Abstract: Objective To explore the protective effect and its mechanism of α-lipoic acid on high glucose-induced neonatal rat cardiac myocyte hypertrophy.Methods Apical myocardial cells of neonatal rats(1-3 days after the birth) were cultured for 48 hours with low glucose medium and then divided into a control group,a high glucose group(25.5 mmol/L),four α-lipoic acid groups(high sugar +50,100,200,300 mg/L alpha-lipoic acid),a protein kinase C(PKC) inhibitor group(high sugar+PKC inhibitor 50 nmol/L),and a nuclear transcription factor-κB(NF-κB) inhibitor group(high sugar+NF-κB inhibitor 5 mmol/L).The cells were cultured for 48 hours to detect cell surface area and protein content.PKC-α,NF-κB,tumor necrosis factor-α(TNF-α),and c-fos protein expression were detected with western blot.Results Compared with the control group,cardiac myocyte hypertrophy,increased cell surface area,increased protein content,increased PKC-α(0.89±0.03),NF-κB(0.88±0.14),c-fos(0.62±0.14),and TNF-α(0.85±0.05) in myocardial cells wee observed(P<0.01 for all).The treatment of α-lipoic acid resulted in cardiac myocyte hypertrophy,decrease of myocardial cell surface area and protein content(P<0.05 for all).Compared with those of high sugar group,intracellular PKC-α(0.50±0.07),NF-κB(0.24±0.03),TNF-α(0.39±0.05),and c-fos(0.15±0.06) protein expression were significantly decreased in the rats of 300 mg/L α-lipoic acid group(P<0.01 for all).Conclusion α-lipoic acid can inhibit cardiac myocyte hypertrophy induced by high glucose in neonatal rats and its mechanism may be related to the inhibition of the signal transduction pathway of PKC/NF-κB/TNF-α/c-fos.