他克莫司对大鼠心肌肥厚及TOLL受体4的影响

Effects of tacrolimus on cardiac hypertrophy and toll like receoptor 4 signaling pathway in myocardium

目的探讨他克莫司(FK506)对压力负荷性心肌肥厚的影响及机制。方法♂Wistar大鼠随机分为假手术组(S组)、模型组(M组)、FK506给药组(F组),每组10只。制造腹主动脉缩窄大鼠模型,F组术前3天到术后4周给予FK506(0.5 mg.kg-1.d-1)肌肉注射,其他组给予等剂量溶剂。行心脏超声学检查,并采用Real-time PCR、Westernblot、免疫荧光、ELISA等方法检测ANP、钙调神经素(calci-neurin,CaN)及Toll样受体4(Toll-like receptor 4,TLR4)系统相关信号蛋白的表达。结果 M组与S组相比,心脏体积及心肌细胞变大(P<0.01),伴有ANP、CaN mRNA水平明显升高和TLR4系统相关信号蛋白表达升高(均有P<0.05)。FK506抑制心脏体积及心肌细胞变大(P<0.05),下调ANP、CaN及TLR4系统相关信号蛋白表达水平(均有P<0.05)。结论 CaN信号系统在心肌肥厚中发挥重要作用;FK506可能通过CaN及TLR4信号系统抑制心肌肥厚。

Aim To explore the effect of tacrolimus （FKS06） on cardiac hypertrophy and TLR4 signaling pathway in myocardium. Methods Thirty male Wist- ar rats were randomly divided into three groups： sham- operation group （ S group ） , model group （ M group ） , and FKS06 group （F group ）. Model rats underwent constriction of abdominal aorta （AAC）. Rats from F group were conditioned with FK506 （0. 5 mg kg-1 body weight every day）from three days before AAC to four weeks after AAC by intramuscular injection. After transthoracic echocardiographic analysis, hearts were stored at -80℃ for real-time quantitative PCR, West- ern blot, immunofluorescence, and enzyme-linked im- munoadsordent assay （ELISA）. Results Both the size of heart and cardiomyocyte and the level of ANP, cal- cineurin （CaN） mRNA and TLR4 signaling molecules were increased （P 〈0.01; P 〈0.05） in M group, compared with S group. FK506 lowered heart and the cardiomyocytes size （P 〈 0. 05 ）, and inhibited expres- sion of ANP, CaN and TLR4 signaling molecules sig- nificantly. Conclusion CaN plays an important role in the progress of cardiac hypertrophy. FK506 may in- hibit AAC-induced cardiac hypertrophy by CaN and TLR4 signal systems.