Effects of valsartan and U0126 on atrial fibrosis and connexin40 remodeling in rats
10.3760/cma.j.issn.0253-3758.2011.12.010
- VernacularTitle:缬沙坦与U0126对大鼠心房纤维化和缝隙连接蛋白40重构的影响
- Author:
Wei-Ze ZHANG
1
;
Zhi-Gang WANG
;
Yong-Qing CHEN
;
Ling MA
;
Tao LI
;
Hong-Gang BAO
;
Pei-Hong LI
Author Information
1. 兰州军区兰州总医院
- Keywords:
Valsartan;
Heart atria;
Fibrosis;
Connexins
- From:
Chinese Journal of Cardiology
2011;39(12):1129-1134
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of valsartan and MEK1/2 inhibitor U0126 on atrial fibrosis and connexin40 (Cx40) remodeling in rats treated with isopreterenol (ISO).Methods 32 male SD rats were randomly divided into control group (A),ISO (5 mg · kg-1 · d-1 for7 days) + DMSO group (B),ISO + U0126 (0.5 mg · kg-1 · d-1 for 28 days) group (C,U0126 was dissolved in DMSO),ISO +valsartan (30 mg · kg-1 · d-1 for 28 days) + DMSO group (D).Rats were sacrificed after 28 days.The AngⅡ content in myocardial tissue was measured by radioimmunoassay,P-MEK1/2,P-ERK1/2 and Cx40 was detected by immunohistochemistry,atrial fibrosis was determined on HE and Masson stained heart sections.Results The content of Ang Ⅱ was significantly higher in group B,C and D compared with group A [ (368.243 ±6.283 ) ng/L,( 357.175 ± 5.944 ) ng/L,( 359.908 ± 2.496 ) ng/L vs ( 250.380 ± 4.261 )ng/L,P ＜0.01 ] ; the degree of atrial fibrosis was significantly lower in group C and D compared with group B [CVF(10.260 ±0.525)％,(10.238 ±0.524)％ vs (78.710 ± 1.587)％,P＜0.01 ] while there was no atrial fibrosis in group A [ CVF(9.025 ± 0.456)％ ] ; the expression of P-MEK1/2 and P-ERK1/2 was significantly upregulated in group B compared with group A ( P-MEK1/2:0.311 ± 0.007 vs 0.203 ± 0.009,P ＜0.01 ; P-ERK1/2:0.259 ±0.003 vs 0.173 ±0.006,P ＜0.01 ) and significantly lower in group C and D compared with group B (P-MEK1/2:0.212 ± 0.004,0.213 ± 0.005 vs 0.311 ± 0.007,P ＜0.01,P-ERK1/2:0.178 ±0.004,0.175 ±0.007 vs 0.259 ±0.003,P ＜0.01 ).The content of Cx40 was obviously reduced and the distribution of Cx40 was disordered in group B compared with A (0.199 ±0.007 vs 0.241 ±0.004,P＜0.01) which could be partly reversed in group C and D ( 0.239 ±0.037,0.235 ±0.006 vs 0.199 ± 0.007,P ＜ 0.01 ).All parameters in group C and D were similar ( P ＞ 0.05 ).Conclusion The chronically elevated Ang Ⅱ content in myocardium may be related to atrial fibrosis and Cx40 remodeling in this model,valsartan and U0126 were equivalent on attenuating atrial fibrosis and Cx40 remodeling by inhibiting ERK pathways at different levels.
