Formononetin inhibits intimal hyperplasia and promotes vascular smooth muscle cell apoptosis in carotid balloon injury rats through regulating nf-kb signaling pathway

Objective: To investigate the effects of formononetin on intimal hyperplasia and apoptosis of vascular smooth muscle cells (VSMCs) in arterial injury rats. Material and methods: Rats were randomly divided into seven group: Sham operation group (Sham), model group (Model), low dose formononetin group (FOR-L), medium dose formononetin group (FOR-M), high dose formononetin group (FOR-H), atorvastatin group (ATO) and pyrrolidine dimethyl thiourea group (PDTC). Rats model with balloon-induced arterial injury were established and the carotid intima was observed by HE staining. Immunohistochemistry was used to detect the expression of PCNA protein in the vascular intima. TUNEL staining was used to measure the apoptosis of VSMCs. The expressions of apoptosis-related genes and NF-kappa B signaling pathway-related proteins in blood vessels were detected by RT-PCR and Western blot, respectively. The levels of MCP-1, TNF-alpha, 1L-1 beta and IL-6 in serum were measured by ELISA. Results: Compared with Model group, drug treatment significantly decreased the JIM ratio (P<0.05). In drug treatment groups, the expression of intracellular PCNA positive cells, Bcl-2 mRNA and p-P65 protein, and the contents of MCP-1, TNF-alpha, IL-1 beta and IL-6 were also decreased (P<0.05). However, compared with Model group, the apoptosis of VSMCs, the expression of Fas, Bax and Caspase-3 mRNA, and the level of p-I kappa B alpha protein in blood vessels were significantly increased in drug treatment groups (P<0.05). Conclusions: Formononetin can inhibit intimal hyperplasia and promote VSMCs apoptosis in carotid balloon injury ram and its mechanism is related to NF-kappa B signaling pathway.