RNA干扰治疗慢性心力衰竭大鼠的实验研究

目的利用RNA干扰(RNAi)技术抑制心力衰竭(心衰)大鼠受磷蛋白(PLN)mRNA的表达,改善心脏功能。方法选用SD大鼠40只,对照组7只;其余33只造心衰模型,存活21只,随机分为心衰组、rAAV2-phRi1组,rAAV2-phRi2组,每组7只;rAAV2-phRi导入后30天测定血流动力学,逆转录聚合酶链反应检测心肌PLN mRNA,定磷法测定肌浆网Ca2+-ATP酶(SERCA2a)活性。结果rAAV2-phRi导入30天时,与心衰组比较,rAAV2-phRi1及rAAV2-phRi2对PLN mRNA的抑制效率为85.32%和67.65%,SERCA2a活性增加了104%和74%,血流动力学显著改善(P<0.05),达到对照组水平(P>0.05);rAAV2-phRi1的抑制效率、对心功能的改善显著优于rAAV2-phRi2。结论体内水平上,RNAi能够抑制心衰大鼠PLN mRNA表达,改善心脏功能。

The research on RNA interference therapy for chronic heart failure rats

Objective To inhibit phospholamban(PLN) mRNA expression and improve cardiac function of heart failure(HF) rats by RNA interference(RNAi).Methods Forty SD rats were used.Of them,7 were control group and 33 received coarctation of abodominal aorta operation.Twenty-one operated rats survived and were randomly divided into HF,rAAV2-phRi1 and rAAV2-phRi2 groups(n=7 in each group).Thirty days after rAAV2-phRi was injected,PLN mRNA was detected by RT-PCR,SERCA2a activity and hemodynamic parameters were measured.Results On 30th day,compared with HF rats,rAAV2-phRi1 and rAAV2-phRi2 groups decreased PLN mRNA by(85.32%) and 67.65% and increased SERCA2a activity by 104% and 74% respectively.Hemodynamic indexes improved significantly(P<0.05) and reached those of control group((P>)0.05).rAAV2-phRi1 was superior to rAAV2-phRi2.Conclusions In vivo,RNAi can inhibit the expression of PLN mRNA and improve cardiac function.rAAV2-phRi1 was superior to rAAV2-phRi2.