0.99) %. The main factors influencing the process were the sulfuric acid concentration, hydrolysis time and temperature, with a significant influence (p < 0.05). Infrared characterization results showed that nanocrystals were indeed isolated. With a crystallinity of 35.23 and 79.74, respectively, for Ayous wood fiber and nanocrystalline cellulose were observed by X-ray diffraction, with the formation of type II cellulose, thermodynamically more stable than native cellulose type I.

Non-enzymatic methods for isolation of stromal vascular fraction and adipose-derived stem cells:A systematic review

BACKGROUND Adipose-derived stem cells(ADSCs)and the stromal vascular fraction(SVF)have garnered substantial interest in regenerative medicine due to their potential to treat a wide range of conditions.Traditional enzymatic methods for isolating these cells face challenges such as high costs,lengthy processing time,and regulatory complexities.AIM This systematic review aimed to assess the efficacy and practicality of nonenzymatic,mechanical methods for isolating SVF and ADSCs,comparing these to conventional enzymatic approaches.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,a comprehensive literature search was conducted across multiple databases.Studies were selected based on inclusion criteria focused on non-enzymatic isolation methods for SVF and ADSCs from adipose tissue.The risk of bias was assessed,and a qualitative synthesis of findings was performed due to the methodological heterogeneity of the included studies.RESULTS Nineteen studies met the inclusion criteria,highlighting various mechanical techniques such as centrifugation,vortexing,and ultrasonic cavitation.The review identified significant variability in cell yield and viability,and the integrity of isolated cells across different non-enzymatic methods compared to enzymatic procedures.Despite some advantages of mechanical methods,including reduced processing time and avoidance of enzymatic reagents,the evidence suggests a need for optimization to match the cell quality and therapeutic efficacy achievable with enzymatic isolation.CONCLUSION Non-enzymatic,mechanical methods offer a promising alternative to enzymatic isolation of SVF and ADSCs,potentially simplifying the isolation process and reducing regulatory hurdles.However,further research is necessary to standardize these techniques and ensure consistent,high-quality cell yields for clinical applications.The development of efficient,safe,and reproducible non-enzymatic isolation methods could significantly advance the field of regenerative medicine.

Seismic Response Analysis of Steel Structure Isolation System Under Long-Period Seismic Motion

To analyze the seismic response of steel structure isolation systems under long-period seismic motion,a 9-story steel frame building was selected as the subject.Five steel structure finite element models were established using SAP2000.Response spectrum analysis was conducted on the seismic motion to determine if it adhered to the characteristics of long-period seismic motion.Modal analysis of each structural model revealed that the isolation structure significantly prolonged the structural natural vibration period and enhanced seismic performance.Base reactions and floor displacements of various structures notably increased under long-period seismic motion compared to regular seismic activity.Placing isolation bearings in the lower part of the structure proved more effective under long-period seismic motion.In seismic design engineering,it is essential to consider the impact of long-period seismic motion on structures and the potential failure of isolation bearings.

Analysis of the Current Situation and Influencing Factors of Social Isolation Among the Elderly in the Community

Objective: To investigate the current situation of social isolation among the elderly in the community, and to analyze its influencing factors. Methods: A total of 265 elderly people were selected to conduct the survey using the general information questionnaire and the Chinese version of the social isolation scale for the elderly. Results: The social isolation score of the elderly was (20.15 ± 0.23). Factors such as age, education level, economic status, and social participation ability influenced the social isolation score (P < 0.05). Conclusion: The social isolation of the elderly is more serious, and the social isolation can be alleviated by improving the level of education and the economic situation and strengthening social participation.

Seismic Reduction and Isolation Design Strategies for Bridges in High-Intensity Earthquake Areas

High-intensity earthquakes can cause severe damage to bridges,buildings,and ground surfaces,as well as disrupt human activities.Such earthquakes can create long-distance,high-intensity surface movements that negatively impact bridge structures.This article delves into the seismic reduction and isolation design strategies for bridges in high-intensity earthquake areas.It analyzes various seismic reduction and isolation technologies and provides case studies to help relevant units understand the design strategies of these technologies.The results of this article can be used as a guideline to effectively enhance the seismic performance of bridges in high-intensity earthquake areas.

Validation of the Portuguese version of the social isolation scale with a sample of community-dwelling older adults

Objectives The aim of this study was to analyze the psychometric properties(reliability and validity)of the Social Isolation Scale(SIS)in a sample of Portuguese community-dwelling older adults.Methods A transversal descriptive study was carried out with a convenience sample of 250 community-dwelling older adults(≥65 years).The survey comprised a sociodemographic questionnaire,SIS,Geriatric Depression Scale-4(GDS-4),6-item Lubben Social Network Scale(LSNS-6),a loneliness self-assessment question,and Satisfaction with Life Scale(SWLS).Construct validity(confirmatory factor analysis)and convergent validity were analyzed,and ISI internal reliability(composite reliability),external reliability(test-retest,intraclass correlation coefficient)and inter-rater reliability(Cohen’s kappa coefficient)were evaluated.Results Confirmatory factor analysis showed a two-factor model with an excellent index of fit.The SIS showed significant correlations with LSNS-6(rs=0.47),SWLS(rs=0.26),the loneliness self-assessment question(rs=0.35),and GDS-4(rs=−0.16).SIS composite reliability was good(0.708).The inter-class correlation coefficient varied from 0.84 to 0.98.The Cohen’s kappa coefficient ranged from 0.936 to 1.Conclusions SIS has been shown to be a valid and reliable instrument for assessing social isolation among Portuguese community-dwelling older adults.Healthcare professionals,particularly nurses working in community settings,can use SIS to assess social isolation in older adults to design,implement,and evaluate interventions.

人参皂苷Rc通过调控AMPK通路介导的细胞焦亡减轻小鼠脑缺血再灌注损伤

目的:探讨人参皂苷Rc对脑缺血再灌注损伤(CIRI)小鼠的保护作用,并从细胞焦亡角度阐释其作用机制。方法:将C57BL/6小鼠随机分为假手术(sham)组、大脑中动脉闭塞/再灌注(MCAO/R)组、人参皂苷Rc+MCAO/R组(Rc组)、AMP活化蛋白激酶(AMPK)激动剂阿卡地新(AICAR)+MCAO/R组(agonist组)和人参皂苷Rc+MCAO/R+AMPK抑制剂Compound C组(Rc+inhibitor组)。对agonist组小鼠给予AICAR(500 mg/kg)腹腔注射,Rc+inhibitor组小鼠给予Compound C(20 mg/kg)腹腔注射;Rc组和Rc+inhibitor组小鼠造模后给予人参皂苷Rc(40 mg/kg)灌胃,每天一次,连续7 d;sham组和MCAO/R组则给予等体积的纯化水。Zea Longa评分观察小鼠神经功能缺损程度,TTC染色观察小鼠脑梗死体积,干湿重法观察小鼠脑水肿程度,HE染色观察小鼠脑组织病理形态的改变,RT-qPCR和Western blot检测小鼠脑组织AMPK、核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、胱天蛋白酶1(caspase-1)和焦亡效应蛋白消皮素D(GSDMD)的表达,ELISA检测炎症因子白细胞介素1β(IL-1β)和IL-18的含量。结果:Rc组和agonist组小鼠神经功能缺损症状减轻,脑梗死体积减小,脑水肿和神经元病理损伤受到抑制,脑组织pAMPK/AMPK比值和AMPK mRNA表达水平升高,细胞焦亡相关蛋白NLRP3、caspase-1和GSDMD的mRNA和蛋白表达水平降低,炎症因子IL-1β和IL-18表达水平降低。Rc+inhibitor组小鼠脑组织p-AMPK/AMPK比值和AMPK mRNA表达水平较Rc组显著下降(P<0.05),NLRP3、caspase-1和GSDMD的mRNA和蛋白表达水平,以及IL-1β和IL-18表达水平显著升高(P<0.05),小鼠神经功能缺损程度评分升高,脑梗死体积增大,脑水肿和神经元病理损伤显著加重(P<0.05)。结论:人参皂苷Rc可能通过活化AMPK通路抑制NLRP3/caspase-1/GSDMD介导的细胞焦亡,从而减轻小鼠CIRI。

基于NOD2介导的AMPK/mTOR信号通路探讨宫颈癌细胞恶性行为的机制

目的 基于核苷酸结合寡聚化结构域受体2(NOD2)介导的AMP活化蛋白激酶(AMPK)/雷帕霉素靶蛋白(mTOR)信号通路探讨宫颈癌(CC)细胞恶性行为的机制。方法 生物信息学分析确定NOD2在CC组织中的表达。将靶向NOD2(shNOD2)、shRNAs阴性对照(shNC)以及NOD2过表达(NOD2)质粒和载体(Vec)转染CC细胞。通过CCK-8测定、集落形成和Transwell细胞侵袭测定来确定NOD2对CC细胞生长的影响。通过高通量RNA测序(RNA-Seq)进行转录组分析。Western blot试验检测细胞系中NOD2、AMPK/mTOR信号通路和自噬蛋白的表达。24只雌性BALB/c裸鼠随机分为4组,每组6只:载体组(Vec组)、NOD2过表达组(NOD2组)、shNC组和shNOD2组。构建小鼠远处转移模型,监测肺转移的荧光强度,计数肺转移结节的数量。结果 在线数据库分析显示,NOD2在CC组织中表达明显高于正常组织,并且不同分期的CC中NOD2的mRNA表达差异有统计学意义(P<0.05)。此外,NOD2的高表达与较差的总生存期和无病生存期相关(P<0.05)。NOD2过表达对CC细胞增殖、集落形成、迁移和侵袭具有促进作用,而NOD2敲低则相反。与体外结果一致,在转移的小鼠尾静脉注射模型中,NOD2组CC细胞的肺定殖、肺转移灶较Vec组增加(P<0.05),而shNOD2组CC细胞的肺定殖、肺转移灶较shNC组减少(P<0.05)。RNA-Seq结果显示NOD2表达与AMPK信号激活、mTOR信号抑制、自噬调节途径激活和自噬体形成显著相关。与shNC组相比,shNOD2组磷酸化AMPK、LC3蛋白表达水平减少(P<0.05),磷酸化mTOR、p62蛋白表达水平增加(P<0.05);与Vec组相比,NOD2组LC3、AMPK蛋白表达水平增加(P<0.05),磷酸化mTOR、p62蛋白表达水平减少(P<0.05)。与shNC组相比,shNOD2组GFP-mRFP-LC3的点积累减少(P<0.05);与Vec组相比,GFP-mRFP-LC3的点积累增加(P<0.05)。结论 NOD2可能通过AMPK/mTOR信号促进CC增殖、迁移和侵袭,其作用机制部分涉及自噬激活。

黄芩苷调节cAMP/PKA/CREB信号通路对湿疹大鼠皮肤屏障功能的影响

目的探讨黄芩苷(BA)调节环磷酸腺苷(cAMP)/蛋白激酶A(PKA)/cAMP反应元件结合蛋白(CREB)通路对湿疹大鼠皮肤屏障功能的影响。方法将SD大鼠随机分为对照组(NC组)、Model组、低剂量BA组(BA-L组,25 mg/kg)、中剂量BA组(BA-M组,50 mg/kg)、高剂量BA组(BA-H组,100 mg/kg)、泼尼松组(PNS组,25 mg/kg)、BAH+cAMP抑制剂(SQ22536)组(100 mg/kg+2.13 mg/kg)、BA-H+PKA抑制剂(H-89)组(100 mg/kg+5 mg/kg),每组12只。除NC组外,其余组大鼠均构建湿疹大鼠模型。建模成功2 d后,分组进行给药处理。检测湿疹面积及严重度指数(EASI)评分、经皮肤水分流失量(TEWL)、角质层含水量(WCSC)变化;酶联免疫吸附试验(ELISA)检测大鼠血清中免疫球蛋白E(IgE)、干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)水平及大鼠背部受试区皮损组织中c AMP蛋白表达;HE染色检测大鼠背部受试区皮损组织病理变化;Western blot检测大鼠背部受试区皮损组织中水通道蛋白3(AQP3)、cathelicidin相关抗菌肽(CRAMP)、p-PKA、p-CREB蛋白表达。结果与NC组比较,Model组大鼠背部受试区皮损组织病理损伤严重,EASI评分、TEWL、IgE、IL-4水平升高,WCSC、IFN-γ水平、AQP3、CRAMP、cAMP、p-PKA、p-CREB蛋白水平降低(P<0.05)。与Model组比较,BA-L组、BA-M组、BA-H组、PNS组大鼠背部受试区皮损组织病理损伤减轻,EASI评分、TEWL、IgE、IL-4水平降低,WCSC、IFN-γ水平、AQP3、CRAMP、cAMP、p-PKA、p-CREB蛋白水平升高(P<0.05);且BA-L组、BA-M组、BA-H组上述指标变化呈剂量依赖性。SQ22536或H-89减弱了高剂量BA对湿疹大鼠皮肤屏障功能的改善作用。结论BA可能通过激活cAMP/PKA/CREB信号通路改善湿疹大鼠皮肤屏障功能。

川陈皮素调节AMPK/NLRP3信号通路对脂多糖诱导的肾小球系膜细胞炎性损伤的影响

目的探讨川陈皮素(Nobiletin)调节AMP激活的蛋白激酶(AMPK)/NOD样受体蛋白3(NLRP3)信号通路对脂多糖(LPS)诱导的肾小球系膜细胞HBZY-1炎性损伤的影响。方法将HBZY-1细胞分为5组:正常组、LPS组(100 ng·m L^(-1)LPS)、川陈皮素组(100 ng·m L^(-1)LPS+40μmol·L^(-1)川陈皮素)、AMPK/NLRP3信号通路抑制剂雷帕霉素组(100 ng·m L^(-1)LPS+0.5μmol·L^(-1)雷帕霉素)、川陈皮素+雷帕霉素组(100 ng·m L^(-1)LPS+40μmol·L^(-1)川陈皮素+0.5μmol·L^(-1)雷帕霉素)。MTT法检测HBZY-1细胞毒性和增殖;ELISA法检测HBZY-1细胞白细胞介素(IL)-1β、IL-6、肿瘤坏死因子α(TNF-α)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)含量;流式细胞术检测细胞凋亡;Western Blot法检测AMPK/NLRP3信号通路蛋白水平。结果与正常组比较,LPS组CAT、SOD、GSH水平、细胞OD值以及AMPK蛋白水平明显降低(P<0.05),细胞凋亡率、IL-1β、IL-6、TNF-α含量以及NLRP3蛋白水平明显升高(P<0.05)。与LPS组比较,川陈皮素组CAT、SOD、GSH水平、OD值以及AMPK蛋白水平明显升高(P<0.05),细胞凋亡率、IL-1β、IL-6、TNF-α含量以及NLRP3蛋白水平明显下降(P<0.05);而雷帕霉素组以上指标均呈现与川陈皮素组相反的趋势(P<0.05)。与川陈皮素组比较,川陈皮素+雷帕霉素组以上指标均呈现与川陈皮素组相反的趋势(P<0.05)。结论川陈皮素可能通过上调AMPK/NLRP3信号通路减轻LPS诱导的肾小球系膜细胞细胞炎性损伤。下调AMPK/NLRP3信号通路可消除川陈皮素对LPS诱导的肾小球系膜细胞细胞炎性损伤的改善作用。

基于AMPK通路探讨茶多酚改善糖尿病大鼠糖脂代谢机制

目的:探讨茶多酚从AMP活化蛋白激酶(AMPK)通路途径调控糖尿病大鼠糖脂代谢的机制。方法:经糖耐量试验筛选6周龄SD大鼠45只,按随机数字表法分为正常组10只和造模组35只,造模组糖尿病造模成功后剩余30只,根据体质量分层法和血糖水平分为模型组、二甲双胍组和茶多酚组,每组各10只。各组均于每日下午灌胃,正常组与模型组给予无菌生理盐水,二甲双胍组给予二甲双胍水溶液,茶多酚组给予茶多酚。干预120 d后,检测各组大鼠的空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C);酶联免疫吸附试验法检测肝脏乙酰辅酶A羧化酶(ACC)和激素敏感性脂肪酶(HSL);实时荧光定量法检测肝脏ACCmRNA、转录因子胆固醇调节元件结合蛋白1(SREBP-1)mRNA、3-羟基-3-甲基戊二酸单酰辅酶A还原酶(HMGCR)mRNA;免疫印迹法检测肝脏AMPKα1、磷酸化AMP活化蛋白激酶α1(P-AMPKα1)、SREBP1、HMGCR、肉毒碱棕榈酰转移酶1(CPT1)、葡萄糖转运蛋白4(GLUT4)和磷酸烯醇丙酮酸羧化激酶(PEPCK)。结果:与正常组比较,模型组大鼠的一般情况较差,FBG、TG、TC、LDL-C、ACC升高(P<0.05),SREBP1、HMGCR蛋白及mRNA表达升高(P<0.05),CPTI、PEPCK蛋白表达升高(P<0.05),HDL-C、HSL降低(P<0.05),AMPKα1、P-AMPKα1、GLUT4蛋白表达降低(P<0.05)。与模型组比较,茶多酚组大鼠的一般情况改善,TG、LDL-C、ACC降低(P<0.05),SREBP1、HMGCR蛋白及mRNA表达降低(P<0.05),PEPCK蛋白表达降低(P<0.05),HDL-C、HSL升高(P<0.05),AMPKα1、P-AMPKα1、GLUT4、CPT1蛋白表达升高(P<0.05)。与二甲双胍组比较,茶多酚组TC升高(P<0.05),FBG、TG、LDL-C、HDL-C、HSL、ACC、ACC mRNA、HMGCR mRNA、SREBP1 mRNA、AMPKα1、P-AMPKα1、SREBP1、HMGCR、CPT1、GLUT4、PEPCK相对表达量差异无统计学意义(P>0.05)。结论:茶多酚可能通过调节AMPK通路,影响HSL、HMGCR、SREBP1、CPTI、GLUT4和PEPCK,从而改善糖尿病大鼠糖脂代谢。

阿江榄仁酸由AMPK/mTOR/HO-1信号通路调控自噬对糖尿病视网膜病变影响

目的探讨阿江榄仁酸(arjunolic acid,AA)对糖尿病视网膜病变(diabetic retinopathy,DR)大鼠视网膜细胞自噬及AMPK/mTOR/HO-1信号通路的影响。方法以健康SD大鼠为研究对象,构建链脲佐菌素(STZ)诱导的糖尿病大鼠模型,随机分为对照组(Con)组、模型(STZ)组、AA低剂量(AAL,10 mg/kg)组和AA高剂量(AAH,10 mg/kg)组。连续给药10周后,HE染色检测视网膜组织病理结构;qRT-PCR检测视网膜组织白介素(IL)-1β、IL-6和线粒体丙酮酸转运载体(MPC)-1的mRNA表达;二氢乙锭(DHE)染色评估视网膜组织ROS产生;Western blot检测自噬和AMPK/mTOR/HO-1信号通路相关蛋白表达。结果与Con组比较,STZ组大鼠视网膜出现肿胀和空泡样变化等病理变化,中央视网膜ONL层厚度和细胞核计数明显降低(P<0.01);IL-1β、IL-6和MCP-1的mRNA水平显著增高(P<0.05);视网膜外核层(ONL)、内核层(INL)和神经节细胞层(GCL)中ROS产生增加(P<0.01);LC3II/I比率、HO-1和p-AMPK/AMPK蛋白表达显著降低,p62和p-mTOR/mTOR表达升高(P<0.01)。与STZ组比较,AAL和AAH组大鼠视网膜ONL厚度和细胞核计数逐渐升高,结构相对规整(P<0.05);AAH组IL-1β、IL-6和MCP-1的mRNA表达明显降低(P<0.05);视网膜ONL、INL和GCL中ROS产生逐渐降低(P<0.01);LC3II/I比率、p-AMPK/AMPK和HO-1表达逐渐升高,p62和p-mTOR/mTOR表达逐渐降低(P<0.01)。结论阿江榄仁酸可能是治疗DR的候选药物,可能机制为通过AMPK/mTOR/HO-1调节的自噬途径保护视网膜细胞免受STZ诱导的氧化应激和炎症损伤。

基于AMPK/sirt1/RANKL/OPG通路研究补阳还五汤促进骨质疏松性骨折大鼠愈合的机制

目的基于AMP活化蛋白激酶(AMPK)/沉默信息调节因子(sirt)1/核转录因子(NF)-κB受体活化蛋白配体(RANKL)/骨保护素(OPG)信号通路,探究补阳还五汤促进骨质疏松性骨折大鼠骨折愈合的机制。方法将大鼠随机分成假手术组、模型组、补阳还五汤低剂量组(6.25 g/kg)、补阳还五汤中剂量组(12.50 g/kg)和补阳还五汤高剂量组(25.00 g/kg)。除假手术组外,其余组均构建骨质疏松性骨折模型,并给予相应剂量药物干预。检测大鼠骨密度(BMD)值、骨折愈合评分及骨痂体积;自动生化分析仪测定血清碱性磷酸酶(ALP)、骨钙素、钙和磷水平;酶联免疫吸附试验(ELISA)检测股骨组织中的丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)水平;苏木素-伊红(HE)染色观察各组大鼠骨痂组织的病理形态;Western印迹检测股骨组织中AMPK/sirt1/RANKL/OPG通路蛋白表达。结果与假手术组相比,模型组骨痂骨小梁分布稀疏,成骨细胞大量减少且有纤维组织生成,骨痂体积、血清中ALP、骨钙素、钙和磷水平及股骨组织中MDA水平、RANKL蛋白水平显著升高(P<0.05),BMD值、骨折愈合评分、骨组织中SOD和GSH-Px水平和AMPK、sirt1、OPG蛋白水平显著降低(P<0.05)。与模型组相比,补阳还五汤低、中、高剂量组骨痂骨小梁分布较为密集,成骨细胞增加,骨痂体积、血清中ALP、骨钙素、钙和磷水平及股骨组织中MDA水平、RANKL蛋白水平显著降低(P<0.05),BMD值、骨折愈合评分、骨组织中SOD和GSH-Px水平和AMPK、sirt1、OPG蛋白水平显著升高(P<0.05)。结论补阳还五汤可能通过抑制氧化应激反应,调节AMPK/sirt1/RANKL/OPG通路,发挥对骨质疏松骨折大鼠的治疗作用。