Abstract:
Background:Ischemia preconditioning (IPC) remains the most powerful intervention of protection against myocardial ischemia/reperfusion injury (IRI), but diabetes can weaken or eliminate its cardioprotective effect and detailed mechanisms remain unclear. In this study, we aimed to explore whether changes of autophagy in the diabetic condition are attributable to the decreased cardioprotective effect of IPC. Methods:Sixty diabetic male Sprague-Dawley rats were randomly divided into the control (C), IRI, rapamycin (R), wortmannin (W), rapamycin + IPC (R + IPC), and wortmannin + IPC (W + IPC) groups. The in vivo rat model of myocardial IRI was established by ligaturing and opening the left anterior descending coronary artery via the left thoracotomy. Durations of ischemia and reperfusion are 30 min and 120 min, respectively. Blood samples were taken at 120 min of reperfusion for measuring serum concentrations of troponin I (TnI) and creatine kinase isoenzyme MB (CK-MB) using the enzyme-linked immunosorbent assay. The infarct size was assessed by Evans blue and triphenyltetrazolium chloride staining. The expressions of LC3-II, beclin-1, phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and P-Akt/Akt ratio in the ischemic myocardium were assessed by Western blotting. Results:Compared to the IRI group, infarct size (56.1% ± 6.1% vs. 75.4 ± 7.1%, P < 0.05), serum cTnI (0.61 ± 0.21 vs. 0.95 ± 0.26 ng/ml, P < 0.05), and CK-MB levels (6.70 ± 1.25 vs. 11.51 ± 2.35 ng/ml, P < 0.05) obviously decreased in the W + IPC group. Compared with the C group, myocardial expressions of LC3-II (0.46 ± 0.04 and 0.56 ± 0.04 vs. 0.36 ± 0.04, P < 0.05) and beclin-1 (0.34 ± 0.08 and 0.38 ± 0.07 vs. 0.24 ± 0.03, P < 0.05) evidently increased, and myocardial expressions of mTOR (0.26 ± 0.08 and 0.25 ± 0.07 vs. 0.38 ± 0.06, P < 0.05), PI3K (0.29 ± 0.04 and 0.30 ± 0.03 vs. 0.38 ± 0.02, P < 0.05), and P-Akt/Akt ratio (0.49 ± 0.10 and 0.48 ± 0.06 vs. 0.72 ± 0.07, P < 0.05) markedly decreased in the IRI and R groups, indicating an increased autophagy. Compared with the IRI group, myocardial expression of beclin-1 (0.26 ± 0.03 vs. 0.34 ± 0.08, P < 0.05) significantly decreased, and myocardial expressions of mTOR (0.36 ± 0.04 vs. 0.26 ± 0.08, P < 0.05), PI3K (0.37 ± 0.03 vs. 0.29 ± 0.04, P < 0.05), and P-Akt/Akt ratio (0.68 ± 0.05 vs. 0.49 ± 0.10, P < 0.05) increased obviously in the W + IPC group, indicating a decreased autophagy. Conclusions:Increased autophagy in the diabetic myocardium is attributable to decreased cardioprotection of IPC, and autophagy inhibited by activating the PI3K-Akt-mTOR signaling pathway can result in an improved protection of IPC against diabetic myocardial IRI. :自噬抑制对缺血预处理保护糖尿病大鼠心肌缺血/再灌注损伤的影响摘要背景:缺血预处理(Ischemic preconditioning, IPC)仍然是心肌缺血/再灌注损伤(Ischemia/reperfusion injury,IRI)最强效的保护干预措施,但糖尿病可减弱甚至消除其心肌保护作用,并且具体机制尚不明确。本研究旨在探讨糖尿病条件下自噬改变是否参与了降低的IPC心肌保护作用。 方法:将60只雄性糖尿病Sprague-Dawley大鼠随机分为对照组(C组)、IRI组、雷帕霉素组(R组)、渥曼青霉素组(W组)、雷帕霉素+IPC组(R+IPC组)和渥曼青霉素+IPC组(W+IPC组)。通过左侧开胸结扎和开放左冠状动脉前降支建立大鼠在体心肌IRI模型,心肌缺血和再灌注的时间分别是30分钟和120分钟。再灌注120 min时采集血样,采用酶联免疫吸附法(enzyme-linked immunosorbent essay, ELISA)检测血清心肌肌钙蛋白I(cardiac troponin I,cTnI)和肌酸激酶同工酶MB(creatine kinase isoenzyme MB,CK-MB);采用伊文氏蓝和2,3,5-三苯基氯化四氮唑双染色法测定心肌梗死面积;采用Western-blotting检测LC3-Ⅱ、Beclin-1、mTOR、PI3K心肌表达情况和P-Akt/Akt比率。 结果:与IRI组相比,W+IPC组的心肌梗死面积(56.1%±6.1%比75.4±7.1%,P <0.05),血清cTnI浓度(0.61±0.21比0.95±0.26 ng/ml,P <0.05)、血清CK-MB浓度(6.70±1.25比11.51±2.35 ng/ml,P <0.05)均明显降低;与C组相比,IRI和R组LC3-Ⅱ(0.46±0.04和0.56±0.04比0.36±0.04,P <0.05)和beclin-1(0.34±0.08和0.38±0.07比0.24±0.03,P <0.05)心肌表达明显增强,mTOR(0.26±0.08和0.25 ± 0.07 比 0.38 ± 0.06, P < 0.05)和PI3K(0.29±0.04和0.30±0.03比0.38±0.02,P <0.05)心肌表达以及P-Akt/Akt比率(0.49±0.10和0.48 ± 0.06比0.72 ± 0.07, P < 0.05)明显降低,表明自噬表达增强。与IRI组相比,W+IPC组beclin-1(0.26±0.03比0.34±0.08,P <0.05)心肌表达明显降低,mTOR(0.36±0.04比0.26±0.08,P <0.05)和PI3K(0.37±0.03比0.29±0.04,P <0.05)心肌表达以及P-Akt/Akt比率(0.68±0.05比0.49±0.10,P <0.05)明显增加,表明自噬表达降低。 结论:糖尿病心肌自噬表达增强可减弱IPC的心肌保护作用,激活PI3K-Akt-mTOR信号转导通路抑制自噬可改善IPC对糖尿病心肌IRI的保护作用。.
journal_name
Chin Med J (Engl)journal_title
Chinese medical journalauthors
Liu YY,Sun C,Xue FS,Yang GZ,Li HX,Liu Q,Liao Xdoi
10.4103/0366-6999.235867subject
Has Abstractpub_date
2018-07-20 00:00:00pages
1702-1709issue
14eissn
0366-6999issn
2542-5641pii
ChinMedJ_2018_131_14_1702_235867journal_volume
131pub_type
杂志文章abstract:BACKGROUND:Trichosporon asahii (T. asahii) is one of the most important pathogenic fungus in the genus of trichosporon. Although the species identification of T. asahii was based upon the complicated results of morphologic, biochemical and biologic examination, the morphology characteristic is still the first clue to t...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2009-08-05 00:00:00
abstract::Ninety-five patients with perforation, hemorrhage or stenosis due to duodenal ulcer were treated by extended parietal cell vagotomy. Postoperative follow-up ranged from 3.5 to 10 years (mean 6 years) in 88 patients (92%) with acute perforation (60), hemorrhage (8) and stenosis (20). There was no operative mortality. U...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
abstract:BACKGROUND:The role of plasma high sensitivity C-reactive protein (hs-CRP) in in-stent restenosis (ISR) remains controversial. We investigated plasma hs-CRP level at both admission and follow-up in patients with stable angina (SA) after successful coronary stenting in order to clarify the predictive value of hs-CRP for...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND:Transcatheter bronchial artery embolization (BAE) is widely used for the treatment of hemoptysis and the immediate success rate is high, but there are still some hemorrhage recurrences. One of the common reasons for failure of BAE is collateral branches as blood supply. The inferior phrenic artery (IPA) is o...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2009-03-05 00:00:00
abstract:OBJECTIVE:To describe the methods which were used to develop collagen-based materials for wound dressing. METHODS:Fresh frozen bovine tendon was treated with 0.05 mol/L acetic acid at pH 3.2 for 48-72 hours, homogenized, filtered, mixed with 8% chondroitin sulphate, for creating a deaerated 1.5%-2.5% collagen solution...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2003-03-01 00:00:00
abstract:BACKGROUND:The CHA2DS2-VASc score is used clinically for stroke risk stratification in patients with atrial fibrillation (AF). We sought to investigate whether the CHA2DS2-VASc score predicts stroke and death in Chinese patients with sick sinus syndrome (SSS) after pacemaker implantation and to evaluate whether the pre...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:10.4103/0366-6999.211881
更新日期:2017-08-20 00:00:00
abstract:OBJECTIVE:5-Fluorouracil (5-FU)-based combination therapies are standard treatments for gastrointestinal cancer, where the modulation of autophagy is becoming increasingly important in offering effective treatment for patients in clinical practice. This review focuses on the role of autophagy in 5-FU-induced tumor supp...
journal_title:Chinese medical journal
pub_type: 杂志文章,评审
doi:10.4103/0366-6999.176069
更新日期:2016-02-20 00:00:00
abstract:OBJECTIVE:To investigate whether PreS1 antigen and/or anti-PreS1 antibody in serum might have some significance different from routine hepatitis B virus (HBV) markers in hepatitis B virus infection. METHODS:Forty-six acute hepatitis B patients and 377 chronic persistent hepatitis patients were examined to assess the c...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:1999-04-01 00:00:00
abstract:BACKGROUND:Coexistent carotid and coronary artery diseases are common and patients with them remain at a high risk for perioperative stroke or myocardial infarction after coronary bypass surgery. The aim of this study was to investigate the effect of combined carotid endarterectomy (CEA) and off-pump coronary artery by...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2009-12-20 00:00:00
abstract:Background:Signal transducer and activator of transcription 3 (STAT3) was strongly expressed and activated in psoriatic keratinocytes (KCs) and correlated with the severity of psoriasis. The study aimed to investigate the effects of STAT3 small interfering RNA (siRNA) combined with ultrasonic irradiation and SonoVue mi...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:10.4103/0366-6999.239297
更新日期:2018-09-05 00:00:00
abstract:BACKGROUND:A number of methods have been used in the treatment of symptomatic and aggressive vertebral hemangioma, but none of them is optimal. Vertebral hemangioma treated with cement vertebroplasty or ethanol injection alone showed relatively good results despite their limitations. METHODS:Between February 2002 and ...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2007-07-05 00:00:00
abstract:BACKGROUND:This prospective, randomized, controlled study was designed to investigate the effects of a diabetes specific formula (Diason low energy: 313.8 kJ/100 ml), compared with a standard formula, on insulin sensitivity, serum C peptide, serum lipids and free fatty acid (FFA) in type 2 diabetics. METHODS:In total ...
journal_title:Chinese medical journal
pub_type: 杂志文章,随机对照试验
doi:
更新日期:2008-04-20 00:00:00
abstract:BACKGROUND:Associations between glutamine (Gln) enriched nutrition support and surgical patients with gastrointestinal (GI) tumor remain controversy. The purpose of this meta-analysis was to assess the effect of Gln enriched nutrition support on surgical patients with GI tumor in term of relevant biochemical indices, i...
journal_title:Chinese medical journal
pub_type: 杂志文章,meta分析
doi:10.4103/0366-6999.149219
更新日期:2015-01-20 00:00:00
abstract:BACKGROUND:Expression of murine calcium-activated chloride channel family member 3 (mCLCA3) has been reported to be increased in the airway epithelium of asthmatic mice challenged with ovalbumin (OVA). However, its role in asthmatic airway inflammation under no OVA exposure has not yet been clarified. METHODS:mCLCA3 p...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2013-01-01 00:00:00
abstract::The radiographic measurement of the prevertebral soft tissue of cervical vertebrae was performed in 87 normal adults. According to the results of the measurement, 10 mm and 20 mm were used as the upper limit normal values of the retropharyngeal and retrotracheal space respectively. We conclude that although the widene...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract:BACKGROUND:In the past 5 years, new treatment materials and techniques offering a different concept in endovascular treatment have been described for cerebral arteriovenous malformations (CAVMs). The aim of this study was to assess the endovascular treatment of CAVMs by using a liquid embolic material, Onyx (Micro Ther...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2005-12-20 00:00:00
abstract:BACKGROUND:Borderline gastrointestinal stromal tumors (GISTs) are intermediate tumors between benign and malignant variants; however, the clinical and pathological features of borderline GISTs remain poorly defined. This study aimed to characterize GISTs and to identify a set of borderline criteria for practical use. ...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND:To study the characters of high-frequency oscillations (HFOs) in the seizure onset zones (SOZ) and the nonseizure onset zones (NSOZ) in the electrocorticography (ECoG) of patients with neocortical epilepsy. METHODS:Only patients with neocortical epilepsy who were seizure-free after surgery as determined wit...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:10.4103/0366-6999.159342
更新日期:2015-07-05 00:00:00
abstract::It is difficult to make a precise diagnosis of intestinal tuberculosis and to differentiate it from Crohn's disease. For evaluating Polymerase Chain Reaction (PCR) assay in these two aspects, 36 specimens of intestinal tuberculosis from surgical resections and endoscopic biopsies and 26 Crohn's disease samples were su...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract:BACKGROUND:Myocardial protection during off-pump coronary artery bypass grafting (OPCABG) is a multifactorial problem in which maintaining stable systemic hemodynamics is very important. In this study passive graft perfusion (PGP) was applied to investigate the effect during and after OPCABG as evaluated by cardiac tro...
journal_title:Chinese medical journal
pub_type: 杂志文章,随机对照试验
doi:
更新日期:2007-02-05 00:00:00
abstract:BACKGROUND:The mechanisms underlying postoperative pain remain unclear. Neurotransmitters of excitatory and inhibitory amino acids play an important role in the transmission and modulation of pain in the spinal dorsal horn. This study aimed to investigate the changes of release of excitatory and inhibitory amino acids ...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2007-11-20 00:00:00
abstract:BACKGROUND:The effects of oral contrast agents (OCAs) on dosimetry have not been studied in detail. Therefore, this study aimed to examine the influence of OCAs on dose calculation in volumetric-modulated arc therapy plans for rectal cancer. METHODS:From 2008 to 2016, computed tomography (CT) images were obtained from...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:10.1097/CM9.0000000000001025
更新日期:2020-09-05 00:00:00
abstract:OBJECTIVE:To study the analgesic mechanism of gabapentin, an anticonvulsant, during antinociceptive clinical treatment. METHODS:Whole-cell voltage-clamp recordings were taken from adult rat spinal cord slices to investigate the effect of gabapentin on primary afferent A delta-fiber evoked excitatory postsynaptic curre...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2003-06-01 00:00:00
abstract:BACKGROUND:Trocar-site hernia (TSH) is a serious complication after laparoscopic procedures. Although it is a rare entity, it can have life-threatening consequences. This study aimed to retrospectively analyze the potential associated factors for TSH following gynecologic laparoscopy and summarize prevention strategies...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:10.1097/CM9.0000000000000510
更新日期:2019-11-20 00:00:00
abstract:OBJECTIVE:To analysis the pathological demography in Chinese patients undergoing renal biopsy from our nephrology center. METHODS:Between January 1979 and October 2000 in Jinling Hospital, Nanjing, China, 10,002 attempts of percutaneous renal were performed in patients with renal disease from 33 provinces of China. Th...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2003-09-01 00:00:00
abstract:BACKGROUND:Pulmonary endarterectomy is safe and effective surgical treatment for chronic thromboembolic pulmonary hypertension. This study aimed to evaluate the efficacy of pulmonary endarterectomy in treatment of thromboembolic pulmonary hypertension. METHODS:A retrospective study of 15 patients who underwent pulmona...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2010-04-20 00:00:00
abstract:OBJECTIVE:To observe the immediate angiographic and intravascular ultrasound (IVUS) results and their effects on one month clinical outcomes in forty-one patients who submitted to coronary stent deployment with IVUS guidance. METHODS:All patients were allocated to coronary stent implantation with high inflation pressu...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract:BACKGROUND:The present study was undertaken to replicate the associations of representative polymorphisms in three genes (complement factor H (CFH), complement factor B (BF) and HtrA serine peptidase 1 (HTRA1)) with exudative age-related macular degeneration (AMD) in a Han Chinese population, and to test if the modifia...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2008-12-20 00:00:00
abstract:OBJECTIVE:To rapidly and economically obtain knowledge about adult stage Schistosoma japonicum (Chinese strain) expressed genes using expressed sequence tag (EST). METHODS:A directional cDNA library constructed from Schistosoma japonicum (Chinese strain) adult stage RNA was used to generate expressed sequence tags (ES...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00
abstract:OBJECTIVE:To investigate the effects of propofol, midazolam and thiopental sodium on outcomes and amino acid accumulation in focal cerebral ischemia-reperfusion in rats. METHODS:Male Sprague Dawley (SD) rats were scheduled to undergo 3-hour middle cerebral artery occlusion by intraluminal suture and 24-hour reperfusio...
journal_title:Chinese medical journal
pub_type: 杂志文章
doi:
更新日期:2003-02-01 00:00:00