Effect Of Rapamycin On Stromal Cell-derived Factor-1 Alpha Expression And Migration Of Rat Vascular Smooth Muscle Cell

OBJECTIVE To investigate the anti-restenosis effect of rapamycin and it's effect on stromal cell-derived factor 1 alpha(SDF-1α).METHODS The animal models of rat carotid artery intimal hyperplasia was established with balloon injury. 20 twelve weeks old rats was randomly divided into two groups: baseline group (n = 10) and rapamycin treatment group (n = 10, 25 mg/kg Rapamycin). HE staining was used to observe vascular lesions. Immunochistochemistry staining was used to detect the expression of SDF-1αin lesions. The migration of smooth muscle cells induced by SDF-1αwas observed with transwell. The levlel of blood serum SDF-1αwas measured by ELISA, Proliferation of vascular smooth cells was measured by methyl thiazolyl tetrazolium(MTT)method, Effect of different concentration of rapamycin(0,1,10,100ng/ml) on serum induced migration of vascular smooth cells was tested by transwell, Measurement of SDF-1αin mRNA and protein level was done by RT-PCR and western blot respectively.RESULTS Intimal hyperplasia was obviously induced by balloon injury. SDF-1αexpressed highly in lesions and rapamycin significantly reduced the expression of SDF-1αin intimal hyperplasia. SDF-1αcan also induce the migration of smooth muscle cells with a concentration-dependent manner. The result of MTT showed that, rapamycin inhibted proliferation of VSMC with a concentration-dependent manner, all of the three concentration(1,10 and 100ng/ml) rapamycin reduced the number of VSMC signifantly(p<0.05 or p<0.01), all of the three concentration(1,10 and 100ng/ml) rapamycin inhibited the migration rate of VSMC signifantly(p<0.05 or p < 0.01), and concentration dependly, all of the three concentration(1,10 and 100μmol/ml) rapamycin remarkably reduced SDF-1αexpression both in mRNA and protein level(p<0.05 or p<0.01), When the concentration of rapamycin rised up to 100μmol/ml, SDF-1αexpression both in mRNA and protein level was almost completely reduced.CONCLUSIONS①Rapamycin inhibited intimal hyperplasia of balloon injury rat common carotid artery;②Rapamycin inhibited SDF-1αlevel both in neointimal and blood serum;③Rapamycin inhibited proliferation and migration of rat VSMC concentration dependly;④Rapamycin inhibited expression of SDF-1αboth in mRNA and protein level.