Inhibiting activation of ERK1/2 pathway improves atrial fibrosis and connexin40 remodeling in rats
10. 3724/SP.J.1008.2012.00259
- Author:
Zhi-Gang WANG
1
Author Information
1. Department of Cardiology, The Second Affiliated Hospital of Lanzhou University
- Publication Type:Journal Article
- Keywords:
Atrial fibrillation;
Connexin 40 remodeling;
ERK1/2;
Fibrosis;
MEK1/2
- From:
Academic Journal of Second Military Medical University
2012;33(3):259-264
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of extracellular signal-regulated kinase l/2(ERKl/2) pathway inhibitor U0126 on isopreterenol(ISO)-induced atrial fibrosis and connexin 40 (Cx40) remodeling in rats. Methods Thirty-two male SD rats were evenly randomized into control group, DMSO group, ISO (5 mg/[kg • d])+DMSO group (fibrosis group), and ISO (5 mg/[kg • d]) + U0126 (0. 5 mg/[kg • d]) + DMSO group (U0126-treated group). The corresponding reagents were given to each group once a day and the rats were killed and the myocardial tissues were collected after 7 d. The Ang IJ contents in the myocardial tissues were measured by radioimmunoassay; H-E staining and Masson staining were applied to measure the degree of atrial fibrosis; p-MEKl/2, p-ERKl/2, and Cx40 were detected by immunohistochemistry method. Results (1) The contents of Ang IJ were similar between control group ([242. 133 ± 4. 870] ng/L) and DMSO ([239. 412 ± 1. 795] ng/L) group (P>0. 05). Compared with the above two groups, Ang IJ contents in fibrosis group ([500. 250 ± 8. 869] ng/L)and U0126-treated group([498. 695 ± 9. 340]ng/L) were significantly increased (P alKO. 01). (2) Control group and DMSO group had no atrial fibrosis; the degree of atrial fibrosis in U0126-treated group was significantly lower than that in the fibrosis group (P<0. 01). (3) p-MEKl/2 and p-ERKl/2 expressions were similar in control group and DMSO group (P>0. 05), and those in the fibrosis group were significantly increased compared with control group and DMSO group(P<0. 01); the expression in U0126-treated group was similar to those in the control group and DMSO group(P>0. 05), and was significantly decreased compared with the fibrosis group(P<0. 01). (4) The contents of Cx40 were similar between control group and DMSO group (P>0. 05), and Cx40 was distributed in myocardial cell intercalated disc in a linear manner. The content of Cx40 was significantly reduced (P<0. 01) in the fibrosis group compared with the control group and DMSO group, with Cx40 distributed in disorder. The content of Cx40 in U0126-treated group was similar to that in the control group and DMSO group(P>0. 05)and most of the Cx40 was linearly distributed in myocardial cell intercalated disc. Meanwhile, the reduce degree of Cx40 content in U0126-treated group was significantly decreased than that in the fibrosis group(P<0. 01), and some Cx40 was linearly distributed in myocardial cell intercalated disc. Conclusion Long-term Ang TJ elevation in myocardium may be involved in atrial fibrosis and Cx40 remodeling, and U0126 can efficiently improve atrial fibrosis and Cx40 remodeling by inhibiting the activation of ERK1/2 pathway.
