ABSTRACT
Objective To evaluate the effects of geraniol(GOH) on neointima hyperplasia in rat carotid artery balloon injury model, and explore the potential molecular mechanisms associated with this effect. Methods Totally 20 male Sprague-Dawley (SD) rats were randomly divided into sham operation group (without balloon injury), control group (with balloon injury), low concentration group (with 50 mg/kg GOH intervention after balloon injury) and high concentration group (with 200 mg/kg GOH intervention after balloon injury). The intima to media (I/M) area ratio of neointima was measured by hematoxylin- eosin (HE) staining. The expression of proliferating cell nuclear antigen (PCNA) was measured by immunohistochemical staining at 14th day after operation. As the marker of oxidative stress, the levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) were measured by enzyme linked inmmnosorbent assay (ELISA). Results The I/M ratio, IOD, 8-OHdG and MDA values were increased in control group compared with those of sham group. The I/M ratio, IOD and 8-OHdG values were reduced in low concentration group compared with those of control group. But there was no significant difference in MDA level between low concentration group and control group. The I/M ratio, IOD, 8-OHdG and MDA values were significantly reduced in high concentration group compared with those of control group, which showed a more significant inhibitory effect than that of low concentration group (P<0.05). Conclusion GOH could attenuate balloon iniury induced neointima hyperplasia, which might be related to its effect on inhibiting expression of PCNA and decreasing oxidative stress.
ABSTRACT
Objective To explore the effects of fasudil on inhibiting vascular smooth muscle cells (VSMCs) proliferation in vitro,increasing cell apoptosis,and inhibiting the Ras-MEK 1/2-ERK 1/2 pathway.Methods Healthy male SD rats (80～100 g) were selected.VSMCs were separated by the thoracoabdominal aortic vascular membrane dissection.Cultured VSMCs were randomly divided into 5 groups:serum-free group; serum group; serum + 1 μmol/L fasudil intervention group; serum + 10 μmol/L fasudil intervention group; serum + 100 μmol/L fasudil intervention group.The proliferation and migration of VSMCs were detected by MTT method and wound healing assay.Cell cycle and apoptosis of VSMCs were examined by flow cytometric analysis.The mRNA expressions of pro-apoptotic protein (Bax) and anti-apoptotic protein(Bcl-2) were determined by RT-PCR method,and the ratio of Bax/Bcl 2 was calculated.Western blot were performed to detect the protein expressions of Ras,MEK1/2,ERK1/2 and Akt in VSMCs.Results Fasudil inhibited rat VSMCs proliferation and migration,and blocked FBS-induced progression from the G0/G1 phase to S phase in a dose-dependent manner.Fasudil inhibited the early and late apoptosis in VSMCs,increased Bax mRNA expression and inhibited Bcl 2 mRNA expression.Fasudil significantly inhibited the protein expressions of FBS-stimulated intracellular Ras,phosphorylated MEK1/2,ERK1/2 in a dosedependent manner,but did not affect the protein expression of phosphorylated Akt.Conclusions Fasudil can attenuate VMSCs proliferation by blocking Ras-MEK1/2-ERK1/2 pathway and increasing cell apoptosis.