RESUMEN
ObjectiveTo explore the mechanism of Jiawei Wendantang in preventing and treating diabetic atherosclerosis by observing the effect of this prescription on the nuclear factor-κB / NOD-like receptor protein 3(NF-κB/NLRP3) pathway and related inflammatory cytokines in rat model of diabetic atherosclerosis. MethodFifty-four SPF-grade rats were randomized into blank, model, atorvastatin (0.9 mg·kg-1·d-1), and high-, medium-, low-dose (18.2, 9.1, 4.55 g·kg-1·d-1, respectively) Jiawei Wendantang groups. The rats in other groups except the blank group were modeled for diabetic atherosclerosis by intraperitoneal injection of streptozotocin and feeding with a high-sugar high-fat diet, and those in the blank group were injected with an equal dose of citric acid buffer and fed with a regular diet. The drug administration lasted for 4 weeks, and the blood glucose level in the tail vein was measured every 6 days. After the last administration, the rats were anesthetized for sample collection. Enzyme-linked immunosorbent assay was employed to measure the serum levels of interleukin-18 (IL-18), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1). Western blot was employed to determine the relative protein levels of NF-κB p65, NLRP3, and ICAM-1 in the abdominal aorta. Real-time quantitative polymerase chain reaction was employed to determine the mRNA levels of NLRP3 and interleukin-1β (IL-1β) in the abdominal aorta. The pathological changes in the thoracic aorta were observed by hematoxylin-eosin staining. ResultCompared with the blank group, the model group showed elevated levels of IL-18, CRP, TNF-α, and ICAM-1 in the serum and blood glucose (P<0.05, P<0.01), up-regulated protein levels of NF-κB p65, NLRP3, and ICAM-1 (P<0.01), and up-regulated mRNA levels of NLRP3 and IL-1β (P<0.05). Compared with model group, Jiawei Wendantang lowered the levels of IL-18, CRP, TNF-α, ICAM-1 and blood glucose (P<0.05, P<0.01), down-regulated the protein levels of NF-κB p65, NLRP3, and ICAM-1 (P<0.01), and down-regulated the mRNA levels of NLRP3 and IL-1β (P<0.05, P<0.01). Moreover, Jiawei Wendantang alleviated the pathological injuries in the thoracic aorta. ConclusionJiawei Wendantang may modulate the NF-κB/NLRP3 signaling pathway to reduce the release and adhesion of inflammatory cytokines and regulate the blood glucose level to treat diabetic atherosclerosis.