Evaluation of renal ischemia-reperfusion injury in rabbits using microbubbles targeted to activated neutrophils
Evaluation of renal ischemia-reperfusion injury in rabbits using microbubbles targeted to activated neutrophils
复制标题
DOI：
10.1016/j.clinimag.2008.03.001
复制
发表时间：
2008-05-01
期刊：
影响因子：
2.1
通讯作者：
Zhang, Qun-xia
中科院分区：
文献类型：
--
作者：
Jing, Xiang-xiang;Wang, Zhi-gang;Zhang, Qun-xia
目的：本研究的目的是无创评估以活化中性粒细胞为靶点的微泡[磷脂酰丝氨酸偶联表面活性剂全氟丙烷填充微泡（SPMB-PS）]对兔肾缺血再灌注（I-R）损伤的严重程度。方法：将磷脂酰丝氨酸（PS）与自组装表面活性剂全氟丙烷填充微泡（SPMB）偶联制备靶向活化中性粒细胞微泡（SPMB-PS）。流式细胞术检测SPMB中PS的存在。建立18只家兔肾I-R损伤模型，进行超声造影检查。对12只家兔进行I-R损伤前后的SPMB- ps和SPMB超声检查。从选定的感兴趣区域生成时间强度曲线（TIC）。另外6只肾I-R损伤兔在静脉注射SPMB-PS后15 min行超声造影检查。立即切除肾组织进行免疫组化染色和髓过氧化物酶（MPO）活性分析。分析MPO活动与回波强度（VI）的相关性。结果：流式细胞术显示PS位于SPMB表面。TIC结果显示，正常肾注射SPMB- ps或SPMB时，达到最大VI的时间和微泡洗出所需的时间相同，但在I-R损伤后，SPMB- ps比SPMB明显延迟排空时间。注射SPMB- ps和SPMB后15min，正常肾脏VI无显著差异（P < 0.05），而明显升高（P < 0.05）
Objective: The objective of this study was to noninvasively evaluate the severity of renal ischemia-reperfusion (I-R) injury in rabbits with microbubbles targeted to activated neutrophils [phosphatidylserine-conjugated surfactant perfluoropropane-filled microbubbles (SPMB-PS)]. Methods: Microbubbles targeted to activated neutrophils (SPMB-PS) were prepared by conjugating phosphatidylserine (PS) to self-assembling surfactant perfluoropropane-filled microbubbles (SPMB). Flow cytometry was performed to assess the presence of PS in SPMB. A renal I-R injury model was established in 18 rabbits for contrast-enhanced ultrasonography. Examination of ultrasonography with SPMB-PS and SPMB was performed on 12 rabbits before and after I-R injury. The time-intensity curve (TIC) was generated from a selected region of interest. Another six rabbits with renal I-R injury underwent contrast-enhanced ultrasonography for 15 min after intravenous injection of SPMB-PS. The renal tissues were immediately excised for immunohistochemical staining and myeloperoxidase (MPO) activity analysis. The correlation between MPO activity and echo intensity (VI) was analyzed. Results: Flow cytometry demonstrated that PS was located on the surface of SPMB. TIC showed that the time at which the maximum VI was reached and the time needed for the microbubbles to wash out were the same in the normal kidneys injected with SPMB-PS or SPMB, while there was an obvious delay in emptying time with SPMB-PS compared with SPMB after I-R injury. Fifteen minutes after the injection of SPMB-PS and SPMB, VI was not remarkably different (P>.05) in the normal kidneys, while it was significantly higher (P