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.

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.

Renin-angiotensin system in the pathogenesis of liver fibrosis

Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem. In spite of many studies regarding the development of fibrosis, the understanding of the pathogenesis remains obscure. The hepatic tissue remodeling process is highly complex, resulting from the balance between collagen degradation and synthesis. Among the many mediators that take part in this process, the components of the Renin angiotensin system （RAS） have progressively assumed an important role. Angiotensin （Ang） II acts as a profibrotic mediator and Ang-（1-7）, the newly recognized RAS component, appears to exert a counter-regulatory role in liver tissue. We briefly review the liver fibrosis process and current aspects of the RAS. This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis, focusing on the putative role of the ACE2-Ang-（1-7）- Mas receptor axis.

Relationship between angiotensin-(1-7) and angiotensin Ⅱ correlates with hemodynamic changes in human liver cirrhosis

AIM： To measure circulating angiotensins at different stages of human cirrhosis and to further evaluate a possible relationship between renin angiotensin system （RAS） components and hemodynamic changes. METHODS： Patients were allocated into 4 groups： mild-to-moderate liver disease （MLD）, advanced liver disease （ALD）, patients undergoing liver transplantation, and healthy controls. Blood was collected to determine plasma renin activity （PRA）, angiotensin （Ang） Ⅰ, Ang Ⅱ, and Ang-（1-7） levels using radioimmunoassays. During liver transplantation, hemodynamic parameters were determined and blood was simultaneously obtained from the portal vein and radial artery in order to measure RAS components. RESULTS： PRA and angiotensins were elevated in ALD when compared to MLD and controls （P 〈 0.05）. In contrast, Ang Ⅱ was significantly reduced in MLD. Ang-（1-7）/Ang Ⅱ ratios were increased in MLD when compared to controls and ALD. During transplantation, Ang Ⅱ levels were lower and Ang-（1-7）/Ang Ⅱ ratios were higher in the splanchnic circulation than in the peripheral circulation （0.52 ± 0.08 vs 0.38 ±0.04, P 〈 0.02）, whereas the peripheral circulating Ang Ⅱ/Ang Ⅰ ratio was elevated in comparison to splanchnic levels （0.18 ±0.02 vs 0.13 ±0.02, P 〈 0.04）. Ang-（1-7）/ Ang Ⅱ ratios positively correlated with cardiac output （r = 0.66） and negatively correlated with systemic vascular resistance （r = -0.70）. CONCLUSION： Our findings suggest that the relationship between Ang-（1-7） and Ang Ⅱ may play a role in the hemodynamic changes of human cirrhosis.

Effects on Cell Viability and on Apoptosis in Tumoral(MCF-7)and in Normal(MCF10A)Epithelial Breast Cells after Human Chorionic Gonadotropin and Derivated-Angiotensin Peptides Treatments

Angiotensin-(1 - 7) [Ang-(1 - 7)] is an endogenous heptapeptide hormone of the renin-angiotensin system that has antiproliferative properties. The aim of this work was to evaluate the anti-proliferative and pro-apoptotic properties of Ang-(1 - 7) and of Ang-(1 - 7)-substituents 9-fluorenylmethyloxycarbonyl (Fmoc) e Ang II-derivatives containing the TOAC (2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid) in normal (MCF10A) and in tumoral (MCF7) epithelial mammary cell lines. Both cell lines received an hCG and angiotensin peptides 24-hour treatment, in combination or alone followed by cell viability, apoptosis and cell cycle assays performed by flow cytometer (GUAVA). After hCG, Ang-(1 - 7), hCG + Ang-(1 - 7) and hCG + Ang-(1 - 7)-Fmoc treatments, MCF7 displayed cell viability decrease and mid-apoptosis increase. We also observed cell viability decrease in MCF10A after Ang-(1 - 7), Ang-(1 - 7) Fmoc and hCG + AngII Toac treatments. These cells had an increase in late apoptosis and necrosis after AngII Toac, hCG + Ang-(1 - 7) and hCG + Ang-(1 - 7)-Fmoc treatments. Regarding the cell cycle analysis, we did not observed any changes in cell cycle phases. In summary, cell viability was decreased and apoptosis (initial, mid and late) was increased after hCG and/or Ang-(1 - 7) peptides treatments. These results point out hCG and Ang-(1 - 7) as effective compounds to inhibit cell proliferation, since they decrease cell viability and increase apoptosis in both normal and in tumoral breast cells, being the effect more pronounced in the tumoral cell line. Our results support the idea of investigating more closely the putative use of these compounds as novel therapeutic agents for breast cancer.

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.

Renin-angiotensin system blockade: Effect on renal mRNA expression in 5/6 nephrectomized rats

The aim of this study was to determinate the gene expression levels of angiotensinogen, angiotensin converting enzyme, renin, (pro)renin receptor, and the final rennin-angiotensin system (RAS) products Angiotensin (Ang) II and Ang 1-7 inthe remnant kidney of 5/6 nephrectomized rats and its response to RAS pharmacological blockade. Male Wistar rats were divided into five groups: sham operated (SO), 5/6 nephrectomized (NFX), NFX + captopril (50 mg/ kg/day), NFX + losartan (10 mg/kg/day), and NFX + aliskiren (10 mg/kg/day). Animals were followed up for 60 days and protein urine excretion was measured. Systolic blood pressure, renal tissue RAS mRNA expression levels, plasma Ang II, and plasma Ang 1-7 were evaluated at day 60 after nephrectomy. Blood pressure and urine protein were increased after 5/6 nephrectomy. Ang II levels were increased 9.4 fold, whereas Ang 1-7 decreased 72.9% in NFX animals compared with SO rats. 5/6 nephrectomy increased renal angiotensinogen and (pro)renin receptor mRNA expression but down-regulated renin mRNA expression. RAS blockade restored the systolic blood pressure to normal values and slowed down urinary protein excretion, and also prevented changes in Ang II and Ang 1-7. RAS blockade reduced (pro)renin receptor, ACE, and AGT mRNA expression in the remnant kidney. However, renin mRNA expression increased compared with NFX rats. In conclusion these results suggest that inhibition of Ang II synthesis by RAS blockade is associated with renal regulation of RAS mRNA expression and this may be through a mechanism related with the Ang II/Ang 1-7 balance.

Ocular renin-angiotensin system with special reference in the anterior part of the eye

The renin-angiotensin system(RAS) regulates blood pressure(BP) homeostasis, systemic fluid volume and electrolyte balance. The RAS cascade includes over twenty peptidases, close to twenty angiotensin peptides and at least six receptors. Out of these, angiotensin Ⅱ, angiotensin converting enzyme 1 and angiotensin Ⅱ type 1 receptor(AngⅡ-ACE1-AT1R) together with angiotensin(1-7), angiotensin converting enzyme 2 and Mas receptor(Ang(1-7)-ACE2-Mas R) are regarded as the main components of RAS. In addition to circulating RAS, local RA-system exists in various organs. Local RA-systems are regarded as tissue-specific regulatory system accounting for local effects and long term changes in different organs. Many of the central components such as the two main axes of RAS: AngⅡ-ACE1-AT1 R and Ang(1-7)-ACE2-Mas R, have been identified in the human eye. Furthermore, it has been shown that systemic antihypertensive RAS- inhibiting medications lower intraocular pressure(IOP). These findings suggest the crucial role of RAS not only in the regulation of BP but also in the regulation of IOP, and RAS potentially plays a role in the development of glaucoma and antiglaucomatous drugs.

The Role for AVE0991 (MAS-Receptor Angiotensin II (1-7) Agonist) in Reducing Cisplatin-Induced Acute Kidney Injury on C57BL/6 Mice

Acute Kidney Injury (AKI) is a condition that causes nephrotoxicity in kidney tissues due to cisplatin-induced cancer treatments. Hence, it is proposed in this review that AVE0991 (a MAS-receptor Angiotensin II (1-7) agonist) may reduce cisplatin-induced acute kidney injury by promoting nitric oxide production.

A Study of the Correlation between Angiotensin (1-7) and the Histopathological Changes in the Penises of Experimentally Diabetic Rats

Background: Diabetes mellitus is an important risk factor for erectile dysfunction. Renin-angiotensin system with its branches Angiotensin II and Angiotensin 1-7 [Ang-(1-7)] are altered in diabetes and could affect erection. So, in this study we determine the level of Ang-(1-7), nitrite (the major nitric oxide metabolite) and histopathological changes in penile tissues of type I diabetic rats. A total of 60 male albino rats were divided into two groups: group I (control) and group II (diabetic) for either 4 weeks in group IIa, or 8 weeks in group IIb. Diabetes was induced by intraperitoneal injection of streptozotocin (60 mg/kg). Penile levels of Ang-(1-7), nitrite and histopathological examination were assessed at 4 and 8 weeks after diabetes induction. Results: Ang-(1-7) and nitrite were decreased in diabetic rats at 4 weeks and continued to be lower at 8 weeks for Ang-(1-7) only. Loss of corpus cavernosum smooth muscle was present in 25% and 85% of rats at 4 and 8 weeks of diabetes respectively (P Conclusion: Diabetes induced progressive decrease in the release of Ang-(1-7) and nitric oxide from the corpora cavernosa in a time-dependent manner with concomitant fibro-muscular changes that end by corporal fibrosis affecting subsequently erectile functions.

Advances in angiotensin-(1-7) and atrial fibrillation

Atrial fibrillation (AF) is one of the most common arrhythmias in clinic. Atrial fibrillation and its complications are one of the important causes of death. Despite the development of new therapies, including catheter ablation, the treatment of atrial fibrillation remains an important and arduous task. Current studies on the mechanism of atrial fibrillation show that the occurrence and development of atrial fibrillation mainly involves the electrophysiological mechanism of the heart and the pathophysiological mechanism of the heart. Atrial remodeling plays an important role in the process of atrial fibrillation. Atrial remodeling includes electrical remodeling of atrial structure. The early stage of atrial remodeling is characterized by electrophysiological and ion channel changes, while the late stage is characterized by amyloidosis and fibrosis of extracellular matrix and atrial muscle. Angiotensin-converting enzyme 2 and angiotensin-(1-7) are important components of renin-angiotensin-aldosterone system. Recent studies have shown that angiotensin - (1-7) plays an important protective role in the occurrence and development of atrial fibrillation. In this paper, the relationship between angiotensin - (1-7) and atrial remodeling during atrial fibrillation and its research progress are reviewed.

Effect of angiotensin 1-7 on endothelial cell injury caused by oxidative stress

Objective:To study the effects of angiotensin 1-7 (Ang1-7) on endothelial cell injury caused by oxidative stress.Methods: Human umbilical vein endothelial cells (HUVECs) were cultured and divided into blank control group, hydrogen peroxide and different Ang1-7 dose groups (1, 2 and 4 μmol/L Ang1-7 groups). The cell proliferation activity, the contents of antioxidant enzymes in cell culture medium, and the contents of endoplasmic reticulum stress molecules in cells were determined.Results: After 6, 12, 18 and 24 h of treatment, CCK-8 proliferation activity values of hydrogen peroxide group were significantly lower than those of blank control group, CCK-8 proliferation activity values of 1, 2 and 4 μmol/L Ang1-7 groups were significantly higher than those of hydrogen peroxide group, and the larger the Ang1-7 dose, the higher the CCK-8 proliferation activity values;after 24 h of treatment, SOD, GSH-Px, HO-1 and CAT contents in cell culture medium of hydrogen peroxide group were significantly lower than those of control group, and GRP78, XBP1 and CHOP contents in cells were significantly higher than those of control group;SOD, GSH-Px, HO-1 and CAT contents in cell culture medium of 1, 2 and 4 μmol/L Ang1-7 groups were significantly higher than those of hydrogen peroxide group, GRP78, XBP1 and CHOP contents in cells were significantly lower than those of hydrogen peroxide group, and the larger the Ang1-7 dose, the more significant the changes of above molecules in cell culture medium and cells.Conclusion: Angiotensin 1-7 has protective effect on the endothelial cell injury caused by oxidative stress.

Effects of Angiotensin Ⅱ and ACE Inhibitor,Captopril on L-type Calcium Current and Sodium Current of Single Guinea Myocytes

Objectives To investigate effect of Angll, captopril on single guinea myocytes on L - type calcium current and sodium current. Methods Membrane patch clamp whole cell recording technique was used to investigate effect of angll, captopril on L - Ca maximum current density and sodium maximum current density. Resutls Angll increased the maximum current density compared with control after perfused 5 min, 357. 7 ±219. 7 Vs 279. 5± 240. 5 PA/PF, increase rate is 27. 9 %, the shape of current - voltage relationship curve was unchanged, peaked at + 10 mv, indicated that angll increased L - Ca current density in voltage - dependent. After perfused with captopril, captopril + angll 3, 5 min, L - Ca current was recorded, results suggest L - Ca maximum current density decreased significantly compared with control, in captopril group, 128. 4 ± 92. 6Vs286. 2 ± 89. 7, 66. 7±68. 3Vs 286. 2 ± 89. 7, respectively, rate of inhibition is 55. 1 %, 76. 6 %, respectively. L - Ca current further decreased in captopril perfused 5 min compared with 3 min, 66. 7 ± 68. 3 Vs 128. 4 ± 92. 6, in captopril + angll group, L - Ca current decreased greatly in 3, 5 min than control, 143. 4±117. 6Vs 267. 7±141. 4, 96. 4±82. 5 Vs 267. 7±141. 4, respectively, rate of inhibition is 46. 4 % , 63. 9 % respectively. We also investigated effect of captopril on Na current, which decreased significantly in 1 min and 3 min compared with control, 939. 1 ±319. 1 Vs 1398. 0±144. 6 PA/PF, 469. 95 ± 314. 9 Vs 1398. 0 ±144. 6 PA/PF, respectively, rate of inhibition is 32. 8 % , 66. 3 % , respectively. Na current density decreased significantly in 3 min compared with 1 min, 469. 9±314. 9 Vs 939. 1±319. 1PA/PF, rate of inhibition is 49. 9 % . Conclusions Angiotensin Ⅱexerts increased maximum current density of L - Ca in voltage dependent, captopril decreased maximum current density of L - Ca in voltage dependent, decreased sodium maximum current density, which is the prominently antiarrhythmia mechanisms through inhibition of angiotensin Ⅱ evoked calcium dependent transient inward current and calcium overload.

白芍总苷对代谢综合征-高血压大鼠改善胰岛素敏感性、降压和抗氧化作用

目的:探讨白芍总苷(TGP)对代谢综合征-高血压(metabolic syndromic-hypertension,MS-Ht)大鼠血压的作用,检测胰岛素敏感性、细胞因子、血管活性物质以及氧化应激的改变,研究其作用机制。方法:采用高脂、高糖饮食喂饲SD大鼠,连续8周,当造模动物出现高血压、糖耐量减退,MS-Ht病理模型建立成功;然后将大鼠随机分为模型对照、二甲双胍(metformin,Met)200 mg/kg和TGP 150、50 mg/kg两个剂量组;分别灌胃给药或蒸馏水,qd×4周,实验结束时,测定大鼠血压、空腹血糖(FBG)和口服糖耐量试验2 h血糖(OGTT-2 hBG)、血浆胰岛素(Fins),并计算胰岛素敏感性(ISI)和胰岛素抵抗指数(HOMA-IRI);测定游离脂肪酸(FFA)、TNF-α、内皮素(ET-1)、肾素-血管紧张素(AngⅡ)、NO和丙二醛(MDA)含量以及一氧化氮合酶(NOS)和超氧化物歧化酶(SOD)活性。结果:与正常对照组比较,MS-Ht大鼠血压升高;FBG、OGTT-2hBG和Fins含量增高;ISI减弱、而HOMA-IRI增强;FFA、TNF-α、ET-1、肾素-AngⅡ和MDA含量增高(P<0.05或P<0.01);NO含量和NOS及SOD活性降低(P<0.05或P<0.01)。Met和TGP 150 mg/kg增强ISI,而降低HO-MA-IRI,纠正高胰岛素血症(P<0.05或P<0.01),降低FFA、TNF-α、ET-1、肾素-AngⅡ和MDA含量(P<0.05或P<0.01),提高NO含量和NOS及SOD活性;而Met能降低FBG、OG-TT-2 h BG含量(P<0.05或P<0.01);与TGP150 mg/kg组比较,差异无统计学意义(P>0.05);TGP 50 mg/kg组,除降低肾素、AngⅡ和FFA含量外(P<0.05),对其余指标,差异均无统计学意义(P>0.05)。结论:TGP和Met能对抗MS-Ht大鼠胰岛素抵抗、增强胰岛素敏感性、纠正高胰岛素血症,拮抗ET-1、肾素-AngⅡ系统和氧化应激反应,提高NO和NOS功能,降低血压;TGP不具直接降血糖作用,与Met不同。TGP以上效应呈量效关系。

丙泊酚或异氟醚麻醉对肾素-血管紧张素系统的影响

目的比较丙泊酚靶控输注(TCI)或异氟醚吸入麻醉对肾素-血管紧张素系统(RAS)和血流动力学的影响。方法择期行胃切除手术的患者30例,ASA Ⅰ或Ⅱ级,随机分成丙泊酚TCI组(Ⅰ组)和异氟醚吸入麻醉组(Ⅱ组),每组15例。丙泊酚、芬太尼诱导后,Ⅰ组丙泊酚TCI维持麻醉,Ⅱ组异氟醚、氧化亚氮低流量吸入维持麻醉。麻醉中以听觉诱发电位(AEP)和脑电双频指数(BIS)作为麻醉深度指标,记录麻醉前(T1)、诱导插管后5min(T2)、切皮(T3)、探查(T4)、术毕拔管后5min(T5)时BP、HR、AEP、BIS、血浆肾素活性(PRA)和血管紧张素Ⅱ(AngⅡ)值。结果与T1时比较,T2时两组PRA、AngⅡ和BP均显著下降(P<0.01),T3、T4时Ⅰ组PRA显著下降,而Ⅱ组AngⅡ显著增高(P<0.01)。T3、T4时Ⅱ组PRA均显著高于Ⅰ组(P<0.01),T3、T4和T5时Ⅱ组AngⅡ显著高于Ⅰ组(P<0.05)。T4时Ⅱ组BP和HR显著高于T1时(P<0.05)。T5时Ⅰ组BIS显著低于Ⅱ组(P<0.05)。结论丙泊酚TCI可抑制RAS,应激反应轻,优于异氟醚吸入麻醉。

复方孕二烯酮与二甲双胍联合应用对PCOS患者IGF-1、IGFBP-1、 肾素-血管紧张素系统及促排卵结局的影响

目的:研究二甲双胍与复方孕二烯酮(复方GES)对多囊卵巢综合征(PCOS)患者卵巢肾素-血管紧张素系统(RAS)、血清胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-1(IGFBP-1)、性激素水平及促排卵结局的影响并探讨其可能的作用机制。方法:选择PCOS患者40例,随机分为两组,实验组接受二甲双胍及复方GES治疗,连续3个月。治疗前后分别测定血浆肾素原(PRA)、血管紧张素Ⅱ(ATⅡ)及血清IGF-1、IGFBP-1、空腹胰岛素(INS)、空腹血糖(GLU)、黄体生成素(LH)、促卵泡素(FSH)、雄烯二酮(A2)、雌二醇(E2)、睾酮(T),测量每侧卵巢内卵泡数目、卵巢体积并观察临床症状的改善及服药期间的副反应。停药后开始促排卵治疗。对照组直接进行促排卵治疗。结果:实验组服药3个周期后,FSH(P<0.05)、LH、A2、E2、T水平及LH/FSH比值(P<0.01)均显著下降,血浆PRA、ATⅡ与空腹INS、BMI、INS/GLU比值显著降低(P<0.01)。IGFBP-1水平明显上升(P<0.05)。超声监测双侧卵巢体积显著缩小,卵泡数目明显减少(P<0.01)。促排卵治疗过程中,实验组HMG(或FSH)用量显著低于对照组(P<0.01),单卵泡生长率和HCG日A型内膜出现率均高于对照组(P<0.01),周期排卵率显著高于对照组(P<0.05)。结论:二甲双胍与复方GES合并用于PCOS患者,能改善PCOS患者内分泌水平,调节PCOS患者IR状态,显著提高PCOS患者CC+HMG方案促排卵治疗的效果,并减少促排卵并发症的发生。

高氧致慢性肺疾病新生大鼠肺组织肾素-血管紧张素系统和TGF-β1的动态变化及卡托普利的干预机制

目的观察高氧致慢性肺疾病(CLD)新生大鼠肺组织血管紧张素转换酶(ACE)、血管紧张素Ⅱ(AngⅡ)、转化生长因子β1(TGF-β1)的动态变化及卡托普利的保护机制。方法足月新生 Wistar 大鼠 240 只,随机分为 4 组,每组 60 只。模型组、盐水对照组及卡托普利治疗组将足月新生 Wistar 大鼠(连同母鼠)置于氧舱内持续吸入高浓度氧(FiO2∶0.9)21 d 造成高氧肺损伤模型,空气对照组吸入空气;卡托普利治疗组于生后 7 d 起经胃管灌服卡托普利 30 mg·kg-·1d-1,盐水对照组每天经胃管灌服等量生理盐水。每组分别于实验开始后的第 1,3,7,14,21 d 随机各选取 6 只麻醉后处死。采用酶联免疫吸附法测定肺组织 TGF-β1 的含量,用日产 7170 全自动生化分析仪测定 ACE 活性,用放免法测定 Ang Ⅱ的含量。采用 RT-PCR 检测肺组织 ACE、AngⅡ、TGF-β1 mRNA 表达的动态变化并同时观察肺组织形态学变化。结果 4 组肺组织 ACE、AngⅡ和 TGF-β1 的含量及 mRNA 表达在实验后 1,3,7 d 差异无统计学意义(P > 0.05);模型组、盐水对照组 14 d 明显升高,21 d 达高峰,与空气对照组比较差异显著(P < 0.05 或 0.01);卡托普利治疗组 14 和 21 d 与模型组、盐水对照组比较明显降低(P < 0.05 或 0.01),但仍高于空气对照组(P < 0.05)。模型组、盐水对照组实验后 1d 肺组织形态学同空气对照组,14 d 出现肺组织纤维化改变,21 d 出现严重纤维化。卡托普利治疗组肺组织纤维化病变明显减轻。结论高氧致 CLD 新生大鼠肺组织 ACE、AngⅡ、TGF-β1 含量及 mRNA 表达在高氧后 14 和 21 d 明显增高,同时肺组织出现纤维化改变,应用卡托普利干预后上述指标明显低于模型组及盐水对照组,肺纤维化病变明显减轻,表明卡托普利对高氧肺损伤具有一定的保护作用。

肾素-血管紧张素系统与心房颤动关系研究的可视化分析

目的运用Citespace软件对肾素-血管紧张素系统与心房颤动(房颤)关系的相关研究规律以可视化知识图谱的形式进行展示,以揭示该领域的研究方向、研究热点和研究前沿。方法以Web of Science核心合集数据库为数据来源,利用可视化分析软件Citespace5.4 R3对肾素血管紧张素系统与房颤关系相关研究进行可视化分析,探讨相关研究的文献分布、国家/机构分布、作者分布以及对共被引文献和关键词进行分析。结果共纳入503篇SCI文章,年度发文量和引文量总体呈现上升趋势;美国、中国、意大利、德国和日本为该领域研究的主要国家,加拿大蒙特利尔大学是该领域发文量最多的机构;发文量最高的作者是台湾大学的LIN JL及TSAI CT。主要的研究热点为房颤合并心力衰竭、心肌梗死研究,血管紧张素转化酶抑制剂或血管紧张素受体阻滞剂治疗房颤等研究。氧化应激在房颤发生中的作用,肾素血管紧张素抑制剂对心力衰竭、慢性肾病合并房颤的治疗作用,房颤的上游治疗药物的研究是肾素血管紧张素系统与房颤关系相关研究的前沿领域。结论本研究运用Citespace软件对肾素血管紧张素系统与房颤关系的相关研究规律以可视化知识图谱的形式进行展示,揭示该领域的研究方向、研究热点和研究前沿,为研究人员进一步的研究提供指引与参考。

ACE2/Ang-(1-7)改善肝细胞糖代谢

目的肾素-血管紧张素系统(rennin-angiotensin system,RAS)参与糖代谢。血管紧张素转换酶2(angiotensin converting enzyme 2,ACE2)-血管紧张素(1-7)〔Ang-(1-7)〕-Ang-(1-7)受体(MAS)是新发现的RAS调节轴,可拮抗经典轴的生物效应。本文研究ACE2/Ang-(1-7)在肝脏糖代谢中的作用。方法 1利用Ang-(1-7)及MAS拮抗剂(A779)干预Hep G2细胞,或ACE2过表达载体转染人肝细胞株Hep G2;2实时荧光定量PCR(real-time PCR,RT-PCR)检测糖代谢相关基因和氧化应激相关基因表达;3流式细胞仪检测活性氧(reactive oxygen species,ROS)浓度;4蛋白质印迹(Western blotting)法检测还原型辅酶II(NADPH)相关亚基的表达。结果 1 ACE2过表达细胞中,糖异生相关基因磷酸烯醇式丙酮酸羧激酶(phosphoenolpyruvate carboxykinase,PEPCK)的表达水平显著降低,而葡萄糖-6-磷酸激酶(glucose-6-phosphatase,G6Pase)与对照组相比差异无统计学意义;2葡萄糖转运蛋白2(glucose transporter type 2,Glut2)、胰岛素受体底物2(insulin receptor substrate,IRS-2)和腺苷酸活化蛋白激酶α亚基2〔adenosine 5’-monophosphate(AMP)-activated protein kinase,AMPKα2〕的表达水平显著增高,而细胞因子信号抑制因子-3(suppressor of cytokine signaling-3,SOCS-3)与对照组相比,表达量显著降低;3 Ang-(1-7)降低Hep G2细胞内和细胞外ROS的浓度;4 Ang-(1-7)降低NADPH亚基p67和p22的表达;ACE2过表达,也能显著降低Hep G2细胞中p22和p47的表达,同时,ACE2对氧化应激的保护作用能被A779抑制。结论 ACE2改善肝脏糖代谢,其机制可能与ACE2/Ang-(1-7)对肝脏氧化应激的保护作用有关。

肾素-血管紧张素系统基因与妊娠高血压综合征的新进展

肾素-血管紧张素-醛固酮系统(renin-angiotensin system,RAS)基因是一种激素内分泌系统,在心血管功能调节、水盐平衡调节中起重要作用。RAS基因是妊高征主要的致病基因。AGT基因M235T多态、AT1R基因A1166C多态、ACE基因I/D缺失多态与妊高征的发病相关。