【摘要】 目的:评价冠状动脉内导入裸人心钠素(hANF)质粒DNA(pCR3.hANF)的安全性和生物活性.方法:经冠状动脉造影导管,将4 mg的裸 pCR3.hANF(n=6)或 pCR3(对照组,n=6)注入犬的左冠状动脉.基因导入40天后,通过聚合酶链式反应和Southern杂交检测hANF mRNA在左心室肌、肝、肺、肾的表达情况,且采用放射性免疫测定法测定血浆ANF的水平.结果:pCR3.hANF组中,hANF mRNA在心室肌中得到了较高的表达(P<0.01),血浆ANF水平明显高于对照组(P<0.01),且未发现hANFmRNA在肝、肺、肾中表达(P>0.05).结论:经冠状动脉导入裸pCR3.hANF可能是一安全、有效的基因导入途径.更多还原

【Abstract】 AIM: To evaluate the safety and bioactivity of catheter-mediated intracoronary gene delivery of naked plasinid DNA encoding human atrial natriuretic factor (hANF). METHODS: hANF gene delivery was performed in 12 canines. For each canine, 4 mg of reconstructed naked plasmid DNA encoding hANF (pCR3. hANF, n = 6) or pCR3 ( n = 6, control) in 2 mL normal saline was injected into left coronary artery via a coronary angio-graphic catheter. The expression of hANF mRNA in left ventricular myocardium, liver, lung, and kidney was identified by reverse transcription polymerase chain reaction and Southern blot analysis 40 d after gene delivery. Plasma ANF levels were determined by radio-immunoassay. RESULTS: The naked pCR3.hANF caused significant expression of hANF mRNA in ventricular myocardium (P<0.01). No hANF mRNA was detected in distal tissues, including liver, lung, and kidney (P>0.05). ANF levels were significantly higher in pCR3. hANF group than those in control group. CONCLUSION: These facts firstly demonstrate that intracoronary delivery of naked pCR3. hANF is probably a safe and feasible method for gene delivery by which hANF gene can be expressed in ventricular myocardium effectively.更多还原