微囊化人类心房肽cDNA重组质粒转染细胞对实验性高血压大鼠肾组织学改变的影响  

Effects of Encapsulated Plasmid Recombining with hANP cDNA Transfected Cells on Morphological and Histological Characteristic of Experimental Hypertensive Rats

作　　者：幸浩洋[1] 陈立国[1] 肖静[1] 郭慧玲[1] 万朝敏[2] 王正荣[1] 

机构地区：[1]四川大学华西医学中心生物医学工程研究室,成都610041 [2]四川大学华西第二医院,成都610041

出　　处：《生物医学工程学杂志》2004年第4期541-545,共5页Journal of Biomedical Engineering

基　　金：国家自然科学基金资助项目 ( 3 0 0 70 2 78;3 9970 2 75 )

摘　　要：将重组有人类心房肽 (h ANP) c DNA的质粒转染入中国仓鼠卵巢 (CHO)细胞 ,然后将细胞包被在具有免疫隔离作用的聚己内酯 (PCL)微囊内形成微囊化转基因细胞 ,其后移植至两肾一夹 (2 K1C)的高血压大鼠腹腔内 ,检测其对高血压大鼠的血压以及肾组织学改变的影响。结果移植 2 d后 ,大鼠的血压上升水平明显不如对照组高 ;组织学和形态学方面 2 K1C高血压大鼠肾小球硬化、肾小囊损害、肾动脉肥厚程度均较对照组减轻。实验说明PCL 材料微囊化 h ANP c DNA质粒转染 CHO细胞并植入大鼠体内后 ,能产生和向囊外排出具有生物活性的h ANP,降低高血压大鼠血压 ,减轻高血压产生的并发症。此项研究结果提供了一条心房肽治疗高血压或心衰的基因治疗新途径。A technique based on release of the human atrial natriuretic peptide (hANP) from plasmid hANP cDNA transfected Chinese hamster ovary (CHO) cells encapsulated in polycaprolactone (PCL)-capsules was used for a potential therapeutic approach to hypertension or congestive heart failure (CHF). The plasmid combining with hANP cDNA was transfected into CHO cells,and then encapsulated plasmid hANP cDNAt ransfected CHO cells were implanted into two-kidney,one-clip (2K1C) hypertensive rats intraperitoneally. The morphological changes,histological changes were investigated after the implantation of PCL-capsules in 2K1C hypertensive rats. The results showed that the implantation of encapsulated hANP-producing cells caused a significant delay of blood pressure (BP) increase after the encapsulated cells being implanted in 2K1C hypertensive rats. These effects were reflected morphologically by an attenuation of the glomerular sclerotic lesions,tubular damage and renal arterial thickening,comparing with control group. The plasma levels of hANP in 2K1C rats implanted with the PCL-capsules containing hANP-producing cells were higher than that of the control rats. These results demonstrated the usefulness of encapsulated hANP gene transfected cells as a new tool for hANP gene delivery in studying renovascular hypertension and cardiovascular diseases,thus implying the potential of using gene transfected cells as therapeutic agents in the treatment of cardiovascular diseases.

关 键 词：心房肽 cDNA重组质粒 实验 高血压 大鼠 微囊化转基因细胞 基因治疗 

分 类 号：R544.1[医药卫生—心血管疾病] R394[医药卫生—内科学]