[1]叶显朗,黄伟昌,郑彦涛,等.厄贝沙坦可减轻2型糖尿病db/db小鼠心肌组织的炎症反应[J].南方医科大学学报,2017,(04):505.
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厄贝沙坦可减轻2型糖尿病db/db小鼠心肌组织的炎症反应()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2017年04期
页码:
505
栏目:
出版日期:
2017-04-20

文章信息/Info

Title:
Irbesartan ameliorates cardiac inflammation in type 2 diabetic db/db mice
作者:
叶显朗黄伟昌郑彦涛梁莺龚望球杨翀邈刘斌
关键词:
厄贝沙坦糖尿病心肌病NF-кB炎症
Keywords:
irbesartan diabetic cardiomyopathy nuclear factor-κB inflammation
摘要:
目的探讨血管紧张素Ⅱ受体阻滞剂(ARB)厄贝沙坦对2型糖尿病db/db小鼠心肌组织炎症反应的保护作用及其心脏保 护机制。方法10周龄db/db小鼠随机分成模型组、厄贝沙坦治疗组50 mg/(kg·d),同窝出生的10周龄非糖尿病db/+小鼠充当 正常对照组。正常组,模型组灌服等体积生理盐水,厄贝沙坦治疗组灌服厄贝沙坦(溶于生理盐水),药物干预16周后,记录心脏 质量、体质量,测定空腹血糖、血甘油三酯、血总胆固醇含量,对心脏行HE染色、Western blot、免疫组化和qPCR检测。结果与 正常组db/+小鼠相比,模型组db/db小鼠发生了肥胖、高血糖、高血脂(P<0.01);心肌组织肌纤维排列紊乱,间质增多,炎症细胞 浸润;P-IкBα蛋白水平升高、IкBα蛋白水平降低,P-IкBα/IкBα升高(P<0.001);NF-кB(P65)活性增强,入核增加(P<0.001),且促炎 细胞因子白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)mRNA水平升高(P<0.01),这些异常均与糖尿病心肌组织炎症反应升高 有关。厄贝沙坦的慢性治疗改善心肌病理学变化,并改善了2型糖尿病db/db小鼠高血糖诱导的心肌组织炎症反应指标。结论厄 贝沙坦改善了2型糖尿病db/db小鼠心肌组织炎症反应,其机制可能与抑制心脏血管紧张素Ⅱ的作用和NF-кB信号通路有关。
Abstract:
Objective To investigate the protective effects of irbesartan against cardiac inflammation associated with diabetes and obesity in the db/db mouse model of type 2 diabetes and explore the underlying mechanisms. Methods Twenty- four 10-week-old diabetic db/db mice were equally randomized into irbesartan treatment (50 mg/kg per day) group and model group, using 12 nondiabetic littermates (db/+) as the controls, The mice were treated with irbesartan or saline vehicle for 16 consecutive weeks, after which the heart pathology was observed and the heart weight, body weight, and serum levels of fasting blood glucose (FBG), total cholesterol(TC), and triglycerides(TG) were measured. The expression of nuclear factor-kappaB (NF-κB) p65 in the myocardium was assessed with immunohistochemistry, the protein levels of P-IкBα ,IкBα and β-actin were analyzed with Western blotting, and the pro-inflammatory cytokines IL-6 and TNF-α mRNA were detected using quantitative real-time PCR (qPCR). Results Compared with db/+ mice, the saline-treated db/db mice developed obesity, hyperglycemia and hyperlipidemia (P<0.01). Histopathological examination of the heart tissue revealed inflammatory cell infiltration, increased myocardial interstitium and disorders of myocardial fiber arrangement. The diabetic mice showed increased P-IкBα and decreased IκBα protein levels, enhanced activity and expression of NF-κB in the hearts, and increased mRNA expression of IL-6 and TNF-α in the myocardium. These abnormalities were all associated with increased inflammatory response. Treatment with irbesartan improved the heart architecture and attenuated high glucose-induced inflammation in the diabetic mice. Conclusion Treatment with irbesartan attenuates cardiac inflammation in type 2 diabetic db/db mice, and this effect was probably associated with the suppression of cardiac angiotensin II and NF-κB signaling pathway.

相似文献/References:

[1]朱艳,沈洁,胡园园,等.糖尿病大鼠肾脏转化生长因子β1与α3、β1整合素的相关分析[J].南方医科大学学报,2011,(06):1059.
[2]马聪,卢学春,范利,等.厄贝沙坦调节EA.hy926细胞动脉粥样硬化相关炎症基因的表达水平[J].南方医科大学学报,2011,(11):1835.
[3]蔡迎迎,邹少洲,范存霞,等.Exendin-4通过调控Sirt1/PGC1α延缓糖尿病小鼠心肌损伤[J].南方医科大学学报,2018,(05):520.

更新日期/Last Update: 1900-01-01