Expression Of Polyubiquitin And RC3 In The Common Carotid Artery Of Rats After Balloon Injury And Intervention Of Simvastatin

Objective To investigate the dynamic change of polyubiquitin and RC3 in the common carotid artery of rats after balloon injury and their effect on intimal proliferation. To evaluate the effect of Simvastatin on intimal proliferation and the expression of polyubiquitin and RC3 after balloon injury.Methods The 88 male SD rats were randomly divided into three groups: sham operation group(n=8),ballon injury group(n=48, including 1,4,7,14,21,28-days subgroup),Simvastatin administration group(n=32,including control subgroup,low- dose subgroup,middle-dose subgroup,high-dose subgroup).The balloon injury model of rat common carotid aortic artery was established.HE staining was used to observe the ratio of intima-media(I/M) thickness of the injured arteries with optical microscopy. The expression level of polyubiquitin and RC3 mRNA were examined with the method of RT-PCR. The expression level of polyubiquitin protein was examined with the method of immunohistochemistry.Results The intimal proliferation could be found in injured arteries and the intima-media ratio was found reaching the peak(2.31±0.43 vs control 0.02±0.005 ,P < 0.01)at 28th day.The level of polyubiquitin and RC3 mRNA was found increasing after balloon injury. The expression of polyubiquitin was observed to reach the peak at the 7th day(1.33±0.26 vs control 0.21±0.04,P <0.01),RC3 was observed to reach the peak at the 14th day (1.35±0.27 vs control 0.31±0.06,P <0.01). The expression of polyubiquitin protein was found increasing after balloon injury, the protein was observed to reach the peak at the 14th day(21.53±4.09 vs control 4.21±0.78,P < 0.01). The expression of polyubiquitin protein was correlated positively with intimal proliferation(r=0.827, P < 0.05).Simvastatin inhibited, in a dose-dependent manner, the intimal proliferation and the expression of polyubiquitin and RC3 mRNA and polyubiquitin protein. The intima-media ratio and the expression of polyubiquitin and RC3 mRNA and polyubiquitin protein was reduced by the high dose group(40mg·kg^-1·d^-1)by 50.22%,63.89%,60.29%和60.52%(P < 0.01),respectively.Conclusion The dynamic change of polyubiquitin and RC3 mRNA and polyubiquitin protein after balloon injury plays an important role in intimal proliferation. The expression of polyubiquitin and RC3 is concerned with intimal proliferation after balloon injury. The mechanism that Simvastatin suppressed intimal proliferation may involve the inhibitory effect on the expression of polyubiquitin and RC3.