Experimental Study Of Anti-inflammatory And Anti-intimal Hyperplasia Effects Of P38MAPK Inhibitor CBS3830 In Arterialized Autogenous Vein Grafts In Rats

Objective To study the anti-inflammatory and anti-proliferative effects of the p38 MAPK inhibitor CBS3830 in arterialized autologous vein grafts in rats, to further explore the mechanism of the p38MAPK signaling pathway in vein graft arterialization and intimal hyperplasia and vein graft stenosis for preventing intimal hyperplasia and vein graft stenosis to provide a new way of the targeted therapies.Methods 50 SD rats were randomly divided into four groups: normal group (n = 10), sham-operated group (n = 10), control group (n = 10) and drug group (n = 20). The arterialized autogenous vein graft model was established by using a modified cuff technique.Taking blood samples at time points of 0h, 24h, 48h, 4d, 1w and 2w. Obtaining vascular specimes at time points of 0h, 1w, 2w and 4w. Enzyme-linked immunosorbent assay (ELSIA) was used to detect the serum levels of TNF-αand IL-1β. Immunohistochemical staining was used to detect the expression of proliferating cell nuclear antigen (PCNA) of vascular specimens each group. HE staining was used to detect the pathological changes of vascular intima each group.Results The serum levels of TNF-αof drug group ,which was maximum at 24h, showed gradual decline, a significant statistical difference than control group at 48h ~ 2w (p <0.01).Compared with the sham-operated group, the serum levels of TNF-αof drug group were statistically different (p <0.01). The serum levels of IL-1βof drug group which was maximum at 24h, showed gradual decline, a significant statistical difference than drug control groupat 48h ~ 4d (p <0.01).The serum levels of IL-1βof drug group which was minimum at 4d, increased again at 4d ~ 2w . Compared with the control group and sham-operated group ,the serum levels of IL-1βof drug group was statistically different (p <0.01). The levels of PCNA expression of drug group, which was 9 times that of the normal group at 1w ,was increased, reach to the peak at 2w, began to decline at 4w, were significantly lower than control group at all time points (p <0.01). The extent of pathological intimal hyperplasia of drug group showed was significantly lower than control group at each time point by HE staining observation.Conclusion p38MAPK inhibitor CBS3830 has a significant anti-inflammatory and anti-proliferative effect in arterial autogenous vein graft in rats. Activation of p38 MAPK system exists in autogenous vein grafts and it may become a new target for the therapy of stenosis after vein grafts.