微囊化的人类心房肽cDNA质粒转染细胞对实验性高血压大鼠生理指标的影响  

EFFECTS OF ENCAPSULATED HUMAN ATRIAL NATRIURETIC PEPTIDE cDNA TRANSFECTED CELLS ON PHYSIOLOGICAL PARAMETERS OF EXPERIMENTAL HYPERTE NSIVE RATS

作　　者：陈立国[1] 肖静[2] 郭慧玲[2] 刘英辉[2] 万朝敏[3] 王正荣[2] 

机构地区：[1]天津市儿童医院检验科,天津300074 [2]四川大学华西医学中心生物医学工程教研室 [3]四川大学第二医院,成都610041

出　　处：《中国生物医学工程学报》2004年第4期321-328,共8页Chinese Journal of Biomedical Engineering

基　　金：国家自然科学基金资助(30070278;39970275)

摘　　要：目的:探讨微囊化人心房肽(hANP)基因转染细胞治疗高血压的新途径和新技术。方法:将重组有hANP基因(cDNA)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。移植微囊化hANPcDNA质粒转染细胞至两肾一夹(2K1C)的高血压大鼠腹腔内,检测其对高血压大鼠的血压以及多项生理指标的影响;同时研究微囊化hANPcDNA质粒转染细胞移植前后,2K1C高血压大鼠肾脏排泄的近日节律规律。结果:移植微囊化hANPcDNA质粒转染细胞至2K1C高血压大鼠腹腔内2周后,大鼠的血压上升水平明显不如对照组高,此作用至少持续5个月。在2K1C高血压大鼠体内,植入的微囊化转hANPcDNA质粒细胞可产生明显的利钠、利尿作用,且引起肾血流、肾小球滤过率、尿cGMP水平较对照组明显升高。此外,2K1C高血压大鼠的肾脏分泌的时间生物学特征研究显示:与对照组相比,植入微囊化hANPcDNA质粒转染细胞后,其近日节律的调整中值加大,振幅增高。结论:hANPcDNA质粒转染的CHO细胞通过植入高血压大鼠体内,可以降低高血压大鼠血压,将来可能适于植入人体。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。Objective: A technique based on the release of human atrial natriuretic peptide(hANP) from plasmid hANP cDNA transfected Chinese hamster ovary (CHO)cells encapsulated in polycaprolactone (PCL) -capsules was investigated for a potential therapeutic approach to hypertension. Methods: The plasmid hANP cDNA was transfected into CHO cells, then, encapsulated plasmid hANP cDNA transfected CHO cells were implanted into two-kidney, one-clip (2K1C) hypertensive rats intraperitoneally. The physiological parameter changes and the circadian rhythm of renal excretion were investigated post-implantation of PCL-capsules in 2K1C hypertensive rats. Results: The implantation of encapsulated hANP-producing cells caused a significant delay of blood pressure (BP) increase 2 weeks post-implantation and the effect lasted for more than 5 months in 2K1C hypertensive rats. The encapsulated hANP-producing cells also caused significant increases in renal blood flow (RBF), glomerular filtration rate (GFR), sodium output, urine excretion, urinary cGMP levels in 2K1C hypertensive rats comparing with the control rats. During a 12: 12 light-dark cycle, the implantation of the encapsulated hANP-producing cells increased the net excretion of water and caused an advance shift of the acrophases in 2K1C rats comparing with 2K1C rats implanted with encapsulated control CHO cells. Similarly, the implantation of encapsulated hANP-producing cells caused an increase in the net excretion of sodium, potassium and also reversed the delay shifts of acrophases caused by renovascular hypertension in 2K1C rats. Conclusion: This study demonstrated that the utilizing encapsulated hANP gene transfected cells mag be a new tool for hANP gene delivery in studying renovascular hypertension and cardiovascular diseases.

关 键 词：聚己内酯 心房肽 时间生物学 基因治疗 微囊化转基因细胞 

分 类 号：R331.31[医药卫生—人体生理学]