title: [Effects of glutamine induced heat shock protein 70 overexpression on atrial fibrosis and connexin 43 remodeling in isoprenaline-treated rats].
abstract: OBJECTIVE
  To explore the effects of glutamine (Gln) induced heat shock protein 70(Hsp70) overexpression on atrial fibrosis and connexin 43 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, ISO 5 mg×kg(-1)×d(-1) group (Fibrosis group), ISO 5 mg×kg(-1)×d(-1) + Ala-Gln 0.75 mg×kg(-1)×d(-1) group (Intervention group) and ISO 5 mg×kg(-1)×d(-1) + QUE 100 mg× kg(-1)×d(-1) + Ala-Gln 0.75 mg×kg(-1)×d(-1) + DMSO group (QUE group).Rats were killed after 7 d. The AngII 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
  AngII 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 QUE 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Bao
authors.forename: Wei-Ze
authors.initials: WZ
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Ma
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Yong-Qing
authors.initials: YQ
authors.lastname: Chen
mesh_terms: D000818:Animals; D018031:Connexin 43 / Q000378:metabolism*; D005355:Fibrosis; D005786:Gene Expression Regulation; D005973:Glutamine / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006325:Heart Atria / Q000473:pathology; D007545:Isoproterenol / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018031:Connexin 43; D018840:HSP70 Heat-Shock Proteins; D016755:Proto-Oncogene Proteins c-jun; D005973:Glutamine; D007545:Isoproterenol