瑞舒伐他汀对心肌肥厚大鼠TLR4信号通路的影响

Effect of rosuvastatin on TLR4 signal pathway in rats with cardiac hypertrophy induced by pressure overload

目的研究瑞舒伐他汀(rosuvastatin,RSV)对压力负荷诱导心肌肥厚大鼠心肌中toll样受体4(TLR4)及其下游核转录因子NF-κB p65、IκBα、炎症因子TNF-α表达的影响。方法采用腹主动脉缩窄大鼠模型,♂Wistar大鼠随机分为假手术组(S)、模型组(M)、RSV给药组(R,10 mg·kg^(-1)·d^(-1))每组10只。行心脏超声学检查,采用RT-PCR、Western blot、免疫组化、ELISA等方法检测心肌组织中心肌肥大基因ANP及TLR4、NF-κB p65、IκBα、TNF-α的表达。将TLR4蛋白水平分别与ANP、NF-κB p65、TNF-α水平进行相关性分析。结果 M组与S组相比,心脏体积和心肌细胞横截面直径、ANP mRNA水平均明显增加(P<0.01),伴TLR4mRNA和蛋白、NF-κB p65及TNF-α的水平明显增加及IκBα蛋白水平减少(P<0.05)。RSV抑制心肌肥厚,下调心肌组织中TLR4mRNA和蛋白、NF-κB p65及TNF-α的表达及上调IκBα蛋白水平(P<0.05)。在M组和R组,TLR4蛋白水平分别与ANP、NF-κB p65、TNF-α水平呈正相关。结论 RSV抑制心脏压力负荷诱导的心肌肥厚的作用可能与其抑制TLR4信号系统有关。

Aim To study the influence of rosuvastatin on toll-like receptor 4 （ TLR4 ） , and its downstream nu-clear transcription factor NF-kappa B p65, IκBα, in-flammation factors TNF alpha in rats with myocardial hypertrophy induced by pressure overload .Methods Myocardial hypertrophy was induced by abdominal aor-tic constriction （ AAC ） .Male Wistar rats were divided into 3 groups（n=10）：① sham-operated rats（S）;②AAC rats（M）;③AAC＋rosuvastatin（10 mg· kg -1· d-1 ） rats.From 1 week pre-opertion to 4 weeks post-operation, three groups were performed by gavage ad-ministration with equal volume of rosuvastatin and vehi-cle.The rats underwent cardiac color Doppler exami-nation.The level of ANP,TLR4, NF-κB p65,IκBα, TNF-αmRNA and protein expression in myocardium＆nbsp;were detected by real-time PCR, Western blot, immu-nohistochemical and ELISA respectively .Results The sizes of heart and cardiomyocytes and the expression of ANP mRNA and TLR4 signaling molecules were signif-icantly increased in group M , which could be blocked by rosuvastatin .TLR4 protein was positively related to ANP, NF-κB p65 and TNF-αrespectively .Conclusion Rosuvastatin prevents cardiac hypertrophy induced by pressure overload , which is associated with its inhi-bition of TLR4, NF-κB and TNF-αin myocardium ex-pression .