简介:AbstractBackground:Cardiac remodeling after acute myocardial infarction (AMI) is an important process. The present study aimed to assess the protective effects of astaxanthin (ASX) on cardiac remodeling after AMI.Methods:The study was conducted between April and September 2018. To create a rat AMI model, rats were anesthetized, and the left anterior descending coronary artery was ligated. The rats in the ASX group received 10 mg·kg-1·day-1 ASX by gavage for 28 days. On the 1st day after AMI, but before ASX administration, six rats from each group were sacrificed to evaluate changes in the heart function and peripheral blood (PB) levels of inflammatory factors. On the 7th day after AMI, eight rats from each group were sacrificed to evaluate the PB levels of inflammatory factors and the M2 macrophage count using both immunofluorescence (IF) and flow cytometry (FC). The remaining rats were observed for 28 days. Cardiac function was examined using echocardiography. The inflammatory factors, namely, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10, were assessed using enzyme-linked immunosorbent assay. The heart weight/body weight (BW), and lung weight (LW)/BW ratios were calculated, and myocardial fibrosis in the form of collagen volume fraction was measured using Masson trichrome staining. Hematoxylin and eosin (H&E) staining was used to determine the myocardial infarct size (MIS), and TdT-mediated dUTP nick-end labeling staining was used to analyze the myocardial apoptosis index. The levels of apoptosis-related protein, type I/III collagen, transforming growth factor β1 (TGF-β1), metalloproteinase 9 (MMP9), and caspase 3 were assessed by Western blotting. Unpaired t-test, one-way analysis of variance, and non-parametric Mann-Whitney test were used to analyze the data.Results:On day 1, cardiac function was worse in the ASX group than in the sham group (left ventricular end-systolic diameter [LVIDs]: 0.72 ± 0.08 vs. 0.22 ± 0.06 cm, t= -11.38; left ventricular end-diastolic diameter [LVIDd]: 0.89 ± 0.09 vs. 0.48 ± 0.05 cm, t= -9.42; end-systolic volume [ESV]: 0.80 [0.62, 0.94] vs. 0.04 [0.03, 0.05] mL, Z = -2.89; end-diastolic volume [EDV]: 1.39 [1.03, 1.49] vs. 0.28 [0.22, 0.32] mL, Z = -2.88; ejection fraction [EF]: 0.40 ± 0.04 vs. 0.86 ± 0.05, t= 10.00; left ventricular fractional shortening [FS] rate: 0.19 [0.18, 0.20] %FS vs. 0.51 [0.44, 0.58] %FS, Z = -2.88, all P < 0.01; n = 6). The levels of inflammatory factors significantly increased (TNF-α: 197.60 [133.89, 237.94] vs. 50.48 [47.21 57.10] pg/mL, Z= -2.88; IL-1β: 175.23 [160.74, 215.09] vs. 17.78 [16.83, 19.56] pg/mL, Z = -2.88; IL-10: 67.64 [58.90, 71.46] vs. 12.33 [11.64, 13.98] pg/mL, Z = -2.88, all P < 0.01; n = 6). On day 7, the levels of TNF-α and IL-1β were markedly lower in the ASX group than in the AMI group (TNF-α: 71.70 [68.60, 76.00] vs. 118.07 [106.92, 169.08] pg/mL, F = 42.64; IL-1β: 59.90 [50.83, 73.78] vs. 151.60 [108.4, 198.36] pg/mL, F = 44.35, all P < 0.01, n = 8). Conversely, IL-10 levels significantly increased (141.84 [118.98, 158.36] vs. 52.96 [42.68, 74.52] pg/mL, F= 126.67, P < 0.01, n = 8). The M2 macrophage count significantly increased (2891.42 ± 211.29 vs. 1583.38 ± 162.22, F= 274.35, P < 0.01 by immunofluorescence test; 0.96 ± 0.18 vs. 0.36 ± 0.05, F= 46.24, P < 0.05 by flowcytometry test). On day 28, cardiac function was better in the ASX group than in the AMI group (LVIDs: 0.50 [0.41, 0.56] vs. 0.64 [0.56, 0.74] cm, Z = -3.60; LVIDd: 0.70 [0.60, 0.76] vs. 0.80 [0.74 0.88] cm, Z = -2.96; ESV: 0.24 [0.18, 0.45] vs. 0.58 [0.44, 0.89] mL, Z = -3.62; EDV: 0.76 [0.44, 1.04] vs. 1.25 [0.82, 1.46] mL, Z = -2.54; EF: 0.60 ± 0.08 vs. 0.50 ± 0.12, F= 160.48; % FS: 0.29 [0.24, 0.31] vs. 0.20 [0.17, 0.21], Z = -4.43, all P < 0.01; n = 16). The MIS and LW/BW ratio were markedly lower in the ASX group than in the AMI group (myocardial infarct size: 32.50 ± 1.37 vs. 50.90 ± 1.73, t = 23.63, P < 0.01, n = 8; LW/BW: 1.81 ± 0.15 vs. 2.17 ± 0.37, t= 3.66, P = 0.01, n = 16). The CVF was significantly lower in the ASX group than in the AMI group: 12.88 ± 2.53 vs. 28.92 ± 3.31, t = 10.89, P < 0.01, n = 8. The expression of caspase 3, TGF-β1, MMP9, and type I/III collagen was lower in the ASX group than in the AMI group (caspase 3: 0.38 ± 0.06 vs. 0.66 ± 0.04, t= 8.28; TGF-β1: 0.37 ± 0.04 vs. 0.62 ± 0.07, t = 6.39; MMP9: 0.20 ± 0.06 vs. 0.40 ± 0.06, t = 4.62; type I collagen: 0.42 ± 0.09 vs. 0.74 ± 0.07, t = 5.73; type III collagen: 0.13 ± 0.02 vs. 0.74 ± 0.07, t = 4.32, all P < 0.01; n = 4).Conclusions:ASX treatment after AMI may promote M2 macrophages and effectively attenuate cardiac remodeling by inhibiting inflammation and reducing myocardial fibrosis.
简介:摘要目的探讨在癌症晚期失禁性皮炎患者护理过程中,3M液体敷料的应用效果,旨在提升患者临床护理有效率.方法选取2014年4月至2015年5月我院收治的癌症晚期失禁性皮炎患者78例,对照组患者主要进行常规临床护理,观察组患者主要在对照组护理基础上应用3M液体敷料进行护理,研究分析两组患者皮肤护理有效情况.结果在患者皮炎愈合情况上,观察组明显优于对照组,在患者临床护理有效情况上,观察组也明显优于对照组.结论3M液体敷料在癌症晚期患者失禁性皮炎中的临床作用较大.关键词3M液体敷料;癌症晚期患者;失禁性皮炎;护理效果;对比AbstractObjectivetostudythepatientswithterminalcancerincontinentdermatitisnursingprocess,theapplicationeffectof3mliquiddressing,designedtoimprovetheclinicalnursingefficiency.MethodstochoosebetweenApril2014andMay2014,ourhospital78casesofpatientswithterminalcancerincontinentdermatitis,thecontrolgrouppatientsinroutineclinicalcare,onthebasisoftheobservationgroupofpatientsinthecontrolgroupcare3mliquiddressingwasusedtocare,twogroupsofpatientswithskincareresearchanalysiseffectively.Resultsonthehealingofpatientswithdermatitis,theobservationgroupwasbetterthancontrolgroup,effectiveconditioninclinicalnursing,observationgroupisobviouslybetterthanthecontrolgroup.Conclusion3mliquiddressinginterminalcancerpatientKseywiwthortdhseclinicalroleofincontinentdermatitis.3mliquiddressing;Terminalcancerpatients;Incontinentdermatitis;Nursingeffect;contrast中图分类号R473.7文献标识码B文章编号1008-6315(2015)12-1030-01
简介:摘要目的探究单体型B与线粒体m.1555A>G突变致聋的相关性。方法采集单体型为B且携带m.1555A>G家系(TP023)成员外周血,建立永生化淋巴细胞系作为实验组(D组);选取单体型非B但携带m.1555A>G的永生化淋巴细胞(S组)和单体型为B但不携带m.1555A>G的永生化淋巴细胞(C组)为对照组;分别对三组细胞的线粒体膜电位(mitochondrial membrane potential,MMP)、线粒体蛋白表达、细胞活性氧(reactive oxygen species,ROS)、三磷酸腺苷(adenosine triphosphate,ATP)水平进行检测,评估线粒体功能。结果相比于C组,D组细胞的MMP下降29.5%(P<0.001),ROS水平上升30.8%(P<0.001),ATP产量下降39.0%(P<0.001),S组细胞MMP下降21.3%(P=0.002),ROS水平上升8.7%(P=0.202),ATP产量下降11.2%(P=0.661);两组细胞的ND4、CytB等蛋白表达均有不同程度的下降。结论线粒体单体型B可能是导致m.1555A>G突变携带者的耳聋外显率增高的原因。
简介:摘要6-甲基腺嘌呤(N6-methyladenosine,m6A)是真核生物mRNA中最丰富的内部化学修饰,参与了许多转录后的调控过程,包括维持mRNA的稳定性、促进其剪接和翻译。在哺乳动物中,m6A的动态变化调节动物的生长、发育和代谢。相反,营养和饮食也可以通过调节m6A甲基化模式来调节基因表达。本文主要专注于m6A修饰与营养生理和代谢之间的相互作用研究。
简介:摘要目的探讨脱氧胆酸(DCA)对人外周血来源巨噬细胞(PBDM)极化的影响。方法分离培养人外周血巨噬细胞(PBDM)。采用细胞计数试剂(CCK-8)法检测25、50、100、150、200 μmol/L DCA对PBDM细胞活性的影响。将PBDM细胞分为对照组和3个实验组,实验组分别加入50、100、150 μmol/L的DCA。反转录-聚合酶链反应(RT-PCR)法检测各组促炎细胞因子白细胞介素(IL)-6、IL-1β、肿瘤坏死因子-α(TNF-α)及抑炎细胞因子IL-10、CD206的mRNA水平,流式细胞术检测M1型巨噬细胞表面标志物CD86的表达。多组计数资料比较采用方差分析,两两比较采用t检验。结果实验组IL-6在100、150 μmol/L DCA处理后显著高于对照组(2.67±0.32、4.56±0.21比1.00±0.03,F=243.291,P<0.01),TNF-α在100、150 μmol/L DCA处理后显著高于对照组(1.86±0.23、2.70±0.12比1.05±0.23,F=193.384,P<0.01),IL-1β在50、100、150 μmol/L DCA处理后显著高于对照组(12.02±0.13、13.85±1.01、15.30±1.03比1.03±0.11,F=1 192.321,P<0.01)。实验组IL-10在100、150 μmol/L DCA处理后显著低于对照组(0.76±0.13、0.64±0.26比1.03±0.13,F=287.184,P<0.01),实验组CD206在150 μmol/L DCA处理后显著低于对照组(0.61±0.11比1.02±0.04,F=107.312,P<0.05);PBDM中CD86表达比例在50、100、150 μmol/L DCA处理后显著高于对照组(16.50±0.25、20.31±1.04、22.25±0.89比3.37±0.15,F=312.545,P<0.01)。结论DCA可诱导人PBDM向M1型极化。
简介:摘要N6-甲基腺嘌呤(N6-methyladenosine,m6A)甲基化作为真核生物中最常见的RNA修饰,通过甲基化转移酶、去甲基化酶、甲基化识别蛋白三种调控因子参与多种细胞进程和疾病进展。近年来的研究表明m6A甲基化修饰参与了精子发生的整个过程,其失调造成的生精障碍可能导致男性不育。本文就m6A调控因子在睾丸中的时空表达、m6A甲基化在精子发生中的作用机制以及m6A甲基化调控异常与男性不育等方面的研究进展作一综述,旨在为男性不育的基础研究和临床治疗提供参考。
简介:摘要目的探讨临床罕见的Möbius综合征(MBS)的临床特征及可能的致病基因。方法横断面研究。对2018年7月至2021年12月就诊于首都医科大学附属北京同仁医院北京同仁眼科中心的18例散发MBS患者进行一般信息问卷调查、详细眼科检查和全身体格检查,其中17例患者行颅神经及眼眶MRI。采集所有患者及核心家系成员的外周静脉血,提取基因组DNA,应用全外显子组测序及生物信息学分析方法鉴定可能导致MBS的致病基因变异。结果在18例患者中,男性8例,女性10例;年龄为(4.5±4.0)岁(8个月至17岁)。18例患者均存在先天性单侧或双侧眼球外转受限及面瘫,符合MBS的最低诊断标准。其中,以双侧眼球外转受限(16例)及双侧面瘫(15例)更为多见。18例患者中,第一眼位正位9例,内斜视8例,下斜视1例。18例患者均患有屈光不正,其中4例诊断为弱视。15例患者伴多器官系统畸形,以舌咽(14例)和肢体发育异常(5例)为主,7例患者存在运动发育迟缓。9例患者存在孕期不良因素暴露。在17例行MRI检查的患者中,双侧展神经发育不良15例,单侧展神经发育不良2例;双侧面神经发育不良14例,左侧面神经发育不良3例;部分患者伴有其他颅神经发育不良,以舌咽神经、舌下神经为主。全外显子组测序及生物信息学分析未发现明确致病基因变异。结论MBS的核心临床特征为先天性眼球外转受限和面瘫,但临床表现多样且严重程度存在较大变异。所有行颅神经MRI检查的患者均存在展神经及面神经纤细或缺如,颅神经MRI检查结果可作为MBS诊断标准的补充。MBS的致病基因突变检出率较低,半数患者存在孕期不良因素暴露,提示MBS存在多因素致病机制。
简介:摘要目的:探究高糖诱导体外培养的视网膜Müller细胞自噬及凋亡的变化。方法:实验研究。将体外培养的SD大鼠视网膜Müller细胞根据不同糖浓度分为5.5 mmol/L葡萄糖组(正常组)及20、30、40、50 mmol/L高糖组,并对40 mmol/L高糖处理Müller细胞组采用不同时间3、6、12、24、36 h进行培养。使用蛋白免疫印迹法及细胞免疫荧光检测自噬指标LC3Ⅰ/LC3Ⅱ、自噬信号通路P62、Beclin-1蛋白表达及细胞定位;使用透射电镜及GFP-LC3慢病毒转染观察自噬小体的形成情况;使用TUNEL实验检测细胞凋亡状态。不同组别间数据比较采用单因素方差分析。结果:正常组及20、30、40、50 mmol/L高糖组中Müller细胞质的Beclin-1、P62及LC3Ⅰ/LC3Ⅱ蛋白相对表达量总体比较,差异均有统计学意义(F=131.21,P=0.029;F=197.25,P=0.012;F=100.02,P=0.045),其中与正常组比较各浓度高糖组Müller细胞质内Beclin-1、LC3Ⅰ/LC3Ⅱ蛋白均明显降低(P<0.05),P62蛋白相对表达量明显增加(P<0.001)。正常组以及6、12、24、36 h高糖组中Müller细胞质的Beclin-1、P62及LC3Ⅰ/LC3Ⅱ蛋白相对表达量总体比较,差异均有统计学意义(F=98.46,P=0.015;F=109.48,P=0.004;F=99.27,P=0.032),其中6 h高糖组LC3Ⅰ/LC3Ⅱ、Beclin-1蛋白明显增加(P=0.002、0.015),12、24、36 h高糖组与正常组相比较LC3Ⅰ/LC3Ⅱ、Beclin-1蛋白均明显下降(P<0.05),P62蛋白明显增加(P<0.001)。正常组及6、24 h高糖组视网膜Müller细胞中GFP-LC3转染阳性颗粒、自噬小体相对数量组间总体差异有统计学意义(F=240.49,P=0.014;F=198.98,P=0.001),其中与正常组比较,6 h高糖组GFP-LC3转染阳性颗粒、自噬小体相对数量增加(P=0.002、0.029),24 h高糖组明显降低(P=0.019、0.036)。正常组及6、24 h高糖组及3MA组视网膜Müller细胞凋亡指数分别为3.14±1.01、15.34±3.87、25.82±4.96、24.79±4.01,总体比较差异有统计学意义(F=234.12,P=0.003),与正常组比较,6、24 h高糖组TUNEL阳性细胞增多(P=0.022、0.039),24 h高糖组与6 h高糖组比较TUNEL阳性细胞进一步增加(P=0.017)。结论:高糖诱导体外培养的视网膜Müller细胞早期自噬增加,细胞凋亡抑制,随着时间不断延长,高糖抑制自噬形成,增加细胞凋亡。高糖抑制自噬可能是促进Müller细胞凋亡的重要原因。