Anti-proliferative effects of compound Danshen dripping pill (复方丹参滴丸) on rabbit aortic smooth muscle cells during the insulin resistance state

Objective: To study the anti-proliferative effects and possible mechanisms of compound Danshen dripping pill (复方丹参滴丸) on rabbit aortic smooth muscle cells during the insulin resistance state. Methods: The primary vascular smooth muscle cells (VSMCs) were cultured by planting rabbit thoracic smooth muscle pieces. The proliferation of VSMCs was induced by high concentrations of glucose and insulin. The rabbits were divided into following groups: a model group, a normal control group, treated groups including a pioglitazone (PIO) group, compound Danshen dripping pill (low, middle and high dose) subgroups and the various treated groups with respectively the addition of nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methylester (L-NAME) groups and L-NAME group. Cell proliferation was measured by methyl thiazolyl tetrazolium (MTT) assay, total NOS activities and nitrogen oxide (NO) content of VSMCs were determined by assay kits,respectively. Results: The proliferation of VSMCs was markedly induced by high concentrations of glucose and insulin, representing that the observation degree (A value) of the MTT soluble substance in VSMCs in the model group was higher than that of normal control group, but the total content and activity of NOS were lower than those of normal control group (all P0.01). Compared with the model group, the observation degree (A value) of MTT soluble substance in VSMCs was markedly decreased, and the total NOS activities and NO content of VSMCs were significantly increased in the PIO group, middle and high compound Danshen dripping pill groups, and the above effects could be partially blocked by NOS inhibitor L-NAME (P0.05 or P0.01); while there were no significant differences in above indexes in low compound Danshen dripping pill group (all P0.05). Conclusion: In the valid concentration range, compound Danshen dripping pill inhibits proliferation by involving in NO pathway in cultured VSMCs during the insulin resistance state.