RGD肽类肿瘤靶向受体显像的研究现状及前景

RGD肽是一类含有精氨酸-甘氨酸-天冬氨酸(Arg-Gly-Asp)的小分子多肽,与整合素ανβ3受体有高度的选择性和亲和力.RGD肽与整合素ανβ3受体的特异性结合可介导多种病理生理过程的发生,尤其在肿瘤细胞的黏附、转移和肿瘤新生血管生成中起重要作用.因此,整合素ανβ3受体有望成为新型放射性药物的靶点,而放射性核素标记的RGD肽也可能成为潜在的肿瘤受体显像剂而应用于临床.本文对RGD肽类肿瘤靶向受体显像的研究现状及前景进行综述.     

Specific targeting and noninvasive magnetic resonance imaging of an asthma biomarker in the lung using polyethylene glycol functionalized magnetic nanocarriers

Simultaneous inhibition of IL4 and IL13 via the common receptor chain IL4Rα to block adequately their biologic effects presents a promising therapeutic approach to give the additional relief required for asthma patients. In this study, superparamagnetic iron oxide nanoparticles were conjugated with anti‐IL4Rα blocking antibodies via polyethylene glycol (PEG) polymers. The delivery of these blocking antibodies to the inflammatory sites in the lung via the developed nanocarriers was assessed using noninvasive free‐breathing pulmonary MRI. Biocompatibility assays confirmed the safety of the developed nanocarriers for pre‐clinical investigations. For all the investigated formulations, nanocarriers were found to be very stable at neutral pH. However, the stability noticeably decreased with the PEG length in acidic environment and thus the loaded antibodies were preferentially released. Immunofluorescence and fluorimetry assays confirmed the binding of the nanocarriers to the IL4Rα asthma biomarker. Pulmonary MRI performed using an ultra‐short echo time sequence allowed simultaneous noninvasive monitoring of inflammatory responses induced by ovalbumin challenge and tracking of the developed nanocarriers, which were found to colocalize with the inflammatory sites in the lung. Targeting of the developed nanocarriers to areas rich in IL4Rα positive inflammatory cells was confirmed using histological and flow cytometry analyses. The anti‐IL4Rα‐conjugated nanocarriers developed here have been confirmed to be efficient in targeting key inflammatory cells during chronic lung inflammation following intrapulmonary administration. Targeting efficiency was monitored using noninvasive MRI, allowing detection of the nanocarriers’ colocalizations with the inflammatory sites in the lung of ovalbumin‐challenged asthmatic mice. Copyright © 2015 John Wiley & Sons, Ltd.     

应变率显像及组织多普勒成像综合评价基因治疗慢性心肌缺血的实验研究

目的探讨应变率显像及组织多普勒显像检测基因转染治疗心肌缺血的价值。方法健康家猪16头,在冠状动脉左旋支放置Ameroid环建立慢性心肌缺血模型,4周后治疗组注射携带血管内皮生长因子B基因的重组腺病毒液,对照组注射磷酸盐缓冲液,治疗后4周取心肌进行病理学检查。观察术前、置环后2周、4周及治疗后2周、4周左心室乳头肌水平短轴观后壁心肌收缩期速度(VS)、舒张早期速度(VE)、舒张晚期速度(VA)和内、外膜速度跨壁梯度的变化。结果缺血心肌较正常心肌速度梯度减小,色彩变暗。置环后2周,左室侧后壁心肌运动速度VS、VE较术前略下降但无统计学意义,局部心肌内、外膜速度跨壁梯度则明显降低(P<0.05);置环后4周,侧后壁心肌变薄,VS、VE明显减低(P<0.05),心肌内、外膜速度跨壁梯度进一步下降(P<0.05)。治疗后2周,基因转染组较对照组心肌运动速度无显著差异,而心肌内、外膜下速度跨壁梯度明显改善(P<0.05);治疗后4周,治疗组左心室侧后壁心肌运动速度较对照组增加(P<0.05),内、外膜下速度跨壁梯度持续改善(P<0.05)。结论心内、外膜速度跨壁梯度及心肌运动速度可准确评价慢性缺血心肌基因治疗前后节段性室壁厚度变化速率和室壁运动改善的情况,前者评价局部心功能的敏感性优于后者。     

多功能靶向纳米载体的制备及其对神经母细胞瘤的靶向性和MRI示踪性观察

目的 制备集靶向siRNA传递及MRI显像功能于一体的多功能靶向纳米载体,并验证其对神经母细胞瘤的靶向性及MRI示踪性.方法 制备PEG-PEI-SPION,scAbGD2 -PEG-PEI-SPION并检测其基本特性.利用凝胶阻滞检测纳米载体与siRNA的复合能力;以CLSM及MRI验证纳米载体的靶向性.结果 PEG-PEI-SPION,scAbGD2-PEG-PEI-SPION平均粒径分别为(60.0±2.3)nm及(90.0±7.8)nm.氮磷比(N/P)≥2.2时siRNA与PEG-PEI-SPION,scAbGD2 -PEG-PEI-SPION完全复合.CLSM实验及MRI结果证实scAbGD2-PEG-PEI-SPION具有靶向性.结论 scAbGD2-PEG-PEI-SPION对神经母细胞瘤具有靶向传递siRNA及MRI显影的功能.     

靶向性超声显影评价不同程度肝损伤的初步实验研究

目的 使用靶向超声分子显像对比分析大鼠不同程度急性肝损伤后峰值回声强度的改变与去唾液酸糖蛋白受体（ASGPR）的含量及血清学检查的关系.方法 根据腹腔灌注四氯化碳分析纯的不同剂量（10%、20%、30%、40%、50%）,将45只健康雄性SD大鼠随机分为相应5组（组Ⅰ~组Ⅴ）,每组9只,每组中再随机抽取4只取肝组织,分别检测ASGPR的含量;另5只仅常规麻醉,胸腹部备皮,经尾静脉团注靶向液态氟碳纳米脂质超声造影剂.从注射开始至0.5 h内连续观察并记录,0.5～1 h内每10 min观察并记录,1 h至造影剂消退每30 min观察并记录肝实质超声图像.DFY型超声图像定量分析诊断仪对各时间点采集到的超声图像进行分析.另选10只健康雄性SD大鼠作为靶向超声造影对照组,方法同前.结果 随着肝损伤程度的增加,肝组织内的ASGPR含量逐渐减少,且各组样本均数两两比较差异均有统计学意义（P〈0.05）.同时肝靶向超声造影后峰值回声强度逐渐降低,除对照组与组Ⅰ比较差异无统计学意义外,其余各组两两比较差异均有统计学意义（P〈0.05）,而达峰时间、峰值回声强度、造影前肝实质回声强度及清退后肝实质回声强度各组间比较差异均无统计学意义（P〉0.05）.结论 自制靶向肝实质细胞膜受体ASGPR的液态氟碳纳米超声造影剂的肝靶向性显影效果佳;不同程度肝损伤后的靶向超声显影结果改变与ASGPR结果改变一致,有利于超声显影定量评价肝脏功能.     

Targeting of lanthanide(III) chelates of DOTA‐type glycoconjugates to the hepatic asyaloglycoprotein receptor: cell internalization and animal imaging studies

The characterization of a new class of hydrophilic liver‐targeted agents for γ‐scintigraphy and MRI, consisting, respectively, of [¹⁵³Sm]³⁺ or Gd³⁺ complexes of DOTA monoamide or bisamide linked glycoconjugates (DOTA = 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid), is reported. In vitro studies show high uptake of radiolabeled [¹⁵³Sm]‐DOTAGal₂ by the human hepatocyte carcinoma cell line Hep G2 containing the asialoglycoprotein receptor (ASGP‐R), which is decreased to less than 50% by the presence of its high‐affinity ligand asialofetuin (ASF). In vivo biodistribution, γ‐imaging and pharmacokinetic studies on Wistar rats using the [¹⁵³Sm]³⁺‐labeled glycoconjugates show a high uptake in the receptor‐rich organ liver of the radiolabeled compounds containing terminal galactosyl groups, but very little uptake for those compounds with terminal glycosyl groups. Blocking the receptor in vivo reduced liver uptake by 90%, strongly suggesting that the liver uptake of these compounds is mediated by their binding to the asyaloglycoprotein receptor (ASGP‐R). This study also demonstrated that the valency increase improves the targeting capability of the glycoconjugates, which is also affected by their topology. However despite the specific liver uptake of the radiolabeled galactose‐bearing multivalent compounds, the animal MRI assessment of the corresponding Gd³⁺ chelates shows liver‐to‐kidney contrast effects which are not significantly better than those shown by GdDTPA. This probably results from the quick wash‐out from the liver of these highly hydrophilic complexes, before they can be sufficiently concentrated within the hepatocytes via receptor‐mediated endocytosis. Copyright © 2006 John Wiley & Sons, Ltd.     

超声斑点追踪显像技术评价高血压对左室心肌扭转-位移环的影响

5目的运用超声斑点追踪显像(STI)技术构建左室心肌扭转-径向位移环(Loop),探讨心动周期中高血压对心室扭转-位移环的影响并评价高血压患者左室功能的早期改变。方法原发性高血压患者32例和正常人24例,经胸采集心尖水平和心底水平二维图像,运用超声工作站行定量分析,构建左室心肌扭转-径向位移环(Loop),计算心肌扭转角度,径向位移。分析心动周期中扭转与径向位移之间的相关性,比较高血压患者与正常人的扭转峰值、二尖瓣开放时间点(MVO)扭转值、解旋率、收缩期和舒张早期径向位移,同时分析Loop各形态参数。结果①与正常人比较,高血压患者左室扭转峰值增大(18.26±4.2vs13.82±2.7,P<0.001),解旋率减小[(34±7.0)%/msvs(44±11.9)%/ms,P<0.001],差异均有统计学意义。②左室收缩期扭转与径向位移显著线性相关(r=0.97,P<0.05),高血压较正常组Loop收缩期斜率增大(P<0.05)。舒张早期心室解旋约40%,此期径向位移相对较小,二者呈线性相关(r=0.94,P<0.05),Loop图上舒张早期斜率较正常组大(P<0.05)。结论利用STI可以无创性的构建左室扭转-径向位移环。通过分析环的各形态参数,评估高血压患者早期左心功能变化。     

钆喷酸葡铵和不同b值对肝扩散加权成像的影响

目的探讨钆喷酸葡胺(Gd-DTPA)和不同b值对肝脏扩散加权成像(DWI)的影响。方法收集20例健康志愿者和61例临床怀疑肝肿瘤的患者,均行增强前、后两次DWI扫描,对比分析DWI图的信噪比(SNR)、对比信噪比(CNR)以及表观扩散系数(ADC)值。结果最终44例患者共56个病灶和20例正常肝志愿者纳入研究,分为正常肝组(20例),肝囊肿组(16个病灶),肝海绵状血管瘤组(14个病灶),肝细胞癌(HCC)组(15个病灶),肝转移瘤组(11个病灶)。相同b值下比较,增强前后两次DWI各组SNR值、CNR值差异均无统计学意义(P0.05),增强后DWI所得平均ADC值较增强前DWI所得平均ADC值有所减小,但其差异无统计学意义(P0.05)。不同b值下比较,增强后DWI各组的SNR值、CNR值差异均有统计学意义(P0.05),各值随b值的增大而减小;ADC值差异除肝囊肿组、转移瘤组无统计学意义(P0.05)外,其余组均有统计学差异(P0.05),且ADC值随b值增大而减小。结论钆对比剂Gd-DTPA对肝脏DWI图像质量和ADC值无显著影响,注射钆对比剂后5 min行肝DWI是可行的;在满足肝DWI图SNR和CNR的前提下,选择小b值有利于病灶的检出。     

扩散加权成像对肺癌的鉴别诊断及其放化疗疗效评价的研究进展

近年来肺部的MR成像,尤其是肺部DWI的研究被越来越多的学者所关注。很多学者发现DWI对肺内结节良恶性的鉴别有较高的价值,且可用于评价肺癌的放化疗疗效。本文针对DWI在肺癌的鉴别诊断与疗效评价方面进行综述。     

靶向血管内皮生长因子siRNA对K562细胞凋亡及survivin表达的影响

目的 应用腺病毒介导的血管内皮生长因子(VEGF) siRNA沉默K562细胞中VEGF的表达,观察其对K562细胞凋亡及凋亡抑制基因survivin表达的影响.方法 应用成功构建的携带特异性VEGF siRNA的重组腺病毒(Ad5-VEGF siRNA)感染K562细胞,实验分为3组:实验组(K562/Ad5-VEGF siRNA组)、空载体组(K562/Ad5组)、对照组(K562组).通过RT-PCR法检测细胞内VEGF及survivin mRNA的表达,ELISA法检测细胞培养上清中VEGF蛋白表达,Western blot法检测细胞survivin蛋白表达,流式细胞术检测细胞凋亡.结果 实验组细胞VEGF及survivin mRNA表达水平较对照组均有明显降低(P＜0.01),且细胞培养上清中VEGF蛋白表达水平[(1121±15)pg/ml]低于空载体组[(1290±28)pg/ml]和对照组[(1303±28)pg/ml](P＜0.01).Western blot法检测结果显示,实验组survivin蛋白表达水平(0.26 ± 0.11)较对照组(0.74±0.10)也显著降低(P＜0.01).实验组细胞凋亡率与对照组比较明显增加(P＜0.01).结论 应用RNA干扰沉默K562细胞中VEGF基因表达后,survivin的表达也随之降低,同时细胞凋亡率相应增加.VEGF可诱导K562细胞中survivin基因表达,可能是survivin基因表达的上游调控因子.     

内皮抑素基因对ACHN RCC细胞增殖和凋亡的影响

目的利用已构建的带有内皮抑素基因真核表达载体质粒导入裸鼠ACHN肾细胞癌（renal cell carcinoma,RCC）细胞中,研究内皮抑素基因对RCC细胞增殖和凋亡的影响。方法ACHN细胞浓度1×10^7个/L,经裸鼠右侧背部皮下注射0.2 ml,共注射24只裸鼠。荷瘤裸鼠随机分为3组,每组8只。治疗组：每只裸鼠瘤内3点注射复合物100μl（内含30μl梭华-SofastTM和30μg pSecES质粒）;对照组：每只裸鼠瘤内3点注射复合物100μl（内含30μl梭华-SofastTM和30μg pcDNA3.1质粒）;空白组：每只裸鼠瘤内3点注射生理盐水100μl。各组每只裸鼠间隔3 d注射1次,连续注射3次。以增殖细胞核抗原（PCNA）作为细胞增殖状态,按链霉亲和素生物素法（SABC）进行免疫组化染色。细胞凋亡检测用TUNEL法。结果内皮抑素真核表达质粒能显著抑制裸鼠ACHN RCC肿瘤体积增长,pSecES治疗组平均瘤重明显小于空白组和对照组（P〈0.01）,与空白组的肿瘤生长抑制率为34.48%,与对照组的肿瘤生长抑制率为40.68%。治疗组肿瘤细胞的凋亡指数（AI）明显高于对照组和空白组（P〈0.01）。pSecES治疗组肿瘤组织的AI/PI比值明显高于对照组和空白组（F=189.27,P〈0.05）。Spearman相关分析表明,肿瘤体积与细胞增殖之间无明显相关性（r=-0.041 2,P〉0.05）,肿瘤体积与细胞凋亡呈负相关（r=-0.734 6,P〈0.01）。结论内皮抑素基因治疗可使裸鼠ACHN RCC肿瘤细胞凋亡增加,肿瘤细胞的数量减少,在总体上表现为肿瘤的生长变慢、体积变小。     

组织多普勒成像评价心脏再同步化治疗对右心室功能和同步性的短期影响

目的 采用TDI评价心脏再同步化治疗(CRT)对右心室(RV)收缩功能和同步性的短期影响.方法 对51例因慢性心力衰竭(CHF)而接受CRT治疗的患者,于术前和术后1个月行常规超声心动图和TDI检查,检测右心室内径(RVD)、游离壁收缩期峰值速度(RVv)和同步性(RV-T),同时检测左心室收缩末期容积(LVESV)、射血分数(LVEF)和同步性(LV-TsD).以术后1个月LVESV减小率△LVESV≥15％为CRT治疗有效,比较术后与术前各参数的变化.结果 CRT术后38例患者(38/51,74.51％)为有效组,13例(13/51,25.49％)为无效组.两组术后RVD无变化,右心室收缩功能(RVv)和同步性(RV-T)均显著改善,RVv改善率与术前RVv和RV-T密切相关(r=0.69、-0.73,P＜0.05),而与LV-TsD无相关.结论 短期CRT即可显著改善右心室收缩功能和同步性.     

钆喷酸葡胺对肝实质及肝内常见恶性病变T2加权成像的影响

目的通过研究使用对比剂钆喷酸葡胺（Gd DTPA）增强前/后肝实质及肝内常见恶性病变T2WI信号的变化,探讨优化肝脏磁共振成像增强扫描流程的可能性。方法收集正常对照组89例和临床诊断明确的肝内常见恶性病变42例（其中肝癌19例、肝转移瘤23例）,增强前后分别行T2WI序列扫描,对T2WI信号变化进行测量对比分析。结果正常肝实质、原发性肝癌、肝内转移瘤增强后T2WI信号轻度减低,其差异存在统计学意义（P＜0.01）。对正常肝实质、肝癌、肝转移瘤3组间增强扫描前后T2WI信号差值进行对比,组间差异存在统计学意义（P＜0.05）;但信号下降百分比差异无统计学意义（P＞0.05）。增强前后对比,肝内常见恶性病变T2WI信号值与其周围正常肝实质T2WI信号差值差异无统计学意义（P＞0.05）。结论正常肝实质及肝内常见恶性病变因受对比剂影响,增强后T2WI强化程度减低,但对于肝内常见恶性病变的检出影响不大,从而说明增强后行MRI检查是可行的。     

实时三维超声和斑点追踪显像预测心脏再同步化治疗疗效的实验和临床研究

目的 应用实时三维超声心动图(RT-3DE)和斑点追踪显像(STI)评价左心室同步性,以探索检测心脏再同步化治疗(cardiac resynchronization therapy,CRT)疗效的有效方法。方法 动物实验对象为21条比格犬,随机分为A组(CRT组,10条),B组（心衰组,7条）和C组（对照组,4条）三组,临床研究对象为70例完成CRT术前及术后6个月随访的患者。以左室收缩末容积(LVESV)缩小15％为CRT治疗有效。评价同步性的超声参数包括RT-3DE评价左室16节段达最小收缩容积时间的标准差及其与心动周期的比值(Tmsv-16SD,SDI),STI评价犬左室乳头肌水平6节段QRS波起点至径向应变和圆周应变达峰时间的标准差与心动周期的比值(Trs-6SD、Tcs-6SD)。结果 动物实验的Tmsv-16SD、Trs-6SD、Tcs-6SD与左室射血分数(LVEF)呈负相关（r分别为-0.86、-0.75、-0.83,P均＜0.01）,Trs-6SD对CRT疗效最有预测价值,当Trs-6SD≥12.2％时,预测CRT有效的敏感性和特异性分别为83.3％和100％。临床研究显示,SDI最有预测价值,当其临界值为6.55％时,预测CRT有效的敏感性为80.0％,特异性为81.8％。结论 RT-3DE和STI能有效评价左室内不同步,有望成为预测CRT疗效的有效方法。     

CT脑灌注成像对脑梗死患者溶栓治疗前后脑血流动力学改变的评价

目的探讨CT脑灌注成像(CTP)评价脑梗死患者溶栓治疗前后脑血流动力学改变的价值。方法选择2008年10月至2010年12月收治的急性脑梗死患者29例,全部患者发病12 h内行颅脑CT及CTP检查,入院后29例患者均给予静脉溶栓治疗,治疗后1周内复查脑CT,两次CT检查图像均通过后期图像处理,去除颅骨、脑脊液影响,定义血管,减少噪声,得脑灌注参数图,测量脑血流量(CBF)、脑血容量(CBV),并进行前后定量比较。结果溶栓治疗前,CT检查发现12例存在脑梗死灶,CTP发现全部患者存在脑灌注异常区域,CBF、CBV减低。治疗后CT检查显示,缺血边缘区脑血流量较治疗前明显增加,治疗前后比较,差异有统计学意义(P<0.05);缺血中心区脑血流量与血容量与治疗前差异无统计学意义(P>0.05)。结论 CT脑灌注成像可以较好地显示脑梗死患者溶栓治疗前后脑缺血病灶血流情况,为评价治疗效果提供准确依据,值得应用。     

定量组织速度成像技术评价高血糖对2型糖尿病左室舒张期充盈模式的影响

目的探讨定量组织速度成像(QTVI)技术评价2型糖尿病左室舒张功能的临床价值.方法应用QTVI技术获取86例健康志愿者(NOR),77例糖尿病患者(DM)左室各室壁的房室瓣环、基底段、中段和心尖段的心肌组织运动曲线,测量其收缩期速度(Vs),舒张早期充盈速度(Ve),以及左房收缩期速度(Va),并将各室壁侧房室瓣环的收缩期和舒张期测值和Ve/Va比值平均.比较两组间二尖瓣环水平各个参数的差异性.以二尖瓣环Ve/Va<1,以二尖瓣口舒张期血流频谱E/A<1分别作为评判左室舒张功能异常的标准,比较两种方法对DM组左室舒张功能异常的检出率.根据空腹血糖(FPG)及糖化血红蛋白水平(HbA1C%)将糖尿病组进一步分为DM1组(n=35),DM2组 (n=42),比较两组间Ve/Va<1的室壁节段数.结果①糖尿病组二尖瓣环Ve/Va比值明显低于正常组(P<0.001).②QTVI法和多普勒血流频谱法对DM组左室舒张功能异常的检出率差异有显著性(P<0.001),而在正常组两种方法无显著性差异(P>0.05).③在DM1组中的Ve/Va<1的节段数明显少于DM2组(P<0.001).结论 QTVI能够准确定量评价糖尿病的左室舒张功能,并能敏感反映血糖水平对左室舒张功能的损害,为临床选择合理的治疗措施及对疗效的评判提供了定量指标.     

超声微泡介导转染FKBP12.6基因对小鼠H9c2(2-1)心肌细胞结构和功能的影响

目的探讨超声微泡介导转染FKBP12.6基因后小鼠H9c2(2-1)心肌细胞结构和功能的变化。方法将pcDNA3.1-FKBP12.6质粒与白蛋白包裹微泡造影剂混合,经超声转染H9c2(2-1)细胞后,通过倒置显微镜和透射电镜观察心肌细胞生长状况和超微结构的变化;荧光显微镜检测细胞内Ca2 浓度的变化;分别用RT-PCR、免疫组织化学检测mRNA、蛋白的表达。结果超声触发微泡破裂转染的FKBP12.6基因可在心肌细胞高效表达,细胞生长良好,蛋白合成活跃。高表达FKBP12.6的心肌细胞中,总的钙离子浓度增加。结论超声微泡介导FKBP12.6基因转染心肌细胞,可以明显改善心肌细胞的结构和功能。     

Effect of cellular and receptor activation on the extent of integrin αIIbβ3 internalization

Summary. Previous studies by our laboratory demonstrated that internalization of fibrinogen‐bound α_IIbβ₃ correlated with both a loss of aggregation and a loss of bound fibrinogen from the platelet surface. However, these studies do not address whether cellular activation, receptor activation and/or receptor occupancy are responsible for the observed internalization of α_IIbβ₃. The present studies were designed to evaluate the roles of cellular and receptor activation states on the α_IIbβ₃ internalization process. In these studies, washed platelets were allowed to bind FITC‐D57, an antiα_IIb monoclonal antibody, and were subsequently treated with ADP, thrombin receptor activation peptide (TRAP) or antiLIBS6 monoclonal antibody. Following flow cytometric analyses for log green fluorescence, rabbit antifluorescein was added, and the samples were re‐analyzed for residual/unquenched fluorescence. Because access of the quenching antibody is limited to extracellular/surface‐associated fluorescein, protection from quenching by antifluorescein is taken as evidence of internalization. Stimulation of platelets with ADP or TRAP resulted in a significant increase in the percent internalization of α_IIbβ₃ compared to control (8.7% and 12.8% vs. 2.9%). Addition of cytochalasin E prior to stimulation resulted in a greater than 90% inhibition of both TRAP and ADP‐induced internalization, suggesting that activation‐dependent internalization is mediated by the actin cytoskeleton. To investigate whether receptor activation increases the extent of α_IIbβ₃ internalization, platelets were treated with anti‐LIBS6, which directly activates α_IIbβ₃. Stimulation with anti‐LIBS6 caused an approximate 8‐fold increase in the extent of α_IIbβ₃ internalization. To evaluate whether the activated pool of α_IIbβ₃ is preferentially internalized, platelets were incubated with PAC‐1, an antibody specific for activated α_IIbβ₃. Platelets stimulated with TRAP, demonstrated a dose‐dependent internalization of PAC‐1. However, approximately 29% of total PAC‐1 binding was internalized, irrespective of TRAP concentration, suggesting that a constant proportion of activated α_IIbβ₃ is selectively internalized in platelets. Collectively, these data suggest that α_IIbβ₃ is internalized to a greater extent in activated platelets in a cytoskeleton‐dependent manner. Furthermore, the active conformer of α_IIbβ₃ is preferentially internalized which may act as a mechanism for downregulating adhesiveness of activated platelets in the circulation.     

背部弹力纤维瘤的多排螺旋CT及MRI诊断

目的探讨多排螺旋CT(multidetector spiral computed tomography,MSCT)及磁共振成像(magnetic resonance imaging,MRI)诊断背部弹力纤维瘤(elastofibroma dorsi,EFD)的影像学特点。材料与方法收集我院20例经手术病理证实的EFD患者资料,所有患者均行CT检查,其中8例行CT增强检查,4例行MRI检查,1例同时行MRI增强检查,3例MRI平扫检查,并分别测量EFD、前锯肌及周围脂肪CT平扫及增强后CT值进行比较,分析EFD的临床特点及CT、MRI表现。结果 20例患者中,13例病灶位于双侧,4例病灶位于右侧,3例病灶位于左侧,CT共发现33处病灶,并均位于背部肩胛下角肌肉深面,均呈扁丘状或半圆形肿块,主要以肌肉样密度为主,病灶内见条纹状脂肪密度沿病灶长轴间隔排列;病灶边缘毛糙不整,周围脂肪间隙模糊不清,CT增强扫描3例轻度强化,5例无强化;EFD与前锯肌、EFD与周围脂肪间平扫及增强CT值差异均存在统计学意义(P0.05);MRI平扫信号不均匀,呈等信号为主的肌组织与高信号的脂肪组织交错排列,MRI增强扫描1例呈不均匀中度强化。结论背部弹力纤维瘤具有典型的发病部位,根据CT及MRI影像表现均可做出明确诊断。     

组织多普勒超声评价交感神经阻滞对扩张型心肌病左心室心肌收缩力的影响

目的观察心交感神经阻滞对扩张型心肌病左心室心肌收缩力的影响。方法随机选取30例扩张型心肌病患者,分为对照组(16例)和治疗组(14例)。对照组给予常规抗心力衰竭治疗,治疗组在给予对照组治疗的同时,以0.5%利多卡因每2h经硬膜外导管推注一次(夜间睡眠除外),阻滞心区交感神经(胸1-5)。所有患者于治疗前和治疗后1个月行经胸心脏超声检查,测量左心房收缩末期内径(LAD),左心室舒张末期内径(LVEDd),短轴缩短率(FS),射血分数(EF),二尖瓣环后间隔、侧壁、前壁、下壁、前间隔、后壁的组织峰值收缩速度(Sm)和运动距离(D),计算6个位点的峰值收缩速度和运动距离平均值(MSm和MD),比较两组上述指标的差异。结果治疗组LAD和LVEDd均显著缩小,EF和FS明显增加,对照组上述指标无显著改善。同对照组比,治疗组MSm和MD均显著增加[MSm(4.91±0.56)cm/s对(4.09±0.82)cm/s,P<0.05;MD(0.61±0.18)cm对(0.41±0.18)cm,P<0.05]。左心室射血分数改善与MSm和MD的变化显著相关(MSmr=0.576,P=0.001;MDr=0.526,P=0.003)。结论对于扩张型心肌病,心区交感神经阻滞较常规治疗能显著缩小左心腔径,尤为突出的是它能更有力地增强心肌的收缩力,改善左心室收缩功能。