携galectin-7-siRNA超声纳泡靶向治疗大鼠心脏移植急性排斥反应的实验研究  

Experimental study of ultrasonic-targeted nanobubbles loading galectin-7-siRNA for inhibiting the acute rejection of rat transplantation hearts

作　　者：王卓[1] 赵冰冰[2] 李守强[1] 于丹丹[1] 赵晨[1] 姜双全[1] 冷晓萍[1] WANG Zhuo;ZHAO Bingbing;LI Shouqiang;YU Dandan;ZHAO Chen;JIANG Shuangquan;LENG Xiaoping(Department of Ultrasound Medicine,the Second Affiliated Hospital of Harbin Medical University,Harbin 150081,China)

机构地区：[1]哈尔滨医科大学附属第二医院超声医学科,哈尔滨市150081 [2]黑龙江中医药大学附属第二医院超声科

出　　处：《临床超声医学杂志》2020年第4期241-245,共5页Journal of Clinical Ultrasound in Medicine

基　　金：国家自然科学基金面上项目(81971626);国家自然科学基金青年科学基金项目(81701707);黑龙江省自然科学基金杰出青年项目(JQ2019H001)。

摘　　要：目的采用超声靶向微泡破坏技术介导galectin-7-siRNA转染,抑制大鼠移植心脏galectin-7表达,以达到靶向治疗心脏移植后急性排斥反应的目的。方法制备携galectin-7-siRNA的ICAM-1靶向纳泡;构建大鼠同系移植(ISO)及异系移植(ALLO)心脏模型,并分为4组:ISO+磷酸盐缓冲液(PBS)组、ALLO+PBS+低功率聚焦超声(LIFU)组、ALLO+微泡(NBs)组及ALLO+NBs+LIFU组。于移植后第1、3、5、7天分别行超声靶向微泡定位释放治疗,治疗后取材比较各组心脏galectin-7表达及急性排斥反应分级。结果制备的纳泡平均粒径(221.25±34.21)nm,平均电位(51.32±2.21)m V;galectin-7-siRNA携带率71.0%。ALLO+NBs+LIFU组galectin-7蛋白表达均低于ALLO+PBS+LIFU组和ALLO+NBs组(均P<0.05),ALLO+NBs+LIFU组急性排斥反应分级均明显低于ALLO+PBS+LIFU组及ALLO+NBs组(均P<0.05)。结论超声引导下携galectin-7-siRNA靶向微泡爆破治疗能降低大鼠移植心脏galectin-7表达,抑制急性排斥反应发生。Objective To inhibit the expression of galectin-7 and the occurrence of acute rejection after transplantation using galectin-7-siRNA-loaded nanobubbles combined with ultrasound-targeted microbubbles destruction(UTMD) technology.Methods The galectin-7-siRNA-loaded and targeted ICAM-1 nanobubbles were prepared and the rat heart transplantation model was constructed.Isograft(ISO) and Allograft(ALLO) of rat heart models were constructed and divided into 4 groups,including ISO+PBS group,ALLO+PBS+LIFU group,ALLO+NBs group and ALLO+NBs+LIFU group.UTMD were performed at 1,3,5,7 d after transplantation.In addition,the galectin-7 expression and acute rejection grading in each group of transplanted hearts were compared.Results The average particle size of NBs was(221.25±34.21)nm and the average potential was(51.32±2.21)mV.The carrying rate of galectin-7-siRNA was 71.0%.The expression of galectin-7 protein in the ALLO+NBs+LIFU group was lower than that in ALLO+PBS+LIFU group and ALLO+NBs group(both P<0.05),and the level of acute rejection was significantly lower in the ALLO+NBs+LIFU group than that in the ALLO+PBS+LIFU group and ALLO+NBs group(both P<0.05).Conclusion The galectin-7-siRNA-loaded targeted NBs combined with UTMD can reduce the expression of galectin-7 in the transplanted heart of rats and inhibit the occurrence of acute graft rejection.

关 键 词：超声 靶向纳泡 心脏移植 基因治疗 

分 类 号：R445.1[医药卫生—影像医学与核医学]