NADPH oxidase inhibitor apocynin prevents atrial remodeling in alloxan-induced diabetic rabbits

详细信息    查看全文

• 作者：Jiuchun Qiu^a ; Jianping Zhao^a ; Jian Li^a ; Xue Liang^a ; Yajuan Yang^a ; Zhiwei Zhang^a ; Xiaowei Zhang^a ; Huaying Fu^a ; Panagiotis Korantzopoulos^b ; Tong Liu^a ; ^{liutongdoc@126.com" class="auth_mail" title="E-mail the corresponding author} ; Guangping Li^a ; ^{tjcardiol@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：NADPH oxidase ; Oxidative stress ; Apocynin ; Atrial remodeling ; Diabetes
• 刊名：International Journal of Cardiology
• 出版年：2016
• 出版时间：15 October 2016
• 年：2016
• 卷：221
• 期：Complete
• 页码：812-819
• 全文大小：3108 K

文摘

Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). The role of the NADPH oxidase (NOX) signaling in the setting of DM and the potential benefits of apocynin on diabetic atrial remodeling remain unknown.

Methods

Sixty Japanese rabbits were randomized into 3 groups as follows: Control group (Control, n = 20), alloxan-induced diabetic group (DM, n = 20) and apocynin-treated diabetic group (APO, n = 20). Rabbits in the APO group were orally administered apocynin (15 mg/kg/day) for 8 weeks. Serum malonaldehyde (MDA), superoxide dismutase (SOD) levels, and left atrial tissue NADPH oxidase (NOX) activities were measured. Isolated rabbit hearts were Langendorff perfused. Atrial refractory effective period (AERP), atrial effective refractory period dispersion (AERPD), interatrial conduction time (IACT) and vulnerability to AF were assessed. Atrial interstitial fibrosis was evaluated by Masson's trichrome staining. The protein expression of NF-κB, TGF-β, p38, P-p38, JNK, P-JNK, ERK and P-ERK was measured by Western blot analysis.

Results

There were no significant differences regarding SBP, DBP, LVEDP and AERP in the three groups. Compared with the Control group, AF inducibility was increased in the DM group (46/450 vs. 5/450, P < 0.05), and markedly reduced by apocynin (46/450 vs. 12/450, P < 0.05). Apocynin also attenuated atrial structural remodeling in diabetic rabbits. Western-blot analysis indicated that apocynin reduced the DM-induced increased protein expression of TGF-β, NF-κB, P-p38, P-JNK, ERK and P-ERK.

Conclusions

Apocynin, a NADPH oxidase inhibitor, prevents AF and attenuates atrial remodeling in alloxan-induced diabetic rabbits.