Effects of glutamine induced heat shock protein 70 overexpression on atrial fibrosis and connexin43 remodeling in isoprenaline-treated rats
10.3760/cma.j.issn.0253-3758.2013.04.014
- VernacularTitle:谷氨酰胺诱导热休克蛋白70高表达可抑制大鼠心房肌纤维化及缝隙连接蛋白43重构
- Author:
Hong-Gang BAO
1
;
Wei-Ze ZHANG
;
Ling MA
;
Tao LI
;
Fei WANG
;
Yong-Qing CHEN
Author Information
1. 第四军医大学西京医院心血管内科
- Keywords:
Heart atria;
Fibrosis;
Glutamine;
HSP70 heat-shock proteins;
Connexin 43
- From:
Chinese Journal of Cardiology
2013;41(4):320-326
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of glutamine (Gln) induced heat shock protein 70 (Hsp70) overexpression on atrial fibrosis and connexin43 remodeling in isoprenaline(ISO) treated rats and related mechanisms.Methods Forty male SD rats were randomly divided into five groups (n =8 each group):control group,DMSO group,ISO5 mg · kg-1 · d-1 group (Fibrosis group),ISO5 mg· kg-1 ·d-1 +Ala-Gln0.75 mg· kg-1 ·d-1 group(Intervention group) and ISO 5 mg·kg-1 ·d-1 +QUE 100 mg·kg-1 ·d-1 +Ala-Gln0.75 mg· kg-1 · d-1 +DMSO group(QUE group).Rats were killed after7 d.The Ang Ⅱ expression in myocardial tissue was detected by radioimmunoassay; myocardial fibrosis was observed by HE staining.Collagen volume fractions were quantified by Masson staining and as the indicators of atrial fibrosis.The expressions of Hsp70,p-JNK1/2/3,c-Jun and Cx43 were determined with immunohistochemical method.Results Ang Ⅱ content was similar between the control group[(68.51 ± 10.76) pg/L] and DMSO [(71.47±11.49) pg/L] group (P＞ 0.05),and significantly increased in fibrosis group[(211.25 ±49.49)pg/L],intervention group[(185.32 ± 54.85) pg/L] and QUE[(189.90 ± 42.12) pg/L] group (P ＜ 0.01 vs.control group).Atrial fibrosis was significantly higher in the fibrosis group [(29.485 ± 9.966)％] and QUE group[(25.060 ±8.581)％] but not in the intervention group[(7.861 ± 1.867)％]compared to control group [(6.842 ± 1.674) ％] and DMSO group [(7.108 ± 1.343) ％].The expression of Hsp70 was similar among the control group (0.160 ± 0.023),DMSO group (0.163 ± 0.022),fibrosis group(0.166 ±0.028) and QUE(0.168 ±0.027) group (P ＞0.05) while significantly upregulated in the intervention group (0.215 ± 0.018) (P ＜ 0.01 vs.control group).The expressions of p-JNK1/2/3 and c-Jun were similar between control group(0.151 ±0.016;0.163 ±0.022) and DMSO group(0.154 ±0.021 ;0.164 ± 0.024) (P ＞ 0.05),while significantly upregulated in fibrosis group (0.202 ± 0.025 ; 0.254 ± 0.044) and QU E group (0.196 ± 0.024 ; 0.251 ± 0.027) (P ＜ 0.01 vs.control group) but not in intervention group(0.160 ±0.025 ; 0.168 ±0.024) were not changed obviously(P ＞0.05 vs.control group).The content of Cx43 was similar between control group and DMSO group(0.231 ± 0.035 vs.0.220 ± 0.032,P ＞ 0.05),and was linearly distributed in intercalated disc of the cardiomyocytes,however,the content of Cx43 was significantly reduced(P ＜ 0.01)and the Cx43 distribution was disordered in fibrosis group(0.163 ± 0.013) and QUE group(0.165 ± 0.024),while these changes were not found in intervention group.Conclusion Glutamine could reduce the atrial fibrosis and Cx43 remodeling in isoprenaline-treated rats by up-regulating Hsp70 and inhibiting JNK signaling pathway activation through down-regulating p-JNK1/2/3 and c-Jun expression.
