抗VCAM-1靶向超声微泡对体外循环相关骨髓中性粒细胞释放的可逆性影响  

Reversible Ef ect of Anti-VCAM-1 Ultrasound-targeted Microbubbles on Extracorporeal Circulation Related Bone Marrow Neutrophil Releasing

作　　者：干昌平[1] 邱旭[1] 张静漪[2] 安琪[1] 石应康[1] 

机构地区：[1]四川大学华西医院心脏大血管外科,成都610041 [2]四川大学华西医院超声科,成都610041

出　　处：《中国胸心血管外科临床杂志》2015年第2期146-150,共5页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

基　　金：国家自然科学基金面上项目资助(81170234)~~

摘　　要：目的评价抗骨髓窦状内皮细胞表面的血管细胞粘附分子-1（vascular cell adhesion molecule-1,VCAM-1）靶向超声微泡减少体外循环相关炎症条件下骨髓中性粒细胞释放的有效性和可逆性。方法 36只SD雄性大鼠随机分为6组,每组6只,分别为抗体组（A组）、抗体＋超声组（AU组）、靶向微泡组（T组）、靶向微泡破裂组（TU组）、体外循环后血浆刺激对照组（MC组）和空白对照组（C组）,并建立股骨骨髓原位灌注模型进行灌注。C组进行4个周期的缓冲液灌注;其余各组各5个灌注周期,第1周期灌注缓冲液后,第2~5周期灌注大鼠体外循环后血浆。第2周期结束后,A组和AU组推注等量抗VCAM-1抗体,T组和TU组注入等量抗VCAM-1靶向超声微泡,AU组和TU组在第3周期灌注的同时,给予同样的高声压超声辐射。分别收集各组灌出液直至灌注结束,检测灌出液的中性粒细胞总数。结果在体外循环后血浆刺激模拟炎症条件下,A组和T组骨髓释放的中性粒细胞总数与MC组相比均明显减少,且T组中性粒细胞减少得更加显著,差异有统计学意义（P〈0.05）。经过超声辐射后,TU组骨髓中性粒细胞释放恢复,中性粒细胞总量相比T组差异有统计学意义（P〈0.05）;AU组与A组各周期灌出液中中性粒细胞总数差异无统计学意义（P〉0.05）。结论抗VCAM-1靶向超声微泡可以识别阻断骨髓窦状内皮细胞表达的VCAM-1,并与其配体结合,同时微泡在骨髓窦状内皮表面形成物理阻挡屏障,进一步有效减少中性粒细胞释放。通过高声压超声辐射击破微泡,其空化效应还可使VCAM-1与微泡表面抗体间的结合分离,骨髓窦状内皮恢复炎症条件下释放中性粒细胞的能力,实现了中性粒细胞释放的可控性。Objective To evaluate the efficacy and reversible effect of anti-VCAM-1 ultrasound-targeted microbubbles on extracorporeal circulation（ECC） related bone marrow neutrophil releasing. Methods Thirty-six male SD rats were randomly divided into 6 groups with 6 rats in each group, including an antibody group（group A）, antibody with ultrasound group（group AU）, targeted microbubble group（group T）, targeted microbubble rupture group（group TU）, post-ECC plasma simulation group（group MC） and control group（group C） after in situ perfusion model establishment. Rats in group C received buffer perfusion for 4 cycles, and rats in other groups received perfusion for 5 cycles. After buffer perfusion for the first cycle, post-ECC plasma was infused to each group from the second cycle to the fifth cycle in group MC, A, AU, T and TU. Rats in group A and AU received injection with anti-VCAM-1 antibodies, while rats in group T and TU were given anti-VCAM-1 targeted microbubbles after the second perfusion cycle. Same ultrasound radiation was given to group AU and TU in the third perfusion cycle. Neutrophil counts from perfusate were compared among the 6 groups. Results Under simulated inflammatory condition after ECC, compared with group MC, significant reduction of neutrophil count released from bone marrow was found in group A and T, especially in group T（P〈0.05）. After ultrasonic radiation, neutrophil mobilization recovered in group TU and its neutrophil count was significantly higher than that of group T（P〈0.05）. There was no significant difference in neutrophil count between group A and AU in each perfusion cycle（P〉0.05）. Conclusions Anti-VCAM-1 targeted microbubbles can block the binding of VCAM-1 and its ligand, and form a barrier on the surface of bone marrow sinusoids endothelium to inhibit neutrophils migrating and releasing. The binding of VCAM-1 and its ligand on microbubbles is separated by cavitation of disrupting microbubbles with ultrasound, and neutrophils recover the abili

关 键 词：体外循环 中性粒细胞 超声微泡 可控性 

分 类 号：R654.1[医药卫生—外科学]