NADPH oxidase inhibitor apocynin prevents atrial remodeling in alloxan-induced diabetic rabbits
NADPH oxidase inhibitor apocynin prevents atrial remodeling in alloxan-induced diabetic rabbits
复制标题
NADPH 氧化酶抑制剂罗布麻素可预防四氧嘧啶诱导的糖尿病兔的心房重构
DOI：
10.1016/j.ijcard.2016.07.132
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发表时间：
2016-10-15
影响因子：
3.5
通讯作者：
Li, Guangping
中科院分区：
文献类型：
--
作者：
Qiu, Jiuchun;Zhao, Jianping;Li, Guangping
目的：糖尿病（DM）是心房颤动（AF）的独立危险因素。方法：60只日本大耳白兔随机分为对照组（Control，n = 20）、四氧嘧啶糖尿病组（DM，n = 20）和夹竹桃素治疗糖尿病组（APO，n = 20）。APO组给予夹竹桃麻素15 mg/kg/d，连续8周。测定血清丙二醛（MDA）、超氧化物歧化酶（SOD）水平和左心房组织NADPH氧化酶（NOX）活性。离体兔心脏Langendorff灌注。评估心房有效不应期（AERP）、心房有效不应期离散度（AERPD）、心房传导时间（IACT）和房颤易感性。Masson三色染色评价心房间质纤维化。Western blot检测NF-κ B、TGF-β、p38、P-p38、JNK、P-JNK、ERK和P-ERK蛋白表达。与对照组相比，DM组AF诱发率明显升高（46/450 vs.5/450，P < 0.05），而夹竹桃苷组AF诱发率明显降低（46/450 vs.12/450，P < 0.05）。夹竹桃素还能减轻糖尿病兔心房结构重构。Western blot结果显示，夹竹桃麻素可抑制DM诱导的TGF-β、NF-κ B、P-p38、P-JNK、ERK和P-ERK蛋白表达。结论：夹竹桃麻素可抑制四氧嘧啶诱导的AF，减轻心房重构。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Objectives: 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-kappa B, TGF-beta, 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-beta, NF-kappa B, 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.