Smith Brendon W, Simpson Douglas G, Miller Rita J, Erdman John W, O'Brien William D
Bioacoustics Research Laboratory, Department of Electrical and Computer Engineering (B.W.S., R.J.M., W.D.O.), Division of Nutritional Sciences (B.W.S., J.W.E., W.D.O.), and Departments of Statistics (D.G.S.) and Food Science and Human Nutrition (J.W.E.), University of Illinois at Urbana-Champaign, Urbana, Illinois USA.
J Ultrasound Med. 2015 Jul;34(7):1209-16. doi: 10.7863/ultra.34.7.1209.
Diagnostic ultrasound imaging is enhanced by the use of circulating microbubble contrast agents (UCAs), but the interactions between ultrasound, UCAs, and vascular tissue are not fully understood. We hypothesized that ultrasound with a UCA would stress the vascular tissue and increase levels of heat shock protein 70 (Hsp70), a cellular stress protein.
Male New Zealand White rabbits (n = 32) were fed a standard chow diet (n = 4) or a 1% cholesterol, 10% fat, and 0.11% magnesium diet (n = 28). At 21 days, 24 rabbits on the cholesterol diet were either exposed to ultrasound (3.2-MHz f/3 transducer; 2.1 MPa; mechanical index, 1.17; 10 Hz pulse repetition frequency; 1.6 microseconds pulse duration; 2 minutes exposure duration at 4 sites along the aorta) with the UCA Definity (1× concentration, 1 mL/min; Lantheus Medical Imaging, North Billerica, MA) or sham exposed with a saline vehicle injection (n = 12 per group). Four rabbits on the cholesterol diet and 4 on the chow diet served as cage controls and were not exposed to ultrasound or restrained for blood sample collection. Animals were euthanized 24 hours after exposure, and aortas were quickly isolated and frozen in liquid nitrogen. Aorta lysates from the area of ultrasound exposure were analyzed for Hsp70 level by Western blot. Blood plasma was analyzed for cholesterol, Hsp70, and von Willebrand factor, a marker of endothelial function.
Plasma total cholesterol levels increased to an average of 705 mg/dL. Ultrasound did not affect plasma von Willebrand factor, plasma Hsp70, or aorta Hsp70. Restraint increased Hsp70 (P < .001, analysis of variance).
Restraint, but not ultrasound with the UCA or cholesterol feeding, significantly increased Hsp70.
循环微泡造影剂（UCA）的使用可增强诊断超声成像，但超声、UCA与血管组织之间的相互作用尚未完全明确。我们推测，使用UCA的超声会使血管组织受到应激，并增加细胞应激蛋白热休克蛋白70（Hsp70）的水平。
将雄性新西兰白兔（n = 32）分为两组，一组喂食标准饲料（n = 4），另一组喂食含1%胆固醇、10%脂肪和0.11%镁的饲料（n = 28）。21天后，对24只喂食胆固醇饲料的兔子进行如下处理：一组暴露于超声（3.2MHz f/3换能器；2.1MPa；机械指数，1.17；10Hz脉冲重复频率；1.6微秒脉冲持续时间；沿主动脉4个部位暴露2分钟），同时注射UCA Definity（1×浓度，1mL/min；Lantheus Medical Imaging，美国马萨诸塞州北比勒里卡）；另一组进行假暴露，注射生理盐水（每组n = 12）。4只喂食胆固醇饲料的兔子和4只喂食标准饲料的兔子作为笼养对照，不暴露于超声，也不进行采血约束。暴露24小时后对动物实施安乐死，迅速分离主动脉并在液氮中冷冻。通过蛋白质免疫印迹法分析超声暴露区域的主动脉裂解物中Hsp70的水平。分析血浆中的胆固醇、Hsp70以及内皮功能标志物血管性血友病因子。
血浆总胆固醇水平平均升高至705mg/dL。超声对血浆血管性血友病因子、血浆Hsp70或主动脉Hsp70均无影响。约束可增加Hsp70水平（方差分析，P <.001）。
显著增加Hsp70水平的是约束，而非使用UCA的超声或喂食胆固醇。
