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Tanshinone IIA ameliorates myocardial ischemia/reperfusion injury in rats by regulation of NLRP3 inflammasome activation and Th17 cells differentiation. 丹参酮IIA通过调节NLRP3炎性体激活和Th17细胞分化改善大鼠心肌缺血再灌注损伤。
IF 1.1 4区 医学 Q2 Medicine Pub Date : 2022-10-28 eCollection Date: 2022-01-01 DOI: 10.1590/acb370701
Dan Li, Zhihui Yang, Shan Gao, Hao Zhang, Guanwei Fan

Purpose: Tanshinone IIA is a well-known lipophilic active constituent refined from traditional Chinese medicines, danshen. It has been previously demonstrated to possess various biological properties, including anti-inflammatory, antioxidant, promoting angiogenesis effect and so on. However, the mechanism of tanshinone IIA on myocardial ischemia-reperfusion injury (MI/RI) remains unclear. In this study, we investigated the effect of tanshinone IIA on MI/RI.

Methods: MI/RI rat models were set up. Echocardiographic evaluation and hematoxylin and eosin staining were performed to analyze the cardiac function and morphology of MI/RI. Western blot was conducted for the detection of protein expression of pyrin domain containing 3 (NLRP3) and caspase-1 in heart tissues. Flow cytometry and real-time polymerase chain reaction were used for the detection of proinflammatory cytokines and Th17 cells differentiation.

Results: We found that tanshinone IIA alleviated the myocardial damage of MI/RI, ameliorated the overall and local inflammatory reaction, and produced a cardioprotective effect by inhibiting of NLRP3 inflammasome activation and Th17/Treg cells differentiation.

Conclusions: Our results highlighted the cardio-protective effect of tanshinone IIA on MI/RI and uncovered its underlying mechanism related to the NLRP3 inflammasome inhibition and the modulation of Th17/Treg cells differentiation.

目的:丹参酮IIA是从中药丹参中提炼出来的一种著名的亲脂活性成分。它具有多种生物学特性,包括抗炎、抗氧化、促进血管生成等作用。然而,丹参酮IIA对心肌缺血再灌注损伤(MI/RI)的作用机制尚不清楚。在本研究中,我们研究了丹参酮IIA对MI/RI的影响。方法:建立心肌梗死/心肌梗死大鼠模型。超声心动图评价及苏木精和伊红染色分析心肌梗死/心肌梗死的心功能和形态学。Western blot检测心脏组织中pyrin domain containing 3 (NLRP3)和caspase-1蛋白的表达。采用流式细胞术和实时聚合酶链反应检测促炎细胞因子和Th17细胞分化情况。结果:我们发现丹参酮IIA可减轻MI/RI的心肌损伤,改善整体和局部炎症反应,并通过抑制NLRP3炎性体活化和Th17/Treg细胞分化产生心脏保护作用。结论:我们的研究结果强调了丹参酮IIA对MI/RI的心脏保护作用,并揭示了其与NLRP3炎症小体抑制和Th17/Treg细胞分化调节有关的潜在机制。
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引用次数: 3
Jatrorrhizine reduces myocardial infarction-induced apoptosis and fibrosis through inhibiting p53 and TGF-β1/Smad2/3 pathways in mice. 麻天碱通过抑制小鼠p53和TGF-β1/Smad2/3通路减少心肌梗死诱导的凋亡和纤维化。
IF 1.1 4区 医学 Q2 Medicine Pub Date : 2022-10-28 eCollection Date: 2022-01-01 DOI: 10.1590/acb370705
Mingxiu Hao, Kunli Jiao

Purpose: To explore the mechanism of jatrorrhizine on apoptosis and fibrosis induced by myocardial infarction (MI) in an animal model.

Methods: The left anterior descending branch of coronary artery was surgically ligated to duplicate the mouse model of MI. The sham and infarcted mice were treated with normal saline once a day, while mice in experimental groups received low-dose (LD) and high-dose (HD) jatrorrhizine once a day respectively. Two weeks later, cardiac function was detected by echocardiography, and histopathological examination was performed using hematoxylin and eosin (H&E) and Masson staining. The expressions of p53, TGF-β1, Smad/2/3, Bax, Bcl-2, collagen I and collagen III were quantified using qRT-PCR and western blot assays.

Results: Jatrorrhizine significantly improved left ventricular ejection fraction (LVEF) and left ventricle end-systolic (LVES) in mice. Histopathological, administration of jatrorrhizine weakened infiltration of inflammatory cells and cardiac fibrosis in myocardium of mice caused by MI. Additionally, jatrorrhizine suppressed cardiomyocyte apoptosis exhibited as its capability to reverse changes of Bax and Bcl-2 levels in myocardium caused by MI. Jatrorrhizine statistically significantly downregulated expression of collagen I and collagen III, as well as TGF-β1, Smad2/3 and p53.

Conclusions: Jatrorrhizine reduce cardiomyocyte apoptosis and fibrosis through inhibiting p53/Bax/Bcl-2 and TGF-β1/Smad2/3 signaling pathways.

目的:探讨麻风根碱对心肌梗死(MI)动物模型细胞凋亡和纤维化的作用机制。方法:手术结扎冠状动脉左前降支复制心肌梗死小鼠模型,假手术小鼠和梗死小鼠每天1次生理盐水治疗,实验组小鼠每天1次低剂量(LD)和高剂量(HD)麻根碱治疗。2周后行超声心动图检测心功能,苏木精伊红(H&E)及Masson染色行组织病理学检查。采用qRT-PCR和western blot检测细胞中p53、TGF-β1、Smad/2/3、Bax、Bcl-2、I型胶原和III型胶原的表达。结果:麻风根碱可显著提高小鼠左心室射血分数(LVEF)和左心室收缩末期分数(LVES)。病理组织学结果显示,麻疯根碱可减弱心肌炎症细胞的浸润和心肌纤维化,抑制心肌细胞凋亡,逆转心肌中Bax和Bcl-2水平的变化,显著下调I型胶原和III型胶原的表达,下调TGF-β1、Smad2/3和p53的表达。结论:麻疯根碱通过抑制p53/Bax/Bcl-2和TGF-β1/Smad2/3信号通路减少心肌细胞凋亡和纤维化。
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引用次数: 4
NLRP3 inflammasome inhibitor MCC950 can reduce the damage of pancreatic and intestinal barrier function in mice with acute pancreatitis. NLRP3炎症小体抑制剂MCC950可减轻急性胰腺炎小鼠胰腺和肠道屏障功能的损伤。
IF 1.1 4区 医学 Q2 Medicine Pub Date : 2022-10-28 DOI: 10.1590/acb370706
Yanghui Shen, Huobao Yang, Dansen Wu, Hangmei Yang, Donghuang Hong

Purpose: Abnormal activation of NOD-like receptor protein 3 (NLRP3) inflammasome can lead to the occurrence and progression of acute pancreatitis. This study investigated the protective effect of MCC950 on pancreatitis mice.

Methods: Eighteen mice were randomly divided into control group, severe acute pancreatitis (SAP) group and SAP+MCC950 group. Serum interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) were measured by ELISA. Hematoxylin and eosin (HE) staining was used to evaluate the pathological damage. Western blotting was used to detect the expression of NLRP3 inflammasome and tight junction proteins in the small intestine and pancreas.

Results: MCC950 could reduce the levels of IL-6 and IL-1β in SAP mice. After treatment with MCC950, the expression levels of NLRP3 inflammasome in the pancreas of SAP mice were significantly reduced and the pathological damage to the pancreas and intestine was alleviated. Compared with the control group, the expression of tight junction protein (ZO-1,occludin and claudin-4) in the intestinal mucosa of SAP mice was decreased, and the expression of claudin-4 and occludin were upregulated after MCC950 treatment.

Conclusions: MCC950 can inhibit NLRP3 inflammasome activation and significantly reduce the inflammatory response and delay the process of pancreatitis. It has therapeutic potential in the treatment of acute pancreatitis.

目的:NOD样受体蛋白3(NLRP3)炎症小体的异常激活可导致急性胰腺炎的发生和发展。本研究探讨了MCC950对胰腺炎小鼠的保护作用。方法:将18只小鼠随机分为对照组、重症急性胰腺炎(SAP)组和SAP+MCC950组。ELISA法测定血清白细胞介素-1β、IL-6和肿瘤坏死因子-α。苏木精-伊红(HE)染色用于评估病理损伤。Western印迹法检测NLRP3炎症小体和紧密连接蛋白在小肠和胰腺中的表达。结果:MCC950可降低SAP小鼠IL-6和IL-1β水平。用MCC950处理后,SAP小鼠胰腺中NLRP3炎症小体的表达水平显著降低,胰腺和肠道的病理损伤减轻。与对照组相比,MCC950处理后,SAP小鼠肠黏膜中紧密连接蛋白(ZO-1、occludin和claudin-4)的表达降低,claudin-3和occludin4的表达上调。结论:MCC950可抑制NLRP3炎症小体的激活,显著降低炎症反应,延缓胰腺炎的进程。它在治疗急性胰腺炎方面具有治疗潜力。
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引用次数: 1
Tranexamic acid effects in postoperative bleeding outcomes in laparoscopic sleeve gastrectomy: a controlled study. 氨甲环酸对腹腔镜袖式胃切除术术后出血的影响:一项对照研究。
IF 1.1 4区 医学 Q2 Medicine Pub Date : 2022-10-10 eCollection Date: 2022-01-01 DOI: 10.1590/acb370702
Roger Moura de Brito, Caio Márcio Barros de Oliveira, Ed Carlos Rey Moura, Giuliano Peixoto Campelo, Roclides Castro Lima, Ciro Sousa de Moura Fe, Tércio Maia Sousa, Eduardo José Silva Gomes de Oliveira, Almir Vieira Dibai Filho, Plínio da Cunha Leal

Purpose: To demonstrate through a controlled study whether the use of tranexamic acid in bariatric surgeries is effective for bleeding control.

Methods: Prospective, comparative, and double-blind study performed with patients from 18 to 65 years old submitted to bariatric surgery. The selected patients received venous tranexamic acid (TXA) during the induction of anesthesia or not (CG). The anesthesia and thromboprophylaxis protocols were similar among the groups. For statistical analysis, the χ2 and analysis of variance tests were performed at a significance level of p < 0.05, using the statistical program SPSS 21.0®.

Results: Sixty-one patients were included in the study, 31 in the control group and 30 in the TXA group (GTXA). In the intraoperative period, the bleeding volume was greater in the CG than in the GTXA. In the postoperative period, the tranexamic acid group had a higher value hematocrit, absence of surgical reoperations due to bleeding complications, and shorter hospitalization time than the control group.

Conclusions: The use of tranexamic acid was effective in reducing bleeding rates and of hospital stay length, in addition to demonstrating the clinical safety of its use, for not having been associated with any thromboembolic events.

目的:通过一项对照研究来证明在减肥手术中使用氨甲环酸是否能有效地控制出血。方法:对18 ~ 65岁接受减肥手术的患者进行前瞻性、比较和双盲研究。选择的患者在麻醉诱导或不诱导时静脉注射氨甲环酸(TXA)。各组麻醉和血栓预防方案相似。采用SPSS 21.0®统计软件进行χ2检验和方差分析,p < 0.05为显著性水平。结果:61例患者纳入研究,其中31例为对照组,30例为TXA组(GTXA)。术中CG出血量大于GTXA出血量。术后,氨甲环酸组红细胞压积值较高,无出血并发症再手术,住院时间较对照组短。结论:氨甲环酸的使用在减少出血率和住院时间方面是有效的,除了证明其使用的临床安全性外,还与任何血栓栓塞事件无关。
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引用次数: 3
Mesenchymal stem cells have ameliorative effect on the colitis model via Nrf2/HO-1 pathway. 间充质干细胞通过Nrf2/HO-1通路对结肠炎模型有改善作用。
IF 1.1 4区 医学 Q2 Medicine Pub Date : 2022-10-10 eCollection Date: 2022-01-01 DOI: 10.1590/acb370704
Mehmet Fatih Bozkurt, Muhammed Nasir Bhaya, Cengiz Dibekoğlu, Ayberk Akat, Utku Ateş, Oytun Erbaş

Purpose: To evaluate the ameliorative effect of mesenchymal stem cells (MSCs) on acetic acid colitis model via Nrf2/HO-1 pathway in rats.

Methods: In this study, 30 rats were divided into three groups. Acute colitis was induced by rectal administration of 4% solution of acetic acid. MSCs were injected intraperitoneally in the treatment group.

Results: Increased levels of tumor necrosis factor-α (TNF-α), pentraxin-3, and malondialdehyde (MDA) in colitis group were revealed biochemically. Increased level of TNF-α and decreased levels of Nrf2 and interleukin-10 (IL-10) were observed in rectum tissues. Increased fibrous tissue proliferation, vascularization and inflammatory cell infiltration were described in the colitis group. Significant improvement was observed in MSCs treated group histopathologically. Increased immunopositivity of TNF-α, vascular endothelial growth factor (VEGF) and CD68 markers was observed in the colitis group cells, and decreased level of this positivity was observed in MSCs treated group.

Conclusions: Biochemical, histopathological and immunohistochemical results strongly support the ameliorative effect of MSCs against acetic induced colitis model via Nrf2/HO-1 pathway in rats.

目的:探讨间充质干细胞(MSCs)通过Nrf2/HO-1通路对大鼠醋酸性结肠炎模型的改善作用。方法:将30只大鼠分为3组。用4%醋酸溶液直肠灌胃诱导急性结肠炎。治疗组采用腹腔注射MSCs。结果:结肠炎组肿瘤坏死因子-α (TNF-α)、戊曲霉素-3、丙二醛(MDA)水平明显升高。直肠组织中TNF-α水平升高,Nrf2和白细胞介素-10 (IL-10)水平降低。结肠炎组纤维组织增生、血管化和炎症细胞浸润增加。MSCs处理组在组织病理学上有明显改善。结肠炎组细胞中TNF-α、血管内皮生长因子(VEGF)和CD68标志物免疫阳性水平升高,MSCs处理组细胞免疫阳性水平降低。结论:生物化学、组织病理学和免疫组化结果有力支持MSCs通过Nrf2/HO-1途径对大鼠醋酸诱导结肠炎模型的改善作用。
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引用次数: 0
Alternative use of endocavitary probe to guide minimally invasive partial nephrectomy: is it reasonable? 替代使用腔内探针指导微创肾部分切除术:是否合理?
IF 1.1 4区 医学 Q2 Medicine Pub Date : 2022-09-19 eCollection Date: 2022-01-01 DOI: 10.1590/acb370607
Lucas Teixeira Batista, José Guilherme Reis de Oliveira, Vitor Parente Gouvea, Leonardo Azevedo de Souza, Rafael Tourinho-Barbosa

Purpose: To describe the use of endocavitary ultrasound probe as an auxiliary tool when performing partial nephrectomy in cases of endophytic renal tumors, to standardize the method, and to report the preliminary results achieved with this technique.

Methods: Fifteen patients diagnosed with completely endophytic underwent partial nephrectomy with the use of an endocavitary ultrasound probe. This article describes the technique involved in partial nephrectomy and details the preparation of the endocavitary ultrasound probe to ensure its safe use.

Results: All the patients had a RENAL score between 8 and 11. The median time of warm ischemia was 26 and 18 minutes for laparoscopic or robot-assisted surgery, respectively. The median duration of surgery was 150 minutes, and the median console time was 145 minutes for the laparoscopic and robot-assisted surgery groups, respectively. The median estimate of blood loss was 200 mL. Only three patients in the laparoscopic group had focal positive surgical margins. There were no cases of infection at the site of probe entry.

Conclusions: Intraoperative use of an endocavitary ultrasound probe for partial nephrectomy is possible and a safe alternative to the excision of endophytic tumors when neither robotic probes nor laparoscopic probes are available.

目的:介绍在肾内生肿瘤部分切除术中使用腔内超声探头作为辅助工具的情况,规范其方法,并报告该技术的初步结果。方法:15例确诊为完全内生肾病的患者行部分肾切除术,采用腔内超声探头。本文介绍了部分肾切除术所涉及的技术,并详细介绍了腔内超声探头的制备,以确保其安全使用。结果:所有患者的肾功能评分均在8 ~ 11分之间。腹腔镜或机器人辅助手术的中位热缺血时间分别为26分钟和18分钟。腹腔镜组和机器人辅助手术组的中位手术时间分别为150分钟和145分钟。出血量的中位数估计为200毫升。腹腔镜组中只有3例患者有局灶性手术切缘阳性。探针入路部位无感染病例。结论:术中使用腔内超声探头进行部分肾切除术是可行的,在没有机器人探头和腹腔镜探头的情况下,是一种安全的替代内生肿瘤切除术的方法。
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引用次数: 0
The neuroprotective effects of Lutongkeli in traumatic brain injury rats by anti-apoptosis mechanism. 路路通通过抗细胞凋亡机制对脑外伤大鼠的神经保护作用
IF 1.1 4区 医学 Q3 SURGERY Pub Date : 2022-09-19 eCollection Date: 2022-01-01 DOI: 10.1590/acb370603
Qiu-Xia Xiao, Lu-Lu Xue, Zhang-Yu Su, Jin Huang, Ji-Lin Chen, Liu-Lin Xiong, Ting-Hua Wang

Purpose: To explore the neuroprotective effects of Lutongkeli (LTKL) in traumatic brain injury (TBI) and detect the related mechanism.

Methods: TBI model was established with LTKL administration (2 and 4 g/kg/d, p.o.). Motor function of rats was examined by Rotarod test. Nissl staining was used to show neuron morphology. Furthermore, the disease-medicine common targets were obtained with the network pharmacology and analyzed with Kyoto Encyclopedia of Genes and Genomes. Lastly, the predicted targets were validated by real-time polymerase chain reaction.

Results: After LTKL administration, neural behavior was significantly improved, and the number of spared neurons in brain was largely increased. Moreover, 68 bioactive compounds were identified, corresponding to 148 LTKL targets; 2,855 genes were closely associated with TBI, of which 87 overlapped with the LTKL targets and were considered to be therapeutically relevant. Functional enrichment analysis suggested LTKL exerted its pharmacological effects in TBI by modulating multiple pathways including apoptosis, inflammation, etc. Lastly, we found LTKL administration could increase the mRNA level of Bcl-2 and decrease the expression of Bax and caspase-3.

Conclusions: This study reported the neuroprotective effect of LTKL against TBI is accompanied with anti-apoptosis mechanism, which provides a scientific explanation for the clinical application of LTKL in the treatment of TBI.

目的:探讨Lutongkeli(LTKL)对创伤性脑损伤(TBI)的神经保护作用,并检测其相关机制:方法:建立创伤性脑损伤模型,给予LTKL(2和4 g/kg/d,p.o.)。大鼠的运动功能通过旋转测试进行检测。Nissl染色用于显示神经元形态。此外,还利用网络药理学获得了疾病与药物的共同靶点,并利用京都基因和基因组百科全书进行了分析。最后,通过实时聚合酶链反应验证了预测的靶点:结果:服用LTKL后,神经行为明显改善,大脑中受损神经元的数量大幅增加。此外,还发现了68种生物活性化合物,与148个LTKL靶点相对应;2,855个基因与创伤性脑损伤密切相关,其中87个基因与LTKL靶点重叠,被认为具有治疗意义。功能富集分析表明,LTKL通过调节多种通路(包括细胞凋亡、炎症等)在TBI中发挥药理作用。最后,我们发现服用LTKL可提高Bcl-2的mRNA水平,降低Bax和caspase-3的表达:本研究报道了LTKL对创伤性脑损伤的神经保护作用伴随着抗凋亡机制,这为LTKL在创伤性脑损伤治疗中的临床应用提供了科学解释。
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引用次数: 0
Ten years of IRCAD, Barretos, SP, Brazil. 十年的IRCAD,巴雷托斯,SP,巴西。
IF 1.1 4区 医学 Q2 Medicine Pub Date : 2022-09-19 eCollection Date: 2022-01-01 DOI: 10.1590/acb370608
Eduardo Crema, Armando Geraldo Franchini Melani, Luís Gustavo Capochin Romagnolo, Jacques Marescaux

Minimally invasive surgery represented a significant milestone in modern surgery; however, continuous innovation and the emergence of new technologies pose new challenges in terms of surgical learning curves since new interventions are associated with increased surgical complexity and a higher risk of complications. For this reason, surgeons are aware of the beneficial effects of "learning before doing" and the importance of safely implementing new surgical procedures in order to obtain better patient outcomes. Considered the largest Latin American training center in minimally invasive surgery, IRCAD Barretos, São Paulo, Brazil, makes it possible to acquire surgical skills through training in different and the most complex areas of medicine, providing the experience of real and simulated situations, with focus on innovation. The center possesses state-of-the-art infrastructure and technology, with a very high-level teaching staff and an affectionate and hospitable reception. Since its inauguration, in 2011, the center has already qualified numerous professionals and has placed the country in a privileged position in terms of surgical knowledge. The present article describes the activities developed over these ten years of the institute in Brazil as the largest training center for surgeons of the continent in order to address the importance of surgical skills training.

微创手术是现代外科的一个重要里程碑;然而,不断的创新和新技术的出现在手术学习曲线方面提出了新的挑战,因为新的干预措施与增加的手术复杂性和更高的并发症风险相关。出于这个原因,外科医生意识到“先学后做”的有益效果,以及为了获得更好的患者预后,安全实施新的外科手术的重要性。IRCAD Barretos位于巴西圣保罗,被认为是拉丁美洲最大的微创手术培训中心,通过不同和最复杂的医学领域的培训,提供真实和模拟情况的经验,使获得手术技能成为可能,并专注于创新。该中心拥有最先进的基础设施和技术,拥有非常高水平的师资队伍和热情好客的接待。自2011年成立以来,该中心已经培养了许多专业人员,并使该国在外科知识方面处于优势地位。本文描述了这十年来巴西研究所作为非洲大陆最大的外科医生培训中心开展的活动,以解决外科技能培训的重要性。
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引用次数: 0
ERRATA: Kukoamine A activates Akt/GSK-3β signaling pathway to inhibit oxidative stress and relieve myocardial ischemia-reperfusion injury. Kukoamine A激活Akt/GSK-3β信号通路,抑制氧化应激,减轻心肌缺血-再灌注损伤。
IF 1.1 4区 医学 Q2 Medicine Pub Date : 2022-09-09 DOI: 10.1590/acb370407.errata

[This corrects the article doi: 10.1590/acb370407].

[这更正了文章doi: 10.1590/acb370407]。
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引用次数: 0
Microsurgical arterial anastomosis in young and adult rats: an evolutive and comparative study. 幼鼠和成年大鼠动脉吻合的显微外科手术:进化和比较研究。
IF 1.1 4区 医学 Q2 Medicine Pub Date : 2022-09-05 eCollection Date: 2022-01-01 DOI: 10.1590/acb370604
Maria Mercês Santos, Ana Cristina Aoun Tannuri, Adriana Vasconcelos Lacerda, Josiane de Oliveira Gonçalves, Luiz Roberto Schlaich Ricardi, Uenis Tannuri

Purpose: To evaluate the caliber of an arterial micro-anastomosis in the young growing animal using a continuous suture technique. Additionally, late morphological changes and blood flows distal to the anastomosis were evaluated.

Methods: Seventy-four Wistar rats were submitted to laparotomy to access the aorta for blood flow measurement. The aorta was sectioned using microsurgery technique and an end-to-end anastomosis with continuous suture. After a period of six months to one year, the anastomosis was checked.

Results: Regarding the size of the aortas, comparing the pre- and postoperative values, there was an increase of 13.33% in adult animals and 25% in young animals, without any difference in the blood flows.

Conclusions: The arteries of young rats show signs of growth at the site of the anastomosis performed with continuous suture.

目的:评价连续缝合技术在幼龄动物动脉微吻合术中的应用价值。此外,后期形态学变化和血流远端吻合器进行了评估。方法:74只Wistar大鼠开腹进入主动脉进行血流量测量。采用显微外科技术切开主动脉,连续缝合端到端吻合。术后6个月至1年复查吻合情况。结果:主动脉大小与术前、术后比较,成体大鼠增大13.33%,幼体大鼠增大25%,血流量无差异。结论:连续缝合后,幼龄大鼠吻合部位动脉有生长迹象。
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引用次数: 0
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Acta cirurgica brasileira
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