Effects of glutamine induced heat shock protein 70 overexpression on atrial fibrosis and connexin 43 remodeling in isoprenaline-treated rats / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>