Review of the pharmacological effects of astragalosideⅣand its autophagic mechanism in association with inflammation

Astragalus membranaceus Bunge,known as Huangqi,has been used to treat various diseases for a long time.AstragalosideⅣ(AS-Ⅳ)is one of the primary active ingredients of the aqueous Huangqi extract.Many experimental models have shown that AS-Ⅳexerts broad beneficial effects on cardiovascular disease,nervous system diseases,lung disease,diabetes,organ injury,kidney disease,and gynaecological diseases.This review demonstrates and summarizes the structure,solubility,pharmacokinetics,toxicity,pharmacological effects,and autophagic mechanism of AS-Ⅳ.The autophagic effects are associated with multiple signalling pathways in experimental models,including the PI3KI/Akt/m TOR,PI3KⅢ/Beclin-1/Bcl-2,PI3K/Akt,AMPK/m TOR,PI3K/Akt/m TOR,SIRT1–NF-κB,PI3K/AKT/AS160,and TGF-β/Smad signalling pathways.Based on this evidence,AS-Ⅳcould be used as a replacement therapy for treating the multiple diseases referenced above.

AstragalosideⅣameliorates insulin induced insulin resistance in HepG2 cells through reactive oxygen species mediated c-Jun N-terminal kinase pathway

OBJECTIVE:To investigate the effects and elucidate the mechanism of Astragaloside IV(AS-IV)for insulin resistance(IR)and type 2 diabet es mellitus(T2DM).METHODS:CCK8 kit was used to detect cell viability,glucose detection kit was used to detect the concentration of glucose in cell supernatant,reactive oxygen species(ROS)detection kit and Western blot were used to explore the mechanism of Astragaloside IV(AS-IV)in improving IR.A diabetic rat model was also established by feeding high sugar and fat diet and streptozotocin(STZ)injection.After treatment with AS-IV,rosiglitazone(ROZ),or normal saline,the fasting blood glucose(FBG),C peptide(C-P),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and the glucose tolerance were assessed.RESULTS:AS-IV could effectively reduce the content of ROS and increase the glucose uptake in high insulintreated IR-type HepG 2 cells.The results of molecular mechanisms indicated that AS-IV could improve insulin resistance by reducing JNK phosphorylation and regulating c-Jun N-terminal kinase(JNK)downstream protein expression.Additionally,AS-IV could significantly reduce the levels of FBG,TNF-α,IL-6 and the glucose tolerance in diabetic rats(P<0.05 or<0.01).The high and medium dose groups of AS-IV could significantly increase the C-P levels in diabetic rats(P<0.05 or<0.01).CONCLUSIONS:Our results indicated that AS-IV improve liver IR through the JNK pathway and ROS,which meant a new molecular target for the treatment of diabetes.The AS-IV also helped to prevent and improved the insulin resistance of rats.

AstragalosideⅣplays a role in reducing radiation-induced liver inflammation in mice by inhibiting thioredoxin-interacting protein/nod-like receptor protein 3 signaling pathway

OBJECTIVE:To investigate the efficacy of Astragaloside IV(AS-IV)on radiation-induced liver inflammation in mice.METHODS:The mice were divided into normal group,dimethyl sulfoxide solvent group,irradiation group(IR),irradiation+AS-IV(20 mg/kg)group(IR+AS-20)and irradiation+AS-IV(40 mg/kg)group(IR+AS-40).One month after intraperitoneal injection of AS-IV,the mice were irradiated with 8Gry Co60γ,the blood was collected for biochemical analysis,and the liver was collected for hematoxylin-eosin staining,immunofluorescence and electron microscopic observation,oxidative stress,and Western blot analysis.RESULTS:The AS-IV treatment significantly ameliorated the pathological morphology of liver and reduced the alanine aminotransferase and aspertate aminotransferase levels in serum induced by radiation;AS-IV treatment also significantly reduced the expression of inflammatory factors tumor necrosis factor alpha and interleukin 6 and antagonized malonaldehyde content and superoxide dismutase activity in liver caused by radiation;in addition,AS-IV treatment can significantly inhibited the positive expression of thioredoxin-interacting protein(TXNIP)and nod-like receptor protein 3(NLRP3)inflammasome in liver tissue after radiation;The expression of TXNIP,NLRP3 inflammasome,apoptosisassociated speck-like protein containing a CARD,cysteinyl aspartate-specific proteinase 1 and interleukin 1beta in the AS-IV prevention group decreased significantly compared to the radiation group.CONCLUSIONS:These findings suggested that Co60γradiation can cause structural and functional damage to the liver,which may be related to the NLRP3 mediated inflammatory pathway;AS-IV may play a protective role by inhibiting the TXNIP/NLRP3 inflammasome signaling pathway in the radiation-induced liver injury model.

Effect of astragaloside Ⅳ on lipid and glucose metabolism in acute myocardial infarction through PPARγ pathway

OBJECTIVE To investigate the effects of astragaloside IV(which can be extracted from the traditional Chinese medicine Astragalus membranaceus)on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS Model of heart failure(HF)after AMI was established with ligation of left anterior descending artery on Sprague-Dawley(SD)rats.The rats were divided into three groups:sham,model and astragaloside IV treatment group.Twenty-eight days after treatment(astragaloside IV,20 mg·kg-1 daily),hematoxylin-eosin(HE)staining was applied to visualize cardiomyocyte morphological changes.High performance liquid chromatography(HPLC)was performed to assess the contents of adenosine phosphates in heart.Positron emission tomography and computed tomography(PET-CT)was conducted to evaluate the cardiac glucose metabolism.Expressions of key molecules such as peroxisome proliferatoractivated receptor γ(PPARγ),sterol carrier protein 2(SCP2)and long chain acyl CoA dehydrogenase(ACADL)were measured by Western blotting and immunohistochemistry.Oxygen-glucose deprivation-reperfusion(OGD/R)-induced H9C2 injury cardiomyocyte model was adopted for potential mechanism research in vitro.RESULTS Treatment with astragaloside Ⅳ rescued hearts from structural and functional damages as well as inflammatory infiltration.Levels of adenosine triphosphate(ATP)and energy charge(EC)in astragaloside IV group were also up-regulated compared to model group.Further results demonstrated that critical enzymes both in lipid metabolism and glucose metabolism compro mised in model group compared to sham group.Intriguingly,astragalosideⅣcould up-regulate critical enzymes including ACADL and SCP2 in lipid metabolism accompanying with promoting effect on molecules in glycolysis simultaneously.Results on upstreaming signaling pathway demonstrated that astragaloside Ⅳ could dramatically increase the expres sions of PPARγ.In vitro study suggested the efficacy of astragalosideⅣcould be blocked by T0070907,a selective PPARγ inhibitor.CONCLUSION Astragaloside IV has cardioprotective effect in improving cardiac function and energy metabolism through regulating lipid and glucose metabolism.The effects may be mediated by PPARγ pathway.

CroweⅢ-Ⅳ型DDH患者全髋关节置换术后不满意及相关因素分析

目的:探讨全髋关节置换术的CroweⅢ-Ⅳ型发育性髋关节发育不良(developmental dysplasia of the hip,DDH)患者的满意度及造成不满意的相关因素。方法:回顾性分析2013年3月至2018年3月行全髋关节置换术的169例CroweⅢ-Ⅳ型DDH患者,通过微信进行调查问卷,调查患者对手术总体满意度、10项日常功能满意度和患者认为对自己日常生活影响比较大的前5个问题。手术前后采用髋关节Harris评分进行功能评价。结果:收到完整调查问卷145份,所有患者获随访,时间1~5(3.23±1.22)年。145例患者分成两组,其中对手术疗效满意的118例,不满意的27例,手术总体满意率81.38%(118/145)。患者认为对生活影响比较大的前5个问题分别是术后髋部疼痛,肢体明显不等长、行走、上下楼梯、蹲起。两组术前Harris评分比较,差异无统计学意义(P>0.05),不满意组术后Harris评分较低。术后髋关节疼痛、肢体不等长是影响手术不满意的直接因素。结论:采用全髋关节置换术治疗CroweⅢ-Ⅳ型DDH患者手术难度大;术后髋关节疼痛(轻度以上),肢体不等长(>2 cm)是术后不满意的独立危险因素。

辽宁第Ⅳ金刚石成矿带东部潘家沟辉绿岩中铬铁矿的矿物化学特征及其意义

辽宁省永宁地区因发现原生金刚石而被划分为辽宁第Ⅳ金刚石成矿带,但尚未厘定出金刚石的来源,有必要加强对与金刚石伴生的指示矿物的研究。对该成矿带东部潘家沟地区辉绿岩中选获的铬铁矿开展电子探针成分分析,并与辽宁典型金伯利岩管中的铬铁矿成分进行对比,以探讨该地区铬铁矿的成因及其与金刚石的关系。根据铬铁矿样品电子探针背散射图像显示的粒径、形态及熔蚀特征,以及铬铁矿电子探针成分测试显示的高Cr、富Mg、低Al及贫Ti的特征,推测该地区的铬铁矿来自地幔捕掳晶,属于镁铬铁矿亚类,主要为镁铁-铬铝铁亚种和镁铁-铬铝亚种。计算得到铬铁矿的形成温度为1 252~1 307℃,与前人报道的瓦房店典型金伯利岩中铬铁矿的形成温度基本一致,也接近金刚石的形成温度,表明潘家沟地区辉绿岩中铬铁矿的成因与金刚石关系密切,该地区具有良好的金刚石成矿潜力和找矿前景。研究成果对潘家沟地区金刚石原生矿的勘查及探明该地区金刚石的来源具有指导意义。

二肽基肽酶-Ⅳ有机小分子荧光探针的研究进展

二肽基肽酶-IV(DPP-IV)是一种重要的跨膜糖蛋白水解酶,与各种生理过程和疾病密切相关,检测DPP-IV的有机小分子荧光探针被相继报道,是当前研究生物酶检测的热点。首次综述了用于DPP-IV体外和体内检测及成像的3类有机小分子荧光探针,分别是非近红外荧光探针(λ_(em)<650nm)、近红外荧光探针(λ_(em)>650nm)和双光子荧光探针,对比并总结了三种探针的设计原理、结构特点、生物应用情况及其在DPP-IV相关疾病诊断中的应用,并探讨了DPP-IV活性检测在未来发展方向上所面临的挑战。

经食管超声心动图在肾切除术联合MayoⅢ~Ⅳ级静脉瘤栓取栓术不同手术方式中的临床作用

目的:比较经食管超声心动图(transesophageal echocardiography,TEE)在肾切除术联合下腔静脉MayoⅢ~Ⅳ级瘤栓取栓术不同手术方式中的临床作用。方法:纳入2022年1月至2024年2月在北京大学第三医院行根治性肾切除联合MayoⅢ~Ⅳ级瘤栓取栓手术的患者28例,其中,机器人手术16例,腹腔镜手术2例,开腹手术10例,收集患者的各项临床资料进行分析比较。结果:机器人手术的患者中有9例采用TEE,其中7例术中TEE影像结果较术前发生变化,包括2例术中TEE提示瘤栓进入右心房,2例显示下腔静脉瘤栓由MayoⅢ级升至Ⅳ级,3例提示瘤栓与下腔静脉粘连,及时调整了手术方案;开腹手术的患者中有6例采用TEE,其中4例术中TEE提示Mayo分级较术前发生变化,包括3例提示瘤栓与下腔静脉粘连,1例提示瘤栓伴血栓形成,调整了手术方案,旷置或节段性切除瘤栓;腹腔镜手术的2例患者未采用术中TEE。术中采用TEE的作用包括开腹手术术中探查结合TEE监测瘤栓切除过程,机器人手术完全通过TEE监测瘤栓脱出,术中TEE还实时监测患者循环状态和心脏功能变化。结论:肾切除术联合MayoⅢ~Ⅳ级瘤栓取栓术的不同术式中,术中TEE均可再次确定瘤栓分级、粘连程度,并实时动态跟踪取栓过程,监测患者循环状态和心脏功能变化,具有重要的辅助作用,但其临床应用仍不足,建议这类手术均采用术中TEE。

热淋清颗粒治疗尿路感染的多中心、开放性、Ⅳ期临床研究

目的评价热淋清颗粒在临床使用中的安全性与有效性,以指导优化临床给药方案和提高合理用药水平。方法在51家医院进行开放性、Ⅳ期临床试验,受试者为下焦湿热型单纯性或复杂性尿路感染,单纯性尿路感染患者给予热淋清颗粒每次8 g、每天3次,疗程5 d。复杂性尿路感染患者给予热淋清颗粒每次8 g、每天3次,同时联合喹诺酮类抗生素,疗程7~14 d。结局指标为临床疗效、中医证候疗效、细菌清除率以及安全性。结果共纳入2009例受试者,其中11患者失访脱落。全分析集纳入1998例,其中单纯性尿路感染患者1532例,复杂性尿路感染患者466例。临床治愈率为68.57%,单纯性和复杂性尿路感染患者分别为74.41%和49.36%。中医证候痊显率为72.22%,单纯性和复杂性尿路感染患者分别为75.13%和62.66%。单纯性尿路感染中细菌培养阳性者的细菌转阴率为57.75%,细菌清除率为58.02%;复杂性尿路感染中细菌培养阳性者的细菌转阴率为45.59%,细菌清除率为43.92%。药物相关的不良反应发生24例次,其中单纯性尿路感染17例次,复杂性尿路感染7例次。结论热淋清颗粒治疗单纯性尿路感染的有效性和安全性较好,也可改善下焦湿热证中医证候。

纳武利尤单抗联合安罗替尼对Ⅲb~Ⅳ期NSCLC的疗效观察及对miR-1269、miR-204-5p表达的影响

目的探究纳武利尤单抗联合安罗替尼治疗Ⅲb~Ⅳ期非小细胞肺癌(NSCLC)患者的效果及对微小RNA-1269(miR-1269)、miR-204-5p表达的影响。方法选取Ⅲb~Ⅳ期NSCLC患者82例,患者分配为对照组、观察组,各41例,使用随机数字表法,对照组采用安罗替尼治疗,观察组在对照组的基础上采用纳武利尤单抗治疗;比较两组患者的疗效、治疗前后肿瘤标志物癌胚抗原(CEA)、细胞角蛋白19片段抗原21-1(CYFRA21-1)、miR-1269、miR-204-5p表达水平和不良反应的发生率。结果观察组患者治疗后疾病控制率(87.80%,36/41)显著高于对照组(68.29%,28/41)(χ^(2)=4.556,P=0.033);与治疗前相比,治疗后观察组和对照组的CEA、CYFRA21-1、miR-1269水平显著降低,miR-204-5p水平显著升高(P<0.05);治疗后与对照组相比,观察组的CEA、CYFRA21-1、miR-1269水平显著降低,miR-204-5p水平显著升高(P<0.05);不良反应两组间比较,差异无统计学意义(P>0.05)。结论纳武利尤单抗联合安罗替尼治疗Ⅲb~Ⅳ期NSCLC患者可降低患者肿瘤标志物的水平,调节miR-1269、miR-204-5p的表达,效果更好。

1例糖原累积病Ⅳ型合并急性肝衰竭患儿急性期的护理

总结2022年7月我科收治的1例糖原累积病Ⅳ型(glycogen storage disease typeⅣ,GSDⅣ)合并急性肝衰竭患儿急性期的护理经验。护理要点:监测血流动力学,积极抗休克;监测消化道出血量,实施止血治疗;开展人工肝治疗及预防相关并发症;连续监测血糖,根据病情与血糖动态调整营养治疗方案;开展远程探视和音乐治疗。经过6 d的救治和护理,患儿病情好转,顺利进行肝移植。术后18 d好转出院;随访1年,恢复良好。

老年Ⅳ~Ⅴ级颅内动脉瘤介入栓塞术中血压管理策略对预后的影响

目的:探究介入栓塞术中不同血压管理策略对老年Ⅳ~Ⅴ级颅内动脉瘤患者的预后影响。方法:回顾性选取我院收治的老年Ⅳ~Ⅴ级颅内动脉瘤患者110例,并纳入训练集。使用随机数字表法将患者分为观察组(55例)和对照组(55例),比较训练集两组患者的临床资料;使用Kaplan-Meier法进行生存曲线的绘制,比较不同血压管理策略患者的2年预后不良发生率;Cox单因素和多因素回归分析患者术后预后不良的影响因素;构建预测患者术后预后不良的列线图模型;通过验证集患者以受试者工作特征曲线(ROC)和校准曲线对模型效能进行评价。依据模型预测个体风险评分,构建危险分层系统。结果:观察组患者的2年预后不良发生率明显低于对照组(P<0.05);高血压、手术时机为中期和晚期、平均动脉压≥65 mmHg、血压波动幅度≥16 mmHg、瘤体长径与瘤颈宽度的比值(AR)>2.0是老年Ⅳ~Ⅴ级颅内动脉瘤患者介入栓塞术预后不良的独立危险因素(P<0.05),术中血压管理策略为控制性降压是老年Ⅳ~Ⅴ级颅内动脉瘤患者介入栓塞术预后不良的保护因素(P<0.05);列线图预测模型有较好的区分度及准确度。危险分层系统将所有患者分为4个危险分组:极低风险组(总分<30分)、低风险组(30分≤总分<78分)、中风险组(78分≤总分<106分)和高风险组(总分≥106分)。该危险分层系统能区分不同术中血压管理策略患者的预后不良发生情况(P<0.05)。结论:在手术过程中应实施瑞芬太尼联合尼莫地平控制性降压的血压管理策略,可以提高患者的预后水平。

心脏瓣膜置换术同期行Cox-MazeⅣ射频消融治疗心脏瓣膜病的临床观察

目的:观察心脏瓣膜置换术同期行Cox-MazeⅣ射频消融治疗对心脏瓣膜病患者临床指标的影响。方法:采用分类随机抽样法抽取郑州市第七人民医院2022年1月至2024年1月期间收治的78例心脏瓣膜病患者纳入研究,将其中采用单纯心脏瓣膜置换术治疗的39例患者纳入单纯组,将其中采用心脏瓣膜置换术同期行Cox-MazeⅣ射频消融治疗的39例患者纳入同期组。结果:同期组患者主动脉阻断时间、体外循环时间、住院时间均长于单纯组,差异具有统计学意义(P<0.05)。术后24 h,同期组患者肌酸激酶(CK)、心肌肌钙蛋白I(cTnI)水平均高于单纯组,差异具有统计学意义(P<0.05)。术后第1天、出院时、术后1个月,同期组患者窦性心率复转率均高于单纯组,差异具有统计学意义(P<0.05)。术后1个月,同期组患者左心室射血分数(LVEF)、每博输出量(SV)、心脏指数(CI)均高于单纯组,差异具有统计学意义(P<0.05)。两组患者术后并发症发生率比较,差异无统计学意义(P>0.05)。结论:心脏瓣膜置换术同期行Cox-MazeⅣ射频消融治疗可更好的改善患者术后心功能,提高术后窦性心率复转率,且治疗方案安全可行。

Ⅳ型LPG气瓶冲击试验的国内外标准探讨

T/CATSI 02005—2019《液化石油气高密度聚乙烯内胆玻璃纤维全缠绕气瓶》的编制是在理论分析和研究的基础上,修改采用了EN14427:2014《液化石油气设备及配件用于液化石油气的可运输的可充填全封闭复合气瓶设计和施工》有关热塑性非金属内胆全缠绕气瓶部分制定的。通过对冲击试验结果进行分析来探讨T/CATSI 02005—2019和EN14427:2014两个标准的差异性。建议在不影响试验结果的前提下优化试验方法,验证气瓶受外来物体冲击后的抗冲击性能,同时保障试验过程中的生命、财产安全。

Astragaloside Ⅳ inhibits pathological functions of gastric cancer-associated fibroblasts

AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts,and to explore the underlying mechanism.METHODS Paired gastric normal fibroblast(GNF) and gastric cancer-associated fibroblast(GCAF) cultures were established from resected tissues. GCAFs were treated with vehicle control or different concentrations of astragaloside Ⅳ. Conditioned media were prepared from GNFs,GCAFs,control-treated GCAFs,and astragaloside Ⅳ-treated GCAFs,and used to culture BGC-823 human gastric cancer cells. Proliferation,migration and invasion capacities of BGC-823 cells were determined by MTT,wound healing,and Transwell invasion assays,respectively. The action mechanism of astragaloside Ⅳ was investigated by detecting the expression of micro RNAs and the expression and secretion of the oncogenic factor,macrophage colonystimulating factor(M-CSF),and the tumor suppressive factor,tissue inhibitor of metalloproteinase 2(TIMP2),in different groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and NANOG in BGC-823 cells cultured with different conditioned media was also examined.RESULTS GCAFs displayed higher capacities to induce BGC-823 cell proliferation,migration,and invasion than GNFs(P < 0.01). Astragaloside Ⅳ treatment strongly inhibited the proliferation-,migration-and invasion-promoting capacities of GCAFs(P < 0.05 for 10 μmol/L,P < 0.01 for 20 μmol/L and 40 μmol/L). Compared with GNFs,GCAFs expressed a lower level of micro RNA-214(P < 0.01) and a higher level of micro RNA-301 a(P < 0.01). Astragaloside Ⅳ treatment significantly upregulated micro RNA-214 expression(P < 0.01) and down-regulated micro RNA-301 a expression(P < 0.01) in GCAFs. Reestablishing the micro RNA expression balance subsequently suppressed M-CSF production(P < 0.01) and secretion(P < 0.05),and elevated TIMP2 production(P < 0.01) and secretion(P < 0.05). Consequently,the ability of GCAFs to increase SOX2 and NANOG expression in BGC-823 cells was abolished by astragaloside Ⅳ.CONCLUSION Astragaloside Ⅳ can inhibit the pathological functions of GCAFs by correcting their dysregulation of micro RNA expression,and it is promisingly a potent therapeutic agent regulating tumor microenvironment.

入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平与CHB肝纤维化严重程度的相关性及对疾病预后的预测价值

目的探讨入院时血清转化生长因子-β1(TGF-β1)、Smad同源蛋白2(Smad2)、Smad同源蛋白3(Smad3)及透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层黏连蛋白(LN)、Ⅳ型胶原(CⅣ)水平与慢性乙型肝炎(CHB)肝纤维化严重程度的相关性及联合检测对疾病预后的预测价值。方法选取河南省中医院2021年3月至2022年3月收治的78例CHB肝纤维化患者作为研究组,选择同期78名健康体检者作为对照组。比较研究组和对照组及不同肝纤维化分期、不同炎症活动分级CHB肝纤维化患者入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平;分析入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平与肝纤维化分期、炎症活动分级的相关性。CHB肝纤维化患者治疗3个月后,根据患者预后分为预后良好和预后不良亚组,比较预后良好和预后不良患者入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平;分析入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平联合检测对CHB肝纤维化患者预后不良的预测价值。结果研究组入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ高于对照组(P<0.05);不同肝纤维化分期、炎症活动分级CHB肝纤维化患者入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ比较:S1<S2<S3<S4、G1<G2<G3<G4,差异有统计学意义(P<0.05);入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平与肝纤维化分期、炎症活动分级均呈正相关(P<0.05)。预后良好患者入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平均低于预后不良患者(P<0.05);入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平联合预测肝纤维化患者预后不良的曲线下面积(AUC)优于各指标单一检测(P<0.05)。结论CHB肝纤维化患者入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平均呈现高表达,且与肝纤维化分期、炎症活动分级密切相关,其联合检测对CHB肝纤维化患者预后有较高的预测价值,可用于评估CHB肝纤维化患者病情严重程度和预后,为制定针对性治疗措施提供参考。

黄芪甲苷Ⅳ通过抑制TIM-1信号通路增加Th1/Th2细胞比率减轻IgA肾病小鼠肾损伤

目的探讨黄芪甲苷Ⅳ(AS-Ⅳ)对IgA肾病(IgAN)小鼠1型辅助T(Th1)细胞/Th2细胞平衡的影响及其可能作用机制。方法建立BALB/c小鼠IgAN模型,造模成功小鼠随机分为模型组、AS-Ⅳ低、中和高剂量组各10只,另设对照组10只。AS-Ⅳ低、中和高剂量组小鼠灌胃(12.5、25、50)mg/kg AS-Ⅳ混悬液(生理盐水配制),对照组及模型组给予等量生理盐水。测定各组小鼠24 h尿蛋白(24 hUPr)含量和尿红细胞计数;测定小鼠血尿素氮(BUN)、血清肌酐(Scr)和白蛋白(ALB)水平;ELISA检测各组小鼠血清γ干扰素(IFN-γ)、白细胞介素4(IL-4)和IL-10水平;流式细胞术检测小鼠外周血Th1/Th2细胞比率;HE染色观察小鼠肾组织病理学变化;反转录PCR和Western blot法分别检测小鼠肾组织中T细胞免疫球蛋白和黏蛋白结构域1(TIM-1)、Toll样受体4(TLR4)的mRNA和蛋白表达。结果与模型组比较,AS-Ⅳ低、中和高剂量组小鼠第12周和第15周尿红细胞计数、24 h UPr、BUN、Scr、IL-4、IL-10水平、Th2细胞比例、TIM-1与TLR4 mRNA和蛋白表达水平均明显降低,ALB、IFN-γ水平、Th1细胞比例和Th1/Th2细胞比率升高,且以AS-Ⅳ高剂量组效果最佳。结论AS-Ⅳ通过抑制TIM-1信号通路,增加Th1/Th2细胞比率,抑制炎症反应,减轻IgAN小鼠肾损伤。

The mechanism of astragaloside Ⅳ promoting sciatic nerve regeneration

3-O-beta-D-xylopyranosyl-6-O-beta-D-glucopyranosyl-cycloastragenol （astragaloside IV）, the main active component of the traditional Chinese medicine astragalus membranaceus, has been shown to be neuroprotective. This study investigated whether astragaloside IV could promote the repair of injured sciatic nerve. Denervated sciatic nerve of mice was subjected to anastomosis. The mice were intraperitoneally injected with 10, 5, 2.5 mg/kg astragaloside IV per day for 8 consecutive days Western blot assay and real-time PCR results demonstrated that growth-associated protein-43 ex- pression was upregulated in mouse spinal cord segments L4-6 after intervention with 10, 5, 2.5 mg/kg astragaloside IV per day in a dose-dependent manner. Luxol fast blue staining and elec- trophysiological detection suggested that astragaloside IV elevated the number and diameter of myelinated nerve fibers, and simultaneously increased motor nerve conduction velocity and action potential amplitude in the sciatic nerve of mice. These results indicated that astragaloside IV con- tributed to sciatic nerve regeneration and functional recovery in mice. The mechanism underlying this effect may be associated with the upregulation of growth-associated protein-43 expression.

Content Determination of Astragaloside Ⅳ in Astragalus from Three Different Regions by HPLC

[Objectives] The content of astragaloside in Astragalus membranaceus(Fisch.) Bge.var.mongholicus(Bge.) Hisao from three different regions was determined.[Methods] Referring to the method recorded in the Chinese Pharmacopoeia(2015 edition),the content of astragaloside IV in A.membranaceus was determined by HPLC.[Results] There were great differences in the astragaloside IV content of A.membranaceus among different regions.The content of astragaloside IV in A.membranaceus cultivated in Inner Mongolia was highest(0.155%),followed by that(0.143%) in A.membranaceus cultivated in Gansu,and the content of astragaloside IV in A.membranaceus cultivated in Shanxi was lowest(0.080%).The contents of astragaloside IV in A.membranaceus from different regions were all in line with the standard(not less than 0.040%) of Chinese Pharmacopoeia(2015 edition).[Conclusions]The content of astragaloside IV in A.membranaceus cultivated in three different regions met the medicinal standards.

Astragaloside IV Ameliorates Inflammatory Damage in Mice with Acute Liver Failure

Acute liver failure is a life-threatening clinical syndrome with a high mortality rate. Currently, the research on Astragaloside IV in liver diseases primarily focuses on liver cancer, and there is limited understanding of its mechanism in acute liver failure’s innate immunity. Therefore, this study aims to investigate the potential protective effect of Astragaloside IV on acute liver failure and its impact on innate immune cells. The study employed D-GalN/LPS-induced acute liver failure mouse models and employed various techniques such as a range of molecular and analytical techniques. The experimental results demonstrated that treatment with Astragaloside IV significantly reduced the inflammatory response, alleviated liver injury, and improved the survival rate of mice with acute liver failure induced by D-GalN/LPS. Further investigations revealed that AS-IV played a beneficial role by regulating the proportion of CD11b+Ly6Chi monocytes and the secretion of inflammatory cytokines and anti-inflammatory metabolites. These findings suggest that the pharmacological mechanism of AS-IV may involve targeted regulation of CD11b+Ly6Chi monocytes in both peripheral blood and liver. The implications of this study’s results are twofold. Firstly, they provide a basis for the clinical application of AS-IV in treating liver failure, offering potential therapeutic benefits. Secondly, they serve as a reference for further development of safer and more effective modified compounds.