The Mediated Effect Of Pi3k-akt Signal Pathway On Type 2 Diabetes Mellitus Rats With The Susceptibility To Atrial Fibrillation

Background and Objective: Diabetes is an independent risk factor for atrial fibrillation, but the possible mechanism of this is not clear. For this study, we aim to investigate the possible mechanism of diabetic rats prone to myocardial structural remodeling and electrical remodeling and to clarify the correlation between diabetes and atrial fibrillation in the angle of signal pathway.Methods: Twenty-four 8-week-old male diabetic rats were randomly divided into 3 groups, each with 8 rats:① Group GK+IGF: the diabetic +PI3K agonist(IGF-1) group, 4 weeks before operation the diabetic rats were injected insulin like growth factor 1.5μg/kg through tail vein every day. ②Group GK+IGF+L-NAME: the diabetic +IGF-1+e NOS inhibitor(L-NAME), 4 weeks before operation the diabetic rats were injected L-NAME 1.5μg/kg through tail vein, and 30 min later was injected IGF-1 1.5μg/kg every day. ③Group GK: the diabetic rats group, the diabetic rats were injected equivalent physiological saline for 4 weeks. ④ WKY group: Eight homologous Kyoto Wister Rats as the control group, the rats were injected equivalent physiological saline for 4 weeks. After 4 weeks of drugs intervention, the left atrial(LA) diameter were examined by Color Doppler ultrasound. Detection of the atrial electrical parameters, including the P-wave duration, atrial effective refractory period(AERP) and its dispersion, atrial fibrillation rate and duration by atrial burst pacing using multiple physiological recorder. The myocardial cell size and morphology were observed by HE staining. The myocardial interstitial collagen volume fraction was calculated by Masson staining(CVF); the expression of PI3 K and e NOS in rat atrial muscle were detected by immunohistochemistry and Western blot.Results: 1. The histological examination showed that the atrial myocardial cell size in GK+IGF+L-NAME group and GK group were obviously increased and the range of cells was in disorder comparing to those of WKY group, and GK+IGF group were alike. 2. Masson staining showed that: GK group and GK+IGF+L-NAME group atrial interstitial fibrosis were more obvious than that of WKY group, GK+IGF group atrial interstitial fibrosis has just only a small amount of deposition. 3. The echocardiography results showed that: Compared with WKY group and GK+IGF group, left atrial diameter was obviously increased in GK group and GK+IGF+L-NAME group, but the difference was not statistically significant. 4. Western blot revealed that: the expression of PI3 K and p-e NOS protein in atrial myocytes of GK+IGF group and WKY group were significantly higher than those of GK group and GK+IGF+L-NAME group. 5. Electrophysiological examination showed that: Compared with WKY group and GK+IGF group, ⑴ The P-wave duration in GK group and GK+IGF+L-NAME group was prolonged obviously. ⑵ The PR interval in GK group and GK+IGF+L-NAME group was significantly increased. ⑶ The AERP dispersion of GK group and GK+IGF+L-NAME group increased significantly. ⑷ The incidence of AF and the AF duration in GK group and GK+IGF+L-NAME group were remarkably increased. ⑸ The AERP in all groups had no significant difference. ⑹ The P-wave duration, the PR interval and the AERP dispersion between the GK and WKY group、GK+IGF and GK+IGF+L-NAME group had no significant differences.Conclusions: 1. Atrial fibrillation susceptibility in rats with type 2 diabetes is higher, because of the structural remodeling and electrical remodeling of myocardium. 2. PI3K-Akt-e NOS signal pathway may be the important pathway to mediate atrial fibrillation in rats with diabetes mellitus.