Effects of course of diabetes mellitus on myocardial clock gene per2 and the mechanism

Abstract

Objective To explore the effect of diabetes on circadian expression of clock gene Per2 and its mechanism. Methods A total of fifty healthy adult male Sprague-Dawley rats were randomly divided into non-diabetic (NDM) group and DM group. The rats were randomly divided into 5 sub-groups: NDM+A, DM+A, NDM+P, DM+P and DM+A+PF (n=10 for each). At the same time, a circadian rhythm model was established and the rats were given 12 h light/12 h dark cycle environment. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of myocardium; Immunohistochemistry was used to analyze the pathological changes of myocardium and the expression of Per2; Real-time PCR was used to detect the gene expressions of CK1e and Per2, and Western blot was used to detect the expressions of CK1e and Per2 at the protein level. Single factor variance analysis and t-test were used for statistical analysis. Results Both CK1e and Per2 expressions increased at mRNA and protein levels in DM+A group than those in NDM+A group (t=2.84, 4.63; t=4.00, 5.32, respectively, all P<0.05); Compared with NDM+P group, the mRNA and protein expressions of CK1e increased in DM+P group (t=6.04, 3.60, all P<0.05), while the mRNA expression of Per2 decreased (t=3.90, P<0.05) and the protein expression of Per2 increased (t=2.55, P<0.05); Compared with NDM + A group, the protein expression of Per2 decreased in NDM + P group (t=3.54, P<0.05), while the mRNA expression of Per2 increased (t=5.35, P<0.05); Compared with DM+A group, the expressions of CK1e and Per2 at the mRNA and protein levels decreased in DM+P group (t=3.24, 4.32, all P<0.05); Compared with DM+A group, in PF-670462 intervention subgroup both CK1e and Per2 expressions at the protein levels decreased (both P<0.05); Compared with each NDM sub-groups, HE staining showed myocardial arrangement disorder, interstitial edema and inflammatory cell infiltration in each DM subgroups, and the results of immunohistochemistry showed more positive of Per2 expression displayed at diabetic myocardiopathy. Conclusion Diabetes mellitus affects the diurnal expression of clock gene Per2 injury possibly by upregulated CK1e signal which may be related to diabetic myocardial injury. Key words: Clock gene Per2; CK1e; Diabetes mellitus; Myocardial injury; Mechanism