超声激活血卟啉对活体兔心肌细胞凋亡和心功能影响的实验研究

目的 研究聚焦度超声激活血卟啉作用于活体兔心肌后,细胞凋亡,Bax、Bcl-2表达和血流动力学改变,为声动力用于心肌消融提供实验基础.方法 24只新西兰大白兔随机分为:假手术组(Sham),血卟啉(Hematoporphyrin,Hp)组,超声(Ultrasound,U)组,超声+血卟啉组(sonodynamic therapy,SDT).术前2 h,Hp和SDT组静脉给予2.5 mg/kg血卟啉.4组均行开胸手术,U组和SDT组于左室游离壁超声辐照1 min.术后第4 d,测量血流动力学参数,组织切片观察心肌细胞结构,原位末端标记(TUNEL)法检测细胞凋亡,免疫组化标记Bcl-2、Bax表达.结果 与U组比较,SDT组细胞坏死更明显,凋亡指数增加了34.7%(P<0.01).与对照组比较,U组和SDT组Bax 表达明显上调,而Bcl-2则下调(P<0.01).术后各组血流动力学参数无显著差异(P>0.05).结论 SDT有明显致心肌细胞坏死和凋亡效应,其凋亡机制与Bax表达上调 、Bcl-2表达下调相关.适当的SDT对心功能无明显影响,可能成为一种新型安全消融心肌的方法.     

超声激活血卟啉对肝癌细胞抗失巢凋亡的影响

目的 探讨超声激活声敏剂血卟啉对肝癌细胞株HepG2抗失巢凋亡的影响.方法 将HepG2细胞悬液随机分为4组:血卟啉组,培养液中加入血卟啉40μl孵育30 s;超声辐照组,以1.0 MHz、1.5 W/cm2超声辐照30 s;血卟啉与超声辐照组,同样方法予以血卟啉与超声联合处理;及空白对照组.各组处理后细胞一部分在软琼脂培养2周后观察其失巢生长能力,另一部分在铺有多聚羟乙基甲基丙烯酸树脂(polyhydroxy-ethylmethacrylate,poly-HEMA)的孔板中悬浮培养12 h后以Annexin V-FITC/PI双染法及24 h后以琼脂糖凝胶电泳检测其失巢凋亡情况.结果 血卟啉与超声辐照组HepG2细胞在软琼脂中不能形成集落,琼脂糖凝胶电泳显示出细胞凋亡特征性DNA ladder,其凋亡率为(14.89±2.82)%,与其余3组相比,差异均具有显著性.结论 血卟啉经超声激活后能抑制肝癌细胞株HepG2的抗失巢凋亡.     

超声评价兔活体心肌僵硬度的实验研究

目的探讨一种估算兔活体梗死心肌局部及整体的力学特性的方法。方法实验兔30只,随机分为梗死组和假手术组各15只,梗死组建立兔心肌梗死模型,采用二维超声结合心腔内压力的方法估算实时局部心肌僵硬度及心室腔僵硬度。结果局部心肌硬度缩舒系数（收缩末期硬度/舒张末期硬度）,梗死组较假手术组下降。梗死组压力-容积曲线右移,两组弹性常数k差异明显。结论二维超声结合心腔内压力的方法可以实时评价兔心肌的某些力学特性。     

Hematoporphyrin Monomethyl Ether Enhances the Killing Action of Ultrasound on Osteosarcoma In Vivo

Objectives. Osteosarcoma is one of the most common malignant cancers afflicting young adults. Ultrasound is a new therapeutic modality for controlling malignant cancers. Enhancing the efficacy of ultrasound treatment will improve clinical outcomes. The aim of this study was to investigate the killing action of ultrasound on osteosarcoma enhanced by hematoporphyrin monomethyl ether (HMME) in vivo. Methods. An animal model of an osteosarcoma xenograft was set up to investigate the inhibitory effect of sonoactivating HMME on osteosarcoma. High-performance liquid chromatography was used to analyze the time course of HMME in the osteosarcoma xenograft. Three hours after intravenous (IV) administration of HMME, ultrasound radiation was administered in the osteosarcoma xenograft. On day 7 after ultrasound radiation, the tumor volume and weight were measured and calculated for effect assessment, hematoxylin-eosin staining for histopathologic examination, immunohistochemical staining for proliferating cell nuclear antigen (PCNA) expression, and terminal deoxyuridine nick end-labeling (TUNEL) staining for apoptosis examinations. Results. The peak value of HMME in osteosarcoma tissues increased with time after IV administration of HMME and reached a plateau at 3 hours. The increasing rates of the tumor volume and weight in the control group were very fast, but the increasing rates in the ultrasound-alone group were slower, and those in the ultrasound-HMME group were the slowest throughout the observation period. There was a significant difference between the HMME-ultrasound, ultrasound-alone, and control groups (P < .01). Hematoxylin-eosin staining showed that some cells had typical cell death such as pyknosis and nuclear fragmentation after ultrasound radiation alone. More cells with pyknosis, nuclear fragmentation, and even karyolysis were found after HMME-ultrasound treatment. Immunohistochemical staining showed that the percentage of PCNA-positive cells decreased and that of TUNEL-positive cells increased after ultrasound treatment alone, and the changes in the PCNA- and TUNEL-positive percentages were significantly enhanced by pretreatment with HMME (20 mg/kg, IV) for 3 hours and ultrasound radiation (10.5 MHz) for 120 seconds at an intensity of 0.8 W/cm² (P < .05). Conclusions. Hematoporphyrin monomethyl ether pretreatment could substantially enhance the growth inhibition of ultrasound on osteosarcoma, which suggests that HMME is an efficient sonosensitizer, and ultrasound radiation with HMME could be developed as a new modality for treating osteosarcoma.     

超声微泡造影剂对心肌组织毛细血管通透性的影响实验研究

目的　研究超声破坏微泡造影剂对靶区内心肌组织毛细血管通透性的影响 ;探讨超声微泡造影剂增强基因转染的机制。方法　 2 4只健康雄性 Wistar大鼠 ,取 15只分为 3组 ,第 1组经静脉输入含有伊文思蓝 (Evans blue,EB)的微泡造影剂 ,并采用超声波在鼠胸壁辐照约 6 min破坏心肌组织内造影剂 ;第 2组采用超声照射 ,同时经静脉单纯输入 EB溶液 ;第 3组单纯经静脉输入 EB作为对照。照射完毕 2 h后放血处死大鼠 ,使用标准曲线和分光光度法测量各组大鼠心肌组织中 EB含量 (作为反映血管通透性的指标 )。另 9只大鼠随机分为 3组 ,每组 3只。第 1组经静脉输入微泡造影剂 ,并采用超声波在鼠胸壁辐照约 6 min破坏心肌组织内造影剂 ;第 2组单纯采用超声照射 ;第 3组不加任何处理 ,作为对照。照射完毕即刻处死大鼠 ,取心肌组织进行电镜观察毛细血管的改变。结果　采用超声照射 ,并经静脉输入微泡造影剂的大鼠 ,心肌组织中 EB含量为 (75 .33± 16 .80 )μg/ g,比单纯超声照射[(32 .2 1± 9.5 3)μg/ g]及心肌正常组织 EB含量 [(37.16± 7.98)μg/ g]明显增加 (P<0 .0 5 )。电镜结果显示超声破坏微泡后 ,能使毛细血管破裂 ,红细胞溢出于毛细血管外。结论　超声波触发破坏微泡造影剂后能使心肌组织毛细血管通透性增加 ,可     

高频超声导管消融活体犬心肌的实验研究

目的：本文探讨超声消融心室肌的可行性及作用特点。方法：用频率１０．４ＭＨｚ,外径７Ｆ的超声导管自开胸活体犬心外膜以不同时间和声强消融心肌,观察消融深度和形态结构特征;测量消融产生的温度变化。结果：消融深度与消融时间和声强呈良好相关,消融深度可达１０ｍｍ以上且边界清晰。当消融时间较长时,消融区近于圆形,而高声强短时间作用消融区呈椭圆形或矩形。消融中心温度可高达７８℃,而消融表面温度稍微增高。结论：超声可产生边清晰和深入的心肌消融,其消融深度和形状在一定程度上可控。提示超声可有效地消融心室肌深部病灶,为导管消融治疗室性快速心律提供新方法     

Effect of Overpressure on Acoustic Emissions and Treated Tissue Histology in ex Vivo Bulk Ultrasound Ablation

Bulk ultrasound ablation is a thermal therapy approach in which tissue is heated by unfocused or weakly focused sonication (average intensities on the order of 100 W/cm²) to achieve coagulative necrosis within a few minutes exposure time. Assessing the role of bubble activity, including acoustic cavitation and tissue vaporization, in bulk ultrasound ablation may help in making bulk ultrasound ablation safer and more effective for clinical applications. Here, two series of ex vivo ablation trials were conducted to investigate the role of bubble activity and tissue vaporization in bulk ultrasound ablation. Fresh bovine liver tissue was ablated with unfocused, continuous-wave ultrasound using ultrasound image-ablate arrays sonicating at 31 W/cm² (0.9 MPa amplitude) for either 20 min at a frequency of 3.1 MHz or 10 min at 4.8 MHz. Tissue specimens were maintained at a static overpressure of either 0.52 or 1.2 MPa to suppress bubble activity and tissue vaporization or at atmospheric pressure for control groups. A passive cavitation detector was used to record subharmonic (1.55 or 2.4 MHz), broadband (1.2–1.5 MHz) and low-frequency (5–20 kHz) acoustic emissions. Treated tissue was stained with 2% triphenyl tetrazolium chloride to evaluate thermal lesion dimensions. Subharmonic emissions were significantly reduced in overpressure groups compared with control groups. Correlations observed between acoustic emissions and lesion dimensions were significant and positive for the 3.1-MHz series, but significant and negative for the 4.8-MHz series. The results indicate that for bulk ultrasound ablation, where both acoustic cavitation and tissue vaporization are possible, bubble activity can enhance ablation in the absence of tissue vaporization, but can reduce thermal lesion dimensions in the presence of vaporization.     

高强度聚焦超声消融胰腺癌安全性及疗效研究

目的评估高强度聚焦超声（HIFU）消融胰腺肿瘤的安全性及疗效。方法应用Jc型体外HIFU肿瘤治疗系统治疗不能手术切除的胰腺癌，通过治疗前后的增强影像评估肿瘤的消融体积，探讨其与超声治疗参数之间的关系。结果20例HIFU治疗的胰腺癌有l6例获得治疗后的消融影像评估，肿瘤消融比率平均为（55．9±33．7）％，HIFU洽疗的最大声功率与肿瘤消融比率呈正相关（r=0．686，P=0．020），高声功率治疗组（最大声功率≥300W）获得的肿瘤消融比率[（68．5±26．1）％]显著大于低声功率治疗组（最大声功率≤280W）获得的消融比率[（32．5±31．8）％，P〈0．05]。15例治疗前显著疼痛的患者有12例治疗后疼痛缓解或显著减轻。本组1例高声功率HIFU治疗后发生了肠系膜上动脉闭塞。结论使用较高的声功率，体外HIFU治疗能够有效地消融胰腺肿瘤和缓解疼痛，作为晚期胰腺癌的减瘤治疗措施，其安全性和临床意义值得进一步研究。     

超声消融子宫腺肌病中期临床疗效

目的 探讨子宫腺肌病超声消融的临床疗效.方法 对78例以痛经为主、伴或不伴有经量增多的子宫腺肌病患者行超声消融治疗,定期随访症状并评分,增强MRI评价病灶消融情况.结果 78例中77例完成治疗,有完整随访资料者69例,每例患者至少随访18个月,平均24.2个月.62例痛经症状得到不同程度改善,总有效率89.9%,且症状持续缓解.治疗后痛经评分降低,与治疗前相比差异具有显著性(P< O.001).复发8例.60例增强MRI可见无灌注区域,消融发生率为87.0%,不同无灌注区范围情况下,患者临床疗效间的差异有统计学意义(P=O.004).结论 超声消融子宫腺肌病具有较好的中期疗效,可作为子宫腺肌病保守治疗的一种新方法.     

Thoracoscopic Radiofrequency Ablation of the Myocardium

Radiofrequency (RF) catheter ablation has been used for the treatment of ventricular tachycardia (VT), however, in some patients VT might result from subepicardiai macroreentry that could be successfully terminated by epicardial approach. This study examined the feasibility of thoracoscopic RF ablation of myocardium from epicardium using a custom made electrode. In five mongrel dogs, the thoracoscope was introduced through the 7th intercostal space. A 500-kHz continuous wave RF energy was connected to a custom made multiple electrode probe. Under thoracoscopic guidance, the heart was exposed and the RF probe was introduced. RF ablation was performed on the nonvascular ventricular wall of the beating heart. The left ventricular free wall and right ventricular outflow tract were satisfactorily visualized and ablated. The total dose of RF energy ranged from 50 to 500 J. and the estimated volume of ablated lesions ranged from 41.0–799 mm³. There were significant correlations between the RF discharge output and the irradiated lesion volume (P < 0.01), and the depth of the lesions (P < 0.01). Grossly, after RF ablation the ventricular myocardium demonstrated a circular, well-demarcated area of thermal injury. Volume and depth of the lesion depended upon the total dose of delivered RF energy. Thoracoscopic RF ablation appears to be a minimally invasive and useful method for creating irradiated myocardial lesions from epicardial surface. This method could he technically feasible for the treatment of Vts for which endocardial RF ablation is ineffective.     

超声造影剂增强HIFU消融作用的病理学研究

目的探讨超声造影剂增强高强度聚焦超声（HIFU）消融生物组织作用的病理学改变。 方法24只新西兰大白兔按体质量配对分为两组，A组肝脏接受单纯HIFU辐照，B组动物接受辐照前经静脉注射超声造影剂SonoVue。辐照后测量组织凝固体积并观察光电镜下组织学及细胞超微结构改变。 结果A组与B组组织凝固体积分别为（0．07±0．02）cm^3和（0．21±0．06）cm^3（P＜0．05）。光镜下两组辐照区肝组织未见凝固性坏死，B组可见部分细胞膜及胞核破坏。电镜下两组辐照区细胞内均未见完整细胞器，均呈现不可逆凝固性坏死，A组辐照区细胞结构较B组清楚。 结论超声造影剂增加HIFU焦域体积并进一步破坏细胞结构，从而增强HIFU消融作用。