Effects Of Simvastatin On The Expression Of PREN、PI3K、VEGF In Lung Tissue Of Rats With Pulmonary Fibrosis

Objective:To observe the effect of simvastatin on phosphase and tensin ho-mology (PTEN),Phosphatidyl inositol 3-kinase (PI3K),Vascular endothelial grow-th factor (VEGF) expression in bleomycin induced pulmonary fibrotic rats.To investigate the mechanisms of simvastatin’s antifibrotic effect.Methods:45 SD rats aged 6 weeks were randomly divided into 3 groups, wi-th each group 15 rats:Group A (normal control group), Group B (bleomycin group), Group C (simvastatin treated group). Rats of group B and C were intr-atracheal infusion with single dose of 5mg/kg bleomycin, while group A were intratracheal injected with equal volume of normal saline. The day after, group C rats were given lOmg/kg/d simvastatin suspension by intragastric injection, g roup A and B were given normal saline instead, at 7,14,28 days after mod-e ling,5 rats of each group were sacrificed, lung tissue of these rats was taken out for further study. The level of hydroxyproline was determined by alkalineh-ydrolysis; HE staining was used to see the degree of pulmonary fibrosis; imm-unohistochemistry was performed to detect PTEN, PI3K, VEGF; RNA was als-o isolated from lung of these sacrificed rats, and RT-PCR was performed to d-etermine the expression of these three genes.Results: (1) The content of hydroxyproline:compared with A group,B,C cont-ent of rats lung tissue in Hyp group significantly increased, which increased the most significant is the content of the 28 day,the difference was statistically sign-ificant; compared with B group, C group, Hyp content were lower, the difference was statistically significant. (2) Lung tissue pathology showed that lung tissue in group A rats was clear, no congestion, edema, exudates and no fibrotic le-sions was seen, while slight alveolitis, fibroblasts proliferation was seen in gro- up B on day 7; on the 14th day, alveolitis reached its peak, inflammatory cell-s infiltration aggravated significally; on the 28th day, there were obvious pulm-onary fibrosis, alveolar space collapsed or disappeared, hyperplasia of fiber was obvious, collagen deposition were visible. Compared to the group B, group C had a slighter alveolitis and fibrosis at each corresponding time point. (3)PTEN level in group B is obviously lower than group A at each time point, either j-udged by IHC or RT-PCR, the highest level of PTEN was shown in group C, the difference among these groups were statistically significant.PI3K,VEGF le-vels were significantly higher in group B than group A and C, group A rats had lowest expression of PI3K and VEGF compared to group B and C, the d-ifferences were statistically significant.Conclusion:The mechanisms of simvastatin against lung fibrosis may lie in promoting PTEN expression of fibrotic lungs while inhibiting PI3K and VEGF expression, suppressing pathological angiogenesis and early fibrosis.