单不饱和脂肪酸作用机制及在糖尿病肾脏疾病中的研究进展

糖尿病肾脏疾病(diabetes kidney disease,DKD)是一种由糖尿病引起的慢性肾脏病,也是引起终末期肾病的主要原因,因此,加强DKD的防治具有重要的意义。研究表明血管紧张素转化酶抑制剂(angiotensin-converting enzyme inhibitors,ACEI)和血管紧张素受体阻滞剂(angiotensin receptor blockers,ARB)可以减弱甚至逆转蛋白尿的进展,减缓糖尿病患者肾功能的下降^([1]),但是,ACEI及ARB类药物并不能完全预防DKD。

Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system

The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

Evaluation of angiotensin converting enzyme insertion/deletion, alpha adducin (ADD1) G460W, and IL-10 gene polymorphisms, and determination of prognostic effects in idiopathic sudden sensorineural hearing loss

Objective:The aim of this study was to examine angiotensin converting enzyme(ACE)insertion/deletion,alpha adducin,and interleukin-10(IL-10)gene polymorphisms(GPs)in terms of both idiopathic sudden sensorineural hearing loss(ISSNHL)risk and their potential prognostic effects.Methods:The study group consisted of 70 patients and the control group consisted of 50 patients.Venous blood samples were analyzed for relevant GPs via kompetitive allele-specific polymerase chain reaction.Age,sex,affected side,tinnitus,and vertiginous symptom status,number of days between symptom onset and hospital admission,pure tone audiometry results at admission and after treatment were included in the study.Data were compared statistically.Results:The D allele of ACE insertion/deletion GP was significantly more frequent in patients with ISSNHL than in the control group(p=0.032).II genotype was associated with a reduced risk of ISSNHL(p=0.036).The amount of hearing loss was significantly higher in patients with the TT genotype(p=0.027)and T allele of the IL-10 GP(p=0.035)than in the patients without this allele.Severe hearing loss was a poor prognostic factor(p=0.008).Conclusions:The D allele of ACE insertion/deletion GP may be involved in the ISSNHL etiology.Due to the association of this allele with occlusive vascular pathologies,ischemia is believed to be a common pathway in the etiopathogenesis of ISSNHL.

Impacts of angiotensin II on retinal artery changes in apolipoprotein E deficient mice

AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(Ang II group)or saline(control group)for 28d.They were underwent ophthalmic fundus examination on day 0,14,and 28 of infusion.Histopathologic examination,ribonucleic acid(RNA)sequencing and local Ang II measurement of retinas were conducted.RESULTS:Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28.Optical coherence tomography revealed the ganglion cell and inner plexiform layer(GCIPL)thickness in the control group was significantly thinner than that in Ang II group(P<0.001).Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group.Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions,including increased swelling,roughness,disorganization of the retinal vasculature,and vacuoles formation.RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II.The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group(P=0.086).CONCLUSION:Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE^(-/-)mice,causing aggravation of atherosclerotic lesions,more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.

Extracellular vesicles and angiotensin-converting enzyme 2 in COVID-19 disease

Extracellular vesicles(EVs)are membranous vesicular structures released from almost all eukaryotic cell types under different physiological or pathological conditions.Growing evidence demonstrates that EVs can serve as mediators of intercellular communication between donor and recipient cells or microorganism-infected and noninfected cells.Coronavirus disease 2019(COVID-19)disease is caused by infection of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)of host cells in the respiratory system and various extra-pulmonary tissue/organs,resulting in complications of multiple organ systems.As the cell surface receptor,angiotensin-converting enzyme 2(ACE2)mediates cellular entry of SARS-CoV-2 into the host cells in patients with COVID-19.Recent studies have found that ACE2 can be released with EVs,which have been shown to interfere with the entry of the virus into host cells and thus may be involved in COVID-19 pathophysiology.In addition,ACE2,neprilysin(NEP),and thimet oligopeptidase(TOP)are the key enzymes that regulate angiotensin metabolism by converting angiotensin II or angiotensin I to angiotensin 1-7,the latter of which has protective effects in counterbalancing the harmful effects of angiotensin II in COVID-19 disease.This review summarizes the recent research progress regarding EV-associated ACE2,NEP,and TOP and the perspectives of their potential involvement in the pathophysiology of COVID-19 disease.

Biological function of miRNA-145-5p in angiotensin II induced renal inflammation

Objective:Chronic kidney disease(CKD)is a progressive disorder characterized by intricate structural and functional alterations in the kidneys,attributable to diverse causative factors.Notably,the therapeutic promise of miR-145-5p in addressing renal pathologies has been discerned.This investigation seeks to elucidate the functional role of miR-145-5p in injured kidneys by subjecting human glomerular mesangial cells(HGMCs)to stimulation with Angiotensin II(AngII).Materials and Methods:Cellular viability and the levels of inflammatory mediators were evaluated utilizing Cell Counting Kit-8(CCK-8),quantitative real-time polymerase chain reaction(qRT-PCR),and western blot methodologies,both in the presence of AngII incubation and in scenarios of miR-145p overexpression and downregulation.Furthermore,the cell cycle dynamics were elucidated through Fluorescence-activated Cell Sorting(FACS)analysis.Results:AngII incubation induced an upregulation of miR-145-5p and inflammatory factors including Intercellular Adhesion Molecule 1(ICAM-1),Interleukin 6(IL-6),Interleukin 8(IL-8),and Interleukin 1β(IL-1β).Additionally,it elevated the expression of Cyclin A2,Cyclin D1,and the G2/M cell cycle ratio.Conversely,inhibition of miR-145-5p heightened the levels of inflammatory factors and cell cycle regulators induced by AngII incubation.Reduced expression of miR-145-5p correlated with a downregulation of Interleukin 10(IL-10)expression,concurrently promoting HGMC proliferation under AngII stimulation.Moreover,ectopic miR-145-5p expression demonstrated a reduction in inflammatory factors,cell cyclin regulators,G2/M cell cycle ratio,and overall proliferation.Conclusion:MiR-145-5p exhibited inhibitory effects on the inflammatory response and proliferation induced by Angiotensin II in HGMCs,showcasing its potential as a therapeutic avenue for the treatment of kidney injury.

AGTR1 A1166C gene polymorphism is associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension:A retrospective analysis

Objective:To investigate whether angiotensinⅡtype 1 receptor(AGTR1 A1166C)gene polymorphism was associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension.Methods:This retrospective analysis included 198 patients(≥18 years of age)who received valsartan monotherapy(80 mg/day)for newly developed essential hypertension at the authors’center between January 1,2020 and December 31,2023.Genotyping for AGTR1 A1166C gene polymorphism was done by polymerase chain reaction(PCR)-melting curve analysis of genomic DNA from peripheral blood samples.A dominant genetic model for AGTR1 A1166C(AA genotype versus AC+CC genotype)was used.Multivariate regression analysis of baseline variables and AGTR1 polymorphism was conducted to identify predictors of target blood pressure attainment(<140/90 mmHg)at the 4-week follow-up.Results:The median age of the 198 patients was(53.7±13.5)years,and 58%were men.Genotyping assays showed that 164 patients had the AA genotype,and 34 patients were of the AC/CC genotype,including 30 with the AC genotype and 4 with the CC genotype.Allele distribution was consistent with Hardy Weinberg equilibrium.109 Patients(55.1%)attained the blood pressure target.Multivariate analysis showed that smoking(versus no smoking,HR 0.314,95%CI 0.159-0.619,P=0.001)and AGTR1 A1166C AA genotype(versus AC/CC,HR 2.927,95%CI 1.296-6.611,P=0.023)were significant and independent predictors of target attainment.25 Patients(73.5%)with AGTR1 A1166C AC/CC genotype attained the target versus 51.2%(51/164)of patients with AGTR1 A1166C AA genotype(P=0.017).Patients with AGTR1 A1166C AC/CC genotype had a significantly greater reduction in systolic blood pressure[(33.1±10.8)mmHg versus(29.2±11.7)mmHg in AA carriers;(P=0.029)].Conclusions:Hypertensive patients carrying one or two C alleles of the AGTR1 A1166C gene were more responsive to valsartan treatment.

Immunoglobulin A glomerulonephropathy:A review

In this editorial,we comment on the article by Meng et al published in the World Journal of Clinical Cases.We comprehensively review immunoglobulin A nephro-pathy(IgAN),including epidemiology,clinical presentation,diagnosis,and management.IgAN,also known as Berger's disease,is the most frequent type of primary glomerulonephritis(GN)globally.It is mostly found among the Asian population.The presentation can be variable,from microscopic hematuria to a rapidly progressive GN.Around 50%of patients present with single or recurring episodes of gross hematuria.An upper respiratory infection and tonsillitis often precede these episodes.Around 30%of patients present microscopic hematuria with or without proteinuria,usually detected on routine examination.The diagnosis relies on having a renal biopsy for pathology and immunofluorescence microscopy.We focus on risk stratification and management of IgAN.We provide a review of all the landmark studies to date.According to the 2021 KDIGO(kidney disease:Improving Global Outcomes)guidelines,patients with non-variant form IgAN are first treated conservatively for three to six months.This approach consists of adequate blood pressure control,reduction of proteinuria with renin-angiotensin system blockade,treatment of dyslipidemia,and lifestyle modifications(weight loss,exercise,smoking cessation,and dietary sodium restrictions).Following three to six months of conservative therapy,patients are further classified as high or low risk for disease progression.High-risk patients have proteinuria≥1 g/d or<1 g/d with significant microscopic hematuria and active inflammation on kidney biopsy.Some experts consider proteinuria≥2 g/d to be very high risk.Patients with high and very high-risk profiles are treated with immunosuppressive therapy.A proteinuria level of<1 g/d and stable/im-proved renal function indicates a good treatment response for patients on immu-nosuppressive therapy.

Role of angiotensin receptor-neprilysin inhibitor in diabetic complications

Diabetes mellitus is a prevalent disorder with multi-system manifestations,causing a significant burden in terms of disability and deaths globally.Angio-tensin receptor-neprilysin inhibitor(ARNI)belongs to a class of medications for treating heart failure,with the benefits of reducing hospitalization rates and mortality.This review mainly focuses on the clinical and basic investigations related to ARNI and diabetic complications,discussing possible physiological and molecular mechanisms,with insights for future applications.

Angiotensin II administration in severe thrombocytopenia and chronic venous thrombosis:A case report

BACKGROUND The initial trials on angiotensin II(AT II)administration indicated a high incidence of thrombocytopenia and thrombosis,as well as a positive correlation between hyperreninemia and response to the medication.CASE SUMMARY We describe a case of a patient presenting with catecholamine resistant septic shock,thrombocytopenia,deep vein thrombosis,and normal renin concentration who responded immediately to AT II treatment.We observed no worsening of thrombocytopenia and no progression of thrombosis or additional thromboses during treatment.CONCLUSION Our case underscores the need for individualized assessment of patients for potential therapy with AT II.

Influence of Angiotensin II on α1-Adrenergic Receptors Function in Rat Aorta and Expression in Vascular Smooth Muscle Cells

Angiotensin II (Ang II) is the main mediator of the Renin-Angiotensin-System acting on AT1 and other AT receptors. It is regarded as a pleiotropic agent that induces many actions, including functioning as a growth factor, and as a contractile hormone, among others. The aim of this work was to examine the impact of Ang II on the expression and function of α1-adrenergic receptors (α1-ARs) in cultured rat aorta, and aorta-derived smooth muscle cells. Isolated Wistar rat aorta was incubated for 24 h in DMEM at 37˚C, then subjected to isometric tension and to the action of added norepinephrine, in concentration-response curves. Ang II was added (1 × 10−5 M), and in some experiments, 5-Methylurapidil (α1A-AR antagonist), AH11110A (α1B-AR antagonist), or BMY-7378 (α1D-AR antagonist), were used to identify the α1-AR involved in the response. Desensitization of the contractile response to norepinephrine was observed due to incubation time, and by the Ang II action. α1D-AR was protected from desensitization by BMY-7378;while RS-100329 and prazosin partially mitigated desensitization. In another set of experiments, isolated aorta-derived smooth muscle cells were exposed to Ang II and α1-ARs proteins were evaluated. α1D-AR increased at 30 and 60 min post Ang II exposure, the α1A-AR diminished from 1 to 4 h, while α1B-AR remained unchanged over 24 h of Ang II exposure. Ang II induced an increase of α1D-AR at short times, and BMY-7378 protected α1D-AR from desensitization.

Association between renin-angiotensin system inhibitor and the risk of CMV pneumonia:a Mendelian randomization study

Background:Cytomegalovirus(CMV)reactivation is linked to a high mortality rate,especially among the elderly.Prior research suggests that renin-angiotensin system(RAS)inhibitors may influence both the onset and prognosis of pneumonia.This study aims to examine the causal relationship between RAS inhibitor use and the risk of CMV pneumonia using Mendelian randomization(MR)analysis.Methods:We conducted an analysis using data from two genome-wide association studies(GWAS)involving individuals of European ancestry.This dataset included individuals treated with RAS inhibitors and those with CMV pneumonia.We assessed the relationship between RAS inhibitor use and CMV pneumonia risk using the inverse variance weighted(IVW)method.The results were further evaluated for pleiotropy,heterogeneity,and robustness.Results:The Mendelian randomization(MR)analysis revealed a causal relationship between RAS inhibitor use and an increased risk of CMV pneumonia(IVW:odds ratio[OR]=2.73;95%confidence interval[CI]=1.11-6.73;P=0.028).Conclusions:Our finding indicate a positive causal relationship between the use of RAS inhibitors and the onset of CMV pneumonia.

黄芪减轻血管紧张素Ⅱ诱导的小鼠血管重塑

目的探讨黄芪对血管紧张素Ⅱ(AngⅡ)诱导的血管重塑的作用及其可能机制。方法将小鼠随机分为对照组、AngⅡ组、AngⅡ+氯沙坦治疗组及AngⅡ+黄芪治疗组,每组各10只。对照组给予0.9%氯化钠注射液0.2 m L/d灌胃,其余3组均皮下埋微渗透泵,以200 ng/(kg·min)的剂量缓慢释放AngⅡ建立血管重塑模型。其中氯沙坦治疗组以10 mg/(kg·d)剂量灌胃,黄芪治疗组以20 g/(kg·d)剂量灌胃。所有小鼠总计处理14 d。每2天以尾套法测定收缩压。第14天时处死小鼠,收集主动脉进行HE及Masson染色检测血管重塑情况。RT-PCR检测主动脉Ⅰ型胶原蛋白转录水平。Western blot检测血管紧张素转换酶2(ACE2)及AngⅡ1型受体(AT1R)蛋白表达。结果黄芪处理可以显著降低AngⅡ引起的血压升高(P<0.05)、减轻AngⅡ引起的主动脉管壁增厚和纤维化增加,降低Ⅰ型胶原蛋白mRNA表达(P<0.05),上调ACE2蛋白表达(P<0.05)并下调AT1R蛋白表达(P<0.05)。结论黄芪可减轻AngⅡ诱导的血管重塑,其机制可能是通过上调ACE2和下调AT1R发挥作用。

经皮肾去交感神经术治疗老年难治性高血压患者的临床研究

目的对老年难治性高血压患者行经皮肾去交感神经术(RSD),观察其有效性、安全性及可行性。方法选择连续难治性老年高血压患者20例,行经皮RSD,观察术前和术后1、3、6个月随访时的诊室血压变化;术前和术后动态血压、血清肌酐、估算的肾小球滤过率、肾素活性、血管紧张素Ⅱ和醛固酮变化;手术并发症发生情况。结果与RSD前比较,患者RSD后1、3、6个月随访时诊室血压分别下降了16.9/11.9、24.8/17.1、29.1/20.5mm Hg(1mm Hg=0.133kPa,P<0.01),术后动态血压下降了24.2/17.2mm Hg(P<0.01),肌酐和估算的肾小球滤过率无显著变化(P>0.05),肾素活性、血管紧张素Ⅱ和醛固酮显著下降(P<0.05);1例患者发生股动脉血肿。结论对老年高血压患者行经皮RSD可能安全、有效、可行。

Protective effects of icariin on human umbilical vein endothelial cell injured by angiotensin Ⅱ

To investigate the effects of icariin （ICA） on angiotensin Ⅱ（Ang Ⅱ）-induced injury in human umbilical vein endothelial cells line （ECV-304）. The ECV-304 cells were cultured in vitro. After 24 h incubating with icariin, the model of AngⅡ-induced injury in ECV-304 was established. The cell viability （MTT method）, Lactate dehydrogenase （LDH） release and Nitric oxide （NO） production in the medium, the capacity of scavenging superoxide anion radicals （O2^-） and hydroxyl radicals （.OH） were measured. The activities of superoxide dismutase （SOD）, total nitric oxide synthase （T-NOS）, inducible nitric oxide synthase （iNOS） and constitutive nitric oxide synthase （cNOS） in the cells were determined. Compared with the Ang Ⅱ-treated group, ICA can significantly raise the viability of EC, increase the activities of SOD, T-NOS and cNOS, increase the production of NO, enhance the capacity of scavenging superoxide anion radicals （ O2^- ） and hydroxyl radicals（.OH）, and lower LDH leakage and iNOS activity. The results suggest that ICA can protect endothelial cells （ECV-304） from Ang II-induced injury.

补肾活血法对单纯收缩期高血压大鼠NO、AngⅡ的影响

目的:探讨补肾活血法对单纯收缩期高血压(Isolated Systolic Hypertension,ISH)模型大鼠血管重塑的影响。方法:采用法华林和维生素K诱导动脉中层钙化法(WVK)法复制ISH大鼠模型,分为补肾活血汤组、氨氯地平组、补肾活血汤与氨氯地平联用组(两药联用组)、空白对照组、模型对照组,予以相应的药物干预,8周后检测大鼠尾端血压、血清一氧化氮(Nitrogen Monoxide,NO)、血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)水平。结果:补肾活血法能够增加ISH大鼠血清NO水平,降低AngⅡ水平,较模型组均有统计学意义(P<0.05),且中西药联用组效果更明显。结论:补肾活血法等够改善ISH大鼠的血管顺应性。

依普沙坦治疗高血压的临床研究进展

依普沙坦是一种高选择性的血管紧张素Ⅱ-1型（AT1）受体拮抗剂.单次口服后达峰时间（tmax）为1～2.5 h,血浆蛋白质结合率高达98％;多次口服600mg/d,消除半衰期（t12）为20 h,平均稳态分布容积（Vss）为308 L.随机、双盲、多中心临床试验结果表明,依普沙坦的降压效果与依那普利、尼群地平、缬沙坦和替米沙坦相似,对收缩压的降低作用强于氯沙坦;对高血压病人的卒中二级预防作用优于尼群地平,而且依普沙坦对年龄≥50岁的新诊断为高血压的病人,在降压的同时还可适当改善他们的认知功能.病人对依普沙坦的耐受性较好,持续干咳的发生率明显低于依那普利.

复方黄芪首乌合剂对MS大鼠AngⅡ、FFA分泌及氧化应激反应的作用

目的:探讨复方黄芪首乌合剂(HQSW)对实验性代谢综合征(MS)大鼠肾组织血管紧张素Ⅱ(AngⅡ)和游离脂肪酸(FFA)分泌及氧化应激反应的影响。方法:采用高糖高脂饲料喂养建立实验性MS大鼠模型,以HQSW(低剂量组、中剂量组和高剂量组)灌胃治疗8周后,测定实验鼠血浆和肾皮质中FFA和AngⅡ浓度,以及丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果:MS大鼠血浆和肾组织SOD活力显著下降(P<0.01),而MDA、FFA和AngⅡ水平显著上升(P<0.01)。经中药HQSW干预后,血浆和肾组织SOD活力显著上升(P<0.05);同时MDA、FFA和AngⅡ水平显著下降(P<0.05)。结论:MS大鼠FFA和AngⅡ的分泌异常增多,伴有氧化应激反应异常,经HQSW的干预,上述异常状况得到改善,可能是其防治MS大鼠肾损伤的关键机制之一。

MiR-30a在血管紧张素Ⅱ诱导的心肌肥厚中的作用

目的 探讨miR-30a是否介导了血管紧张素Ⅱ（AngⅡ）诱导的心肌肥厚.方法 将心肌细胞分为对照组和AngⅡ诱导组,用Real-time PCR观察AngⅡ刺激后心肌细胞miR-30a的变化和肥厚基因的表达.将心肌细胞分为对照组和AngⅡ诱导组,用激光共聚焦观察AngⅡ刺激后心肌细胞大小的变化.将心肌细胞分为对照组（AngⅡ＋NC）、miR-30a诱导组（AngⅡ＋miR-30a mimics）和miR-30a抑制组（AngⅡ＋miR-30ainhibitors）,通过对miR-30a过表达或者抑制miR-30a活性后,观察心肌细胞肥厚基因表达和心肌细胞大小的变化.结果 AngⅡ刺激心肌细胞后,心肌细胞miR-30a表达量下调至刺激前的32.9％.AngⅡ＋miR-30amimics组心肌细胞肥厚基因ANP和β-MHC表达分别是negative control组的51.7％和53.5％,AngⅡ＋miR30a inhibitors组心肌细胞肥厚基因ANP和β-MHC表达分别是AngⅡ＋negative control组的1.88倍和1.64倍.激光共聚焦检测形态学的改变,AngⅡ刺激心肌细胞使心肌细胞面积增加至刺激前的2.95倍.与negative control组比较,AngⅡ＋miR-30a mimics组心肌细胞面积减少至57.8％,AngⅡ＋miR-30a inhibitors组心肌细胞面积增加至1.50倍.结论 miR-30a下调可介导AngⅡ诱导的心肌肥厚.

肿瘤坏死因子α增强主动脉环收缩在感染性休克中的机制研究

目的探讨肿瘤坏死因子α(TNF-α)对去内皮主动脉环反应性及主动脉血管平滑肌细胞(VSMC)内游离钙离子浓度([Ca2+]i)的影响,以证明TNF-α通过1,4,5-三磷酸肌醇受体(IP3Rs)增强VSMC对缩血管物质反应性是感染性休克早期维持血压稳定的重要机制。方法选取雄性Wistar大鼠24只制备离体去内皮主动脉环,随机分为去内皮对照组、去内皮TNF-α组、去内皮无钙对照组和去内皮无钙TNF-α组,各6只,给予血管紧张素Ⅱ(AngⅡ)刺激观察主动脉环收缩幅度。另选取3只Wistar大鼠分离鉴定原代VSMC,分为对照组和TNF-α组;另设上述2组于加AngⅡ前10 min加入IP3Rs阻断剂2-氨基乙氧基联苯硼酸盐(2-APB),即2-APB拮抗对照组和2-APB拮抗TNF-α组,观察在AngⅡ刺激后VSMC内[Ca2+]i的变化及阻断情况。结果有钙条件下,去内皮TNF-α组给予AngⅡ后主动脉环的收缩幅度高于去内皮对照组(P<0.05);无钙条件下,去内皮无钙TNF-α组给予AngⅡ后主动脉环的收缩幅度亦高于去内皮无钙对照组(P<0.05)。AngⅡ刺激可使VSMC内[Ca2+]i在短时间内迅速增加,TNF-α组[Ca2+]i升高值高于对照组、2-APB拮抗对照组和2-APB拮抗TNF-α组〔(1 315.1±496.4)与(411.6±80.3)、(13.1±9.8)、(18.7±11.9),P<0.05〕;而2-APB拮抗对照组、2-APB拮抗TNF-α组对AngⅡ刺激均失去反应,两组VSMC内[Ca2+]i间无差异(P>0.05)。结论 TNF-α可增加AngⅡ刺激VSMC引起的[Ca2+]i上升,进而引起去内皮主动脉环对AngⅡ反应性增强;证明TNF-α是通过IP3Rs通路产生效应的,这可能是感染性休克早期机体维持血压稳定的机制之一。