西格列汀对糖尿病小鼠心肌重构和自噬的影响及其机制

目的: 探讨西格列汀对糖尿病小鼠心肌重构和自噬的影响和可能的机制。方法: 10周龄的C57小鼠腹腔注射STZ 50 mg/(kg·d),连续注射5 d,7 d测血糖浓度＞16.7 mmol/L视为糖尿病小鼠造模成功,造模成功4周后给与药物干预。本实验分四组,对照组(control, 腹腔注射等体积的缓冲液, n=10)、模型组(Streptozocin, STZ腹腔注射诱导糖尿病模型,n=8)、处理组(在模型组基础上给与西格列汀灌胃10 mg/(kg·d),n=8)、抑制剂组(在处理组的基础上给与腹腔注射Compound C (AMPK通路抑制剂,10 mg/(kg·d),n=8),对照组腹腔注射等体积缓冲液,6周后称体重,处死,取小鼠心脏并分离心室称重,计算心室/体重比,HE染色观察心肌细胞形态,Masson染色观察纤维化程度,Western blot 检测心肌脑钠肽(BNP)、转化生长因子β(TGF-β)、缝隙连接蛋白43(Cx43)、AMP依赖的蛋白激酶(AMPK)、LC3B蛋白表达。结果: 给药6周后,与对照组相比,模型组小鼠体重没有明显改变,心室/体重比明显增加(P＜0.05),苏木素-伊红(HE)染色显示细胞增大,Masson染色显示心肌间隙纤维化增多,BNP、TGF-β蛋白明显升高,Cx43、LC3B、AMPK蛋白下降(P＜0.05)。与模型组相比,西格列汀组BNP、TGF-β蛋白明显下降,Cx43、LC3B、AMPK蛋白增多(P＜0.05)。然而Compound C会抑制Cx43、LC3B、AMPK蛋白表达的上调(P＜ 0.05)。结论: 西格列汀可以改善糖尿病小鼠心肌肥厚和纤维化,并且可以通过AMPK相关通路调节Cx43和自噬。     

钙敏感受体通过JNK途径参与内毒素心肌损伤*

目的: 观察内毒素所致的心肌损伤中,钙敏感受体(CaSR)对c-Jun氨基末端激酶 (JNK)途径的影响。方法: 腹腔注射内毒素(5 mg/kg)制作新生大鼠内毒素心肌损伤模型,Wistar新生大鼠随机分为6组:对照组、内毒素组、CaSR激动剂组、CaSR抑制剂组、JNK抑制剂组、CaSR抑制剂+JNK抑制剂组。HE染色观察心肌形态, 测定血清乳酸脱氢酶(LDH)含量,PCR检测IL-6的mRNA表达,Western blot检测CaSR及JNK的蛋白表达。结果: 与对照组相比,内毒素组心肌损伤加重,LDH含量、IL-6的mRNA表达、CaSR和JNK的蛋白表达均明显增加(P＜0.05)。与内毒素组比较,CaSR激动剂组心肌损伤加重,LDH含量、IL-6的mRNA表达、CaSR和JNK的蛋白表达增加(P＜0.05); CaSR抑制剂组心肌损伤减轻,LDH含量、CaSR和JNK的蛋白表达减少(P＜0.05);JNK抑制剂组心肌损伤进一步减轻,LDH含量、IL-6的mRNA表达、CaSR和JNK的蛋白表达均减少(P＜0.05);CaSR抑制剂+JNK抑制剂组心肌损伤明显减轻,LDH含量、IL-6的mRNA表达、CaSR和JNK的蛋白表达进一步减少(P＜0.05)。结论: CaSR可能通过JNK途径参与内毒素所致的心肌损伤。     

复方丹参滴丸联合沙库巴曲缬沙坦对老年心肌梗死患者PCI术后炎性反应、心室重塑和心肌灌注的影响

摘要 目的：探讨复方丹参滴丸联合沙库巴曲缬沙坦对老年心肌梗死患者经皮冠状动脉介入术（percutaneous coronary intervention,PCI）术后炎性反应、心室重塑和心肌灌注的影响。方法：采用随机数字表法将本院2017年3月至2020年2月间收治的行PCI治疗的68例老年心肌梗死为研究对象,分为对照组（34例）和观察组（34例）。两组均行常规药物治疗,在此基础上予以对照组沙库巴曲缬沙坦治疗,予以观察组复方丹参滴丸联合沙库巴曲缬沙坦治疗。比较两组治疗前后血浆中超敏C反应蛋白（high-sensitivity creactive protein,hs-CRP)、肿瘤坏死因子-α（Tumor necrosis factor-α,TNF-α）、白细胞介素-8（interleukin-8,IL-8）、N末端脑钠肽前体（N-terminal-pro-brain-natriuretic-peptide,NT-proBNP）、左室舒张末期前后径（left ventricular end-diastolic diamete,LVEDD）、左室射血分数（left ventricular ejection fraction,LVEF）、左室质量指数（left ventricular mass index,LVMI）以及治疗后TIMI血流分级。结果：两组血浆hs-CRP、TNF-α、IL-8和NT-proBNP水平以及LVEDD和LVMI水平较治疗前明显降低,LVEF水平明显增加（P<0.05）。观察组治疗后血浆hs-CRP、TNF-α、IL-8和NT-proBNP水平以及LVEDD和LVMI水平明显低于对照组,LVEF水平明显高于对照组（P<0.05）。两组术后20 minTIMI血流分级均明显好转,观察组术后20 min时TIMI血流分级明显优于对照组（P<0.05）。两组不良反应总发生率比较无明显差异（P>0.05）。结论：复方丹参滴丸联合沙库巴曲缬沙坦能够明显降低老年心肌梗死患者PCI术后炎性反应,抑制心室重塑,改善心肌灌注,安全性较高。     

急性心肌梗死患者PCI术后心室重构患者血清Hcy、CysC、MMP-1、NGAL的表达及临床意义

摘要 目的：观察急性心肌梗死（AMI）患者经皮冠脉介入术（PCI）术后心室重构患者血清同型半胱氨酸（Hcy）、胱抑素C（CysC）、基质金属蛋白酶-1（MMP-1）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）的表达及临床意义。方法：选取2018年3月~2020年9月期间我院收治的AMI患者70例。根据PCI术后是否发生心室重构将其分为无心室重构组（n=49）和心室重构组（n=21）。检测患者血清MMP-1、Hcy、NGAL、CysC水平及心功能指标[左室后壁厚度( LVPWT)、左室舒张末期内径( LVEDD)、左室射血分数( LVEF)、室间隔厚度( IVST)]。分析血清MMP-1、Hcy、NGAL、CysC水平与心功能指标的相关性。分析AMI患者PCI术后心室重构的影响因素。结果：心室重构组血清MMP-1、Hcy、NGAL、CysC水平均高于无心室重构组（P<0.05）;LVEDD、IVST、 LVPWT均大于无心室重构组,LVEF低于无心室重构组（P<0.05）。Pearson相关性分析结果显示：血清MMP-1、Hcy、NGAL、CysC水平和LVEDD、IVST、 LVPWT均呈正相关,而与LVEF呈负相关（P<0.05）。单因素分析结果显示：两组患者梗死部位、心律失常情况、单核细胞（MO）、肌酸激酶同功酶（CK-MB）、发病到开通梗死相关动脉时间组间对比差异均有统计学意义（P<0.05）。多因素Logistic回归分析结果显示：梗死部位为前壁、发生心律失常以及高水平的MO、CK-MB、MMP-1、Hcy、CysC均是AMI患者PCI术后发生心室重构的危险因素（P<0.05）。结论：血清MMP-1、Hcy、NGAL、CysC表达均与AMI患者PCI术后的心室重构密切相关,检测以上指标水平可对AMI患者PCI术后心室重构的预测和防治提供一定参考。     

Mild hypothermia in rat with acute myocardial ischaemia-reperfusion injury complicating severe sepsis

Myocardial ischemia-reperfusion injury (MIRI) with concurrent severe sepsis has led to substantial mortality. Mild hypothermia (MHT) has been proved to have a therapeutic effect in either MIRI or severe sepsis, which suggests it might be beneficial for MIRI complicating severe sepsis. In this study, Sprague-Dawley rats with MIRI complicating severe sepsis were allotted in either MHT (33 ± 0.5°C) group or normothermia (NT, 37 ± 0.5°C) group; as control, rats receiving sham surgery and normal saline were kept at NT. After 2h of temperature maintenance, blood and heart tissue were acquired for detections. Lactate dehydrogenase (LDH) and MB isoenzyme of creatine kinase (CK-MB) in blood, triphenyl tetrazolium chloride and Evans blue staining, hematoxylin and eosin staining for myocardium were employed to detect myocardial damage. Tumor necrosis factor (TNF)-α and caspase-3 was performed by immunohistochemistry to exam myocardial inflammation and apoptosis. Detection of NADPH oxidase (NOX) 2 was for myocardial oxidative stress. In MHT group, systolic blood pressure was improved significantly compared with NT group. Myocardial infarct size, morphological change, LDH and CK-MB levels were attenuated compared to NT group. Moreover, less expressions of TNF-α, caspase-3 and NOX2 in MHT group were presented compared with NT group. MHT showed cardioprotection by improving cardiac dysfunction, reducing myocardial infarct size and attenuating myocardial injury, inflammation, apoptosis and oxidative stress.     

Sonothrombolysis in the ambulance for ST-elevation myocardial infarction: rationale and protocol

BackgroundTreatment of ST-elevation myocardial infarction (STEMI) has improved over the years. Current challenges in the management of STEMI are achievement of early reperfusion and the prevention of microvascular injury. Sonothrombolysis has emerged as a potential treatment for acute myocardial infarction, both for epicardial recanalisation as well as improving microvascular perfusion. This study aims to determine safety and feasibility of sonothrombolysis application in STEMI patients in the ambulance.MethodsTen patients with STEMI will be included and treated with sonothrombolysis in the ambulance during transfer to the PCI centre. Safety will be assessed by the occurrence of ventricular arrhythmias and shock during sonothrombolysis intervention. Feasibility will be assessed by the extent of protocol completion and myocardial visibility. Efficacy will be determined by angiographic patency rate, ST-elevation resolution, infarct size and left ventricular volumes, and function measured with cardiovascular magnetic resonance imaging, and contrast and strain echocardiography. A comparison will be made with matched controls using an existing STEMI database.DiscussionSonothrombolysis is a novel technique for the treatment of cardiovascular thromboembolic disease. The first clinical trials on its use for STEMI have demonstrated promising results. This study will be the first to examine the feasibility of in-ambulance sonothrombolysis for STEMI.Trial registrationEU Clinical Trials Register (identifier: 2019-001883-31), registered 2020-02-25.     

LncRNA TUG1 acts as a competing endogenous RNA to mediate CTGF expression by sponging miR-133b in myocardial fibrosis after myocardial infarction

Myocardial fibrosis (MF) is one of the basic causes of many cardiovascular diseases. Noncoding RNAs (ncRNAs), including microRNA (miRNA) and long noncoding RNA (lncRNA), have been reported to play an indispensable role in MF. The current work is focused on investigating the biological role of lncRNA taurine upregulation gene 1 (TUG1) in activating cardiac myofibroblasts as well as the underlying mechanism. The outcome revealed that after myocardial infarction TUG1 expression increased and miR-133b expression decreased in the rat model of MF. The expression level of TUG1 increased following AngII treatment in cardiac myofibroblast. TUG1 knockdown inhibited the Ang-II induced cardiac myofibroblast activation and TUG1 overexpression increased proliferation and collagen generation of cardiac myofibroblasts. Bioinformatic prediction programs predicted that TUG1 had MRE directly combined with miR-133b seed sequence, luciferase activity, and RIP experiments indicated that TUG1, acted as a sponger and interacted with miR-133b in cardiac myofibroblasts. Furthermore, a target of miR-133b was CTGF and CTGF knockdown counteracted the promotion of MF by miR-133b knockdown. Collectively, our study suggested that TUG1 mediates CTGF expression by sponging miR-133b in the activation of cardiac myofibroblasts. The current work reveals a unique role of the TUG1/miR-133b/CTGF axis in MF, thus suggesting its immense therapeutic potential in the treatment of cardiac diseases.     

Reviewing the role of cardiac exosomes in myocardial repair at a glance

Exosome-based therapy is an emerging novel approach for myocardial infarction (MI) treatment. Exosomes are identified as extracellular vesicles that are produced within multivesicular bodies in the cells' cytosols and then are secreted from the cells. Exosomes are 30–100 nm in diameter that are released from viable cells and are different from other secreted vesicles such as apoptotic bodies and microvesicles in their origin and contents such as RNAs, proteins, and nucleic acid. The recent advances in exosome research have demonstrated the role of these bionanovesicles in the physiological, pathological, and molecular aspects of the heart. The results of in vitro and preclinical models have shown that exosomes from different cardiac cells can improve cardiac function following MI. For example, mesenchymal stem cells (MSCs) and cardiac progenitor cells (CPCs) containing exosomes can affect the proliferation, survival, and differentiation of cardiac fibroblasts and cardiomyocytes. Moreover, MSCs- and CPCs-derived exosomes can enhance the migration of endothelial cells. Exosome-based therapy approaches augment the cardiac function by multiple means, such as reducing fibrosis, stimulation of vascular angiogenesis, and proliferation of cardiomyocytes that result in replacing damaged heart tissue with newly generated functional myocytes. This review article aims to briefly discuss the recent advancements in the role of secreted exosomes in myocardial repair by focusing on cardiac cells-derived exosomes.     

Laser-heated needle for biopsy tract ablation: In vivo study of rabbit liver biopsy

PurposeTo investigate the efficacy of a newly-developed laser-heated core biopsy needle in the thermal ablation of biopsy tract to reduce hemorrhage after biopsy using in vivo rabbit’s liver model.Materials and methodsFive male New Zealand White rabbits weighed between 1.5 and 4.0 kg were anesthetized and their livers were exposed. 18 liver biopsies were performed under control group (without tract ablation, n = 9) and study group (with tract ablation, n = 9) settings. The needle insertion depth (~3 cm) and rate of retraction (~3 mm/s) were fixed in all the experiments. For tract ablation, three different needle temperatures (100, 120 and 150 °C) were compared. The blood loss at each biopsy site was measured by weighing the gauze pads before and after blood absorption. The rabbits were euthanized immediately and the liver specimens were stained with hematoxylin-eosin (H&E) for further histopathological examination (HPE).ResultsThe average blood loss in the study group was reduced significantly (p < 0.05) compared to the control group. The highest percentage of bleeding reduction was observed at the needle temperature of 150 °C (93.8%), followed by 120 °C (85.8%) and 100 °C (84.2%). The HPE results show that the laser-heated core biopsy needle was able to cause lateral coagulative necrosis up to 14 mm diameter along the ablation tract.ConclusionThe laser-heated core biopsy needle reduced hemorrhage up to 93.8% and induced homogenous coagulative necrosis along the ablation tract in the rabbits’ livers. This could potentially reduce the risk of tumor seeding in clinical settings.     

Effects of eyestalk ablation and limb amputation on the moult cycle of the shrimp Penaeus chinensis

The shrimp Penaeus chinensis at moult stage D_o were subjected to one of the three following treatments: bilateral eyestalk ablation, amputation of the fifth pair of pereiopods, and both of the above treatments. Two consecutive ecdyses after treatments were followed. Intact animals served as control. Precocious moulting was exhibited in all treated groups. Eyestalk ablation shortened the time to the first ecdysis more than does limb amputation. Additive effect was found in shrimps receiving both treatments. The duration between the first and second ecdyses in treated shrimps was shorter than that of intact animals, but the durations in the three treated groups were not significantly different from one another. Regenerates of limbs appeared after the second ecdysis following limb amputation. Further, change of body colour from black and green to red and white was observed in shrimps with eyestalk ablation.