Study on the Mechanism of Dihydroartemisinin in Vascular Remodeling by Inhibiting Inflammation

OBJECTIVE To explore the inhibitory effect of dihydroartemisinin on vascular remodeling by inhibiting inflammation. METHODS The patch method was used to culture mouse vascular smooth muscle cells(VSMCs), an in vitro smooth muscle cell proliferation model was established by TNF-α induction, a mouse femoral artery injury model was established by surgical deprivation of the artery, and dihydroartemisinin was used to interfere with cell and femoral artery injury in mice. The cell proliferation was detected by CCK-8 method, the pathological changes of femoral artery was evaluated by H&E staining and the thickness of media was measured, and the contents of IL-1β, TNF-α, IL-6, CCR8 in cells and IL-1β, TNF-α, IL-6, TGF-β1 in mouse femoral artery tissue were detected by ELISA method. The expression of NF-κB p65 and CCR8 in femoral artery tissue was detected by immunohistochemical method, and the expression of IL-1β, TNF-α, IL-6, IL-8, CCR8, NF-κB p65, TGF-β1 and MCP-1 mRNA in cells and femoral artery tissue was analyzed by qRT-PCR. Western blotting was used to analyze the expression of IL-1β, IL-6, TNF-α, IL-8, p-NF-κB p65, NF-κB p65, CCR8, TGF-β1, MCP-1 protein in cells and femoral artery tissue. RESULTS In the models of TNT-α-induced VSMCs proliferation and femoral artery injury of mice, the proliferation of VSMCs, the content of TNF-α and IL-6, the expression of IL-1β, IL-6, IL-8, NF-κB p65 and TGF-β1 mRNA were significantly increased, and the expression of IL-6, CCR8 and NF-κB p65 protein was significantly increased(P<0.05 or P<0.01). Dihydroartemisinin could significantly reduce the expression of IL-1β and IL-8 mRNA of VSMCs induced by TNF-α, and reduce the expression of IL-1β mRNA and IL-1β, p-NF-κB p65 protein of femoral artery injury in mice(P<0.05 or P<0.01). CONCLUSION Dihydroartemisinin can reduce vascular inflammation and delay remodeling of injured vessels, indicating that dihydroartemisinin can be used as a potential therapeutic drug for percutaneous coronary intervention(such as stent implantation).