Abstract: Objective To investigate the protective effect and its mechanism of ferulic acid on myocardial injury in type 2 diabetic db/db mice. Methods Twenty db/ db mice with type 2 diabetes were randomly divided into model group and ferulic acid group, and 10 normal db/ m mice were randomly selected as control group. The control group and model group were intragastrically given distilled water, and ferulic acid group was given ferulic acid (30 mg/kg) once a day. After 8 weeks of continuous administration, the serum levels of glucose (BG), creatine kinase (CK), creatine kinase isoenzyme (CKMB) and advanced glycation end products (AGEs) were measured. The morphological changes of myocardial tissues were observed by HE and Masson's staining. The mRNA expressions of TLR-4, NF-ĸB and NALP3 were determined by Q-PCR.Immunocytochemistry and Western blot assay were used to detect the expressions of TLR-4, NF-ĸB and NALP3 proteins.Results The body mass, heart mass and cardiac mass index were significantly higher in the model group than those in the control group. After ferulic acid intervention, the body mass, heart mass and heart mass index were significantly decreased compared with those of the model group (P＜0.05). In the model group, the myocardial cells were swollen and hypertrophy, and obvious fiber proliferation was found. After the intervention with ferulic acid, the swelling of cardiomyocytes and the proliferation of fibers were significantly alleviated. The expression levels of serum BG, CK, CK-MB and AGEs were significantly higher in the model group than those in the normal group. After treatment with ferulic acid, the serum levels of BG, CK, CK-MB and AGEs were decreased compared with those of model group (P＜0.05). The mRNA and protein expression levels of TLR-4, NF-ĸB and NALP3 were significantly higher in the model group than those in the control group.After ferulic acid intervention, the mRNA and protein expression levels of TLR-4, NF-ĸB and NALP3 were significantly decreased (P＜0.05). Conclusion Ferulic acid can improve blood glucose level and reduce myocardial cell injury and myocardial fibrosis in type 2 diabetic mice, which may be related to the inhibition of TLR-4/NF- ĸB signal pathway and inflammation.

Key words: FERULIC ACID, diabetes mellitus, type 2, diabetic cardiomyopathies, Toll-Like receptor 4, NF-kappa B, NACHT-LRR-PYD-containing protein 3