PDGF signaling from pharyngeal pouches promotes arch artery morphogenesis

The great vessels of the heart originate from the pharyngeal arch arteries(PAAs).Anomalies of the PAAs often occur together with pharyngeal pouch malfo rmations,but the reasons for this phenomenon are not fully understood.In the current study,we show that platelet-derived growth factor(PDGF) signaling derived from the pharyngeal pouches plays an important function in PAA vasculogenesis,During PAA development in zebrafish embryos,pdgfaa and pdgfab are expressed in the developing pharyngeal pouches.Results from loss-of-function experiments revealed a critical role of these genes in PAA formation.We found that nitroreductase(NTR)-mediated pouch ablation distinctly decreased PDGF receptor tyrosine phosphorylation,yielding a severe loss of PAAs.Importantly,pouch-specific overexpression of pdgfaa in pdgfaa~(-/-);pdgfab~(-/-)mutants significantly relieved the PAA defects,which indicated a primary role of pharyngeal pouch-expressed PDGF ligands in signal activation and PAA morphogenesis.Our findings further showed that PDGF signaling was indispensable for the proliferation of PAA angioblasts.Together,these results established a role for PDGFaa-and PDGFab-mediated tissuetissue interaction during PAA development.     

冠心病患者心率变异性与冠状动脉病变狭窄范围及严重程度的关系研究

目的:探讨冠心病患者心率变异性(HRV)与冠状动脉病变狭窄范围及严重程度的关系。方法:选取上海市第十人民医院2015年1月至2018年7月期间收治的冠心病患者220例,所有患者均行冠脉造影及24 h动态心电图检查。按狭窄范围分为单支狭窄组(n=68)、双支狭窄组(n=82)、三支狭窄组(n=70),按狭窄严重程度分为轻度组(狭窄≤50%,n=62),中度组(50%狭窄70%,n=66),重度组(狭窄≥70%,n=92),另选取51例同期于我院体检的健康志愿者作为对照组。记录冠心病患者与对照组HRV各项指标,比较不同冠脉病变狭窄范围患者、不同狭窄严重程度患者正常平均N-N间期(SDNN)、正常相邻每5minR-R间期均数标准差(SDANN)、正常相邻正常N-N间期的均方根(RMSSD)、正常相邻间期差值高于50 ms心搏数占总心搏数的百分比(pNN50)、低频(LF)、高频(HF)及低频/高频比值(LF/HF)。结果:冠心病患者与对照组RMSSD、pNN50、LF、HF比较差异无统计学意义(P0.05),冠心病患者SDNN、SDANN低于对照组,LF/HF值高于对照组(P0.05)。不同冠脉狭窄范围、不同冠脉病变狭窄严重程度患者pNN50、LF、HF整体比较无统计学差异(P0.05),随着冠脉狭窄范围的增加或狭窄病变严重程度的加重SDDN、SDANN、RMSSD逐渐降低,LF/HF值逐渐升高(P0.05)。结论:HRV是评估心脏自主功能的良好指标,该指标中SDDN、SDANN、RMSSD、LF/HF值可作为评估冠心病患者冠状动脉的狭窄程度和狭窄范围的良好指标,具有重要的临床指导意义。     

Hyperlipidemic mice as a model for a real‐time in vivo detection of atherosclerosis by gold nanorods‐based diffusion reflection technique

Atherosclerosis (AS), the leading cause of morbidity and mortality in cardiovascular disease, needs an early detection for treatment and prevention of fatal events. Here, for the first time, we applied gold nanorods (GNRs)‐assisted diffusion reflection (DR), a noninvasive technique for in vivo detection of AS in a high‐fat‐diet‐induced c57bl mouse model, which resembles the manifestation of AS in humans. DR simply detects the change in light reflection profile of tissue due to the accumulation of GNRs in the AS plaques and enables clear detection of AS lesions in carotid and femoral arteries of these hyperlipidemic mice. After 24 hours post‐GNRs injection, DR showed the highest efficiency of AS detection. Moreover, the sensitivity of the DR method is much higher than computed tomography (CT) and is comparable to ex vivo high‐resolution CT. Our results strongly suggest that the DR method can detect early atherosclerotic lesions in a sensitive and specific manner.      

低氧对人肺动脉平滑肌和人肺动脉内皮细胞中HMGB1及相关炎症因子表达的影响*

目的:探讨低氧时人肺动脉平滑肌细胞(HPASMC)和人肺动脉内皮细胞(HPAEC)的高迁移率族蛋白1(HMGB1)及相关受体和炎症因子表达,并检测HMGB1对两种细胞增殖、迁移活性的影响。方法:低氧(1%氧浓度,Hypoxia组)及常氧(Control组)条件下培养HPASMC和HPAEC,RealTime-PCR检测两种细胞HMGB1、TLR2、TLR4、TLR9、RAGE、CD24、IL-6 、TNF-a和CXCL8 mRNA等受体和炎性因子的表达。MTS法观察不同浓度HMGB1对HPASMC和HPAEC增殖的影响;划痕法观察HMGB1对HPASMC和HPAEC迁移的影响。结果:Hypoxia组HPASMC、HPAEC中HMGB1及RAGE mRNA表达量较Control 组明显升高(P＜0.05及0.01);Hypoxia组HPAEC中CD24及HPASMC中IL-6 mRNA表达明显增高(P均＜0.05)。MTS结果显示在345 pmol/L 剂量下 HMGB1明显抑制HPAEC的增殖(P＜0.01),而对HPASMC增殖无影响。划痕实验示HMGB1对HPASMC和HPAEC迁移无明显影响。结论:低氧诱导HPAEC、HPASMC 产生HMGB1;HMGB1通过抑制HPAEC增殖引起内皮屏障功能障碍;而低氧进一步刺激HPASMC产生炎症因子。     

An in vivo mouse model of primary dysmenorrhea

Primary dysmenorrhea (PD) is a common gynecological disorder. Hitherto, animal models which recapitulate clinical features of PD have not been fully established. We aimed to examine whether a pain model in mice could mimic the clinic features of PD. After pretreated with estradiol benzoate (1 mg/kg/day) intraperitoneally (i.p.) for 3 consecutive days, non-pregnant female Imprinting Control Region mice (6–8 weeks old) was injected with 0.4 U of oxytocin to induce the stretching or writhing response which was recorded for a time period of 30 min. During the writhing period, the uterine artery blood flow alterations were examined by Doppler ultrasound detection. After writhing test, the uterine morphological changes were observed by hematoxylin and eosin (H&E) staining histopathology. In addition, enzyme-linked immunosorbent assay kit was used to measure the levels of prostaglandins F_2α/prostaglandins E₂ (PGF_2α/PGE₂) and TXB₂ (a metabolite of TXA₂)/6-keto-PGF_1α (a metabolite of PGI₂) in the uterine tissue homogenates and plasma, respectively. Western blot analyses were performed to determine the expressions of oxytocin receptor (OTR), beta2-adrenergic receptor (beta2-AR), and cyclooxygenase-2 (COX-2) in uterine, which are responsible for the uterine contraction. The writhing response only occurred in the estrogen pretreated female mice. The area of uterine myometrium significantly decreased along with the increased thickness in the oxytocin-induced estrogen pretreated mice model. The uterine artery blood flow velocity dropped, while the pulsatility index and resistance index slightly increased after the injection of oxytocin. The PGF_2α/PGE₂ level significantly increased and the plasma TXB₂/6-keto-PGF_1α level significantly enhanced. Compared with the control group, the uterine histopathology demonstrated moderate to severe edema of endometrium lamina propria. In consistent with the uterine morphological changes, a significant reduction of beta2-AR and a significant increase of OTR and COX-2 in the uterine tissue were observed. The writhing response was caused by the abnormal contraction of uterus. The uterine spasm and ischemia changes of oxytocin-induced estrogen pretreated female mice model were similar to the pathology of human PD. We reported an in vivo mice model, which can be used to study PD and for clinical therapeutic evaluations.     

痛风患者血管内皮功能及颈动脉粥样硬化的临床研究

目的:观察痛风患者氧化应激指标与颈动脉内膜中层厚度(IMT)的变化,探讨高尿酸引起内皮功能损伤和颈动脉粥样硬化的机制。方法:选择痛风患者123例,正常健康者116例,检测两组患者血尿酸、细胞间粘附分子1(ICAM-1)、内皮素-1(ET-1)、一氧化氮(NO)、纤溶酶原激活抑制剂-1(PAI-1)、收缩压、舒张压、空腹血糖、HDL-C、LDL-C、TC、TG等糖、脂代谢指标及颈动脉内膜中层厚度(IMT)。分析痛风患者内皮损伤相关因子水平和颈动脉IMT的关系。结果:痛风组血清细胞间粘附分子1(ICAM-1)、内皮素-1(ET-1)、纤溶酶原激活抑制剂-1(PAI-1)水平较对照组增高,颈动脉IMT明显增厚,NO水平较对照组降低,差异均有统计学意义(P0.05)。血尿酸水平、ICAM-1、ET-1、PAI-1与IMT密切相关(P0.01)。结论:痛风患者较对照组存在更明显的代谢紊乱,血管内皮功能损伤,更易发生动脉粥样硬化。     

17-AAG 对颈动脉球囊损伤大鼠血管平滑肌细胞增殖影响的实验研究

目的：研究17- 丙烯胺-17 去甲氧格尔德霉素（17-Allylamino-17-emethoxy-geldanamycin, 17-AAG）对球囊损伤后大鼠颈动脉 血管平滑肌细胞增殖的影响。方法：选取雄性Sprague-Dawley（SD）大鼠30 只,随机数字法分为球囊损伤（Balloon injury,BI）组10 只、球囊损伤+17-AAG 低剂量治疗（Balloon injury+Low dose AGG,BIL）组10 只、球囊损伤+17-AAG 高剂量治疗（Balloon injury+High dose AGG,BIH）组10只。建立大鼠颈动脉球囊损伤模型,病理学评估血管内膜增生情况。各组于球囊损伤28 天后取 材,将损伤区域的血管段取材固定,苏木精- 伊红染色（HE）观察血管并测量内膜面积（Intimal Area, IA）、中膜面积（Membrane Area,MA）,计算内膜/中膜面积比（IA/MA）,以评估内膜增生情况;同时,利用免疫荧光染色（Immunofluorescence staining, IFS）观 察增殖细胞核抗原（Proliferating cell nuclear antigen, PCNA）表达的情况,以评价血管平滑肌细胞的增殖情况。结果：大鼠颈动脉球 囊损伤模型成功建立。HE 染色后计算血管I/M比值,结果表明BIL组与BI组血管I/M 比值无统计学差异（P>0.05）,BIH 与BI组 血管I/M比值有统计学差异（P<0.05）。IFS结果表明,BIL组血管壁PCNA 表达较BI组略有降低,但无统计学意义（P>0.05）。BIH 组血管壁PCNA表达较BI组明显减低,有显著统计学差异（P<0.05）。结论：一定浓度的17-AAG可明显的抑制球囊损伤后颈动脉 血管平滑肌细胞增殖;17-AAG可以成为球囊损伤后大鼠血管平滑肌细胞增殖的抑制剂。     

阿托伐他汀钙对无动脉硬化原发性高血压患者血脂和颈动脉内膜中层厚度的影响

目的:研究阿托伐他汀钙对无动脉硬化原发性高血压患者血脂和颈动脉内膜中层厚度(cal MT)的影响。方法:选取2013年7月到2014年7月我院收治的无动脉硬化原发性高血压患者100例,按照随机数字表法将患者分为研究组和对照组,每组50例,对照组给予常规治疗,研究组在对照组的基础上给予阿托伐他汀钙治疗,治疗时间均为6个月。比较治疗前、治疗后两组血脂、血压以及cal MT。结果:研究组治疗后总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)显著降低,高密度脂蛋白胆固醇(HDL-C)显著增高,且显著优于对照组治疗后,比较差异具有统计学意义(P0.05);两组治疗后血压均显著低于治疗前,比较差异具有统计学意义(P0.05),且治疗后研究组显著优于对照组,比较差异具有统计学意义(P0.05);治疗后研究组cal MT显著优于治疗前,且优于对照组,比较差异具有统计学意义(P0.05)。结论:阿托伐他汀钙治疗无动脉硬化原发性高血压能显著改善患者血脂水平,降低其cal MT,对预防患者动脉粥样硬化具有重要意义。     

前列地尔对脑卒中冠状动脉旁路移植术神经系统影响研究

目的：分析前列地尔在脑卒中患者冠状动脉旁路移植(CABG)术后对患者神经系统并发症预防性的影响。方法：选取首都医 科大学附属安贞医院心外科六病区的收治脑卒中冠状动脉旁路移植术后患者60 例,随机分为两组,每组30 例患者,其中对照组 予常规肠外营养(PN)治疗,实验组加用前列地尔治疗。对比治疗前后两组患者神经系统功能及临床疗效。结果：①治疗后2 组患者 临床症状均有所减轻,实验组总有效率(100 %)率明显优于对照组(80.0 %),差异有显著的统计学意义（P＜0.05）;②治疗结束后, 实验组和对照组分别有4 例、9 例患者出现神经系统并发症状,实验组神经系统并发症的发生率为13.3 %明显低于对照组30 %, 差异有统计学意义（P＜0.05）。③经logistic 回归分析统计,术后神经系统并发症影响因素与性别无明显差异（P>0.05）,与颈动脉 重度狭窄、缺血缺氧性脑病以及脑卒中存在差异,有显著的统计学意义（P＜ 0.05）。结论：前列地尔注射液能有效的预防脑卒中患 者CABG术后预防神经系统并发症,对临床具有指导意义。