[1]陈 丹,吴基良,李 晶.内质网应激信号通路在高脂诱导的心肌细胞损伤中的作用[J].中国药理学通报,2017,(07):966-971.[doi:10.3969/j.issn.1001-1978.2017.07.016]
 CHEN Dan,WU Ji-liang,LI Jing.Role of endoplasmic reticulum stress in high fatty acid induced injury in cardiomyocytes[J].Chinese Pharmacological Bulletin,2017,(07):966-971.[doi:10.3969/j.issn.1001-1978.2017.07.016]
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内质网应激信号通路在高脂诱导的心肌细胞损伤中的作用()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2017年07期
页码:
966-971
栏目:
论著
出版日期:
2017-07-10

文章信息/Info

Title:
Role of endoplasmic reticulum stress in high fatty acid induced injury in cardiomyocytes
文章编号:
1001-1978(2017)07-0966-06
作者:
陈 丹1吴基良2李 晶2
1. 武汉大学中南医院心血管内科,湖北 武汉 430071;
2. 湖北科技学院糖尿病心脑血管病变湖北省重点实验室,湖北 咸宁 437100
Author(s):
CHEN Dan1 WU Ji-liang2 LI Jing2
1.Dept of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China;
2. Hubei Province Key Lab on Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning Hubei 437100, China
关键词:
内质网应激 高脂 棕榈酸 心肌损伤 细胞增殖 凋亡
Keywords:
endoplasmic reticulum stress high fatty acid palmitic acid myocardial injury cell proliferation apoptosis
分类号:
R-332;R322.11;R329.24;R587.2;R589.2
DOI:
10.3969/j.issn.1001-1978.2017.07.016
文献标志码:
A
摘要:
目的 探讨内质网应激信号通路在高脂诱导的心肌细胞损伤中的作用。方法 棕榈酸(0.1~0.4 mmol·L-1)刺激心肌细胞(0~48 h),CCK-8法评估细胞生长状态,免疫印迹法评估细胞内内质网应激信号通路相关蛋白表达水平及细胞凋亡蛋白表达水平。结果 棕榈酸(0.1~0.4 mmol·L-1)刺激H9C2心肌细胞24 h, 0.2、0.4 mmol·L-1组细胞增殖率均出现明显下降。棕榈酸(0.2 mmol·L-1)刺激H9C2心肌细胞时,24、48 h 组细胞增殖率均出现明显下降。棕榈酸(0.2 mmol·L-1)刺激24 h,GRP78、 CHOP、PERKphos、IRE1phos、ATF6等内质网应激相关蛋白及Bax蛋白表达均明显增高(P<0.05),而Bcl-2表达出现明显降低(P<0.05)。预处理内质网应激抑制剂普伐他汀(pravastatin,10 mol·L-1)的棕榈酸(0.2 mmol·L-1)组与不加pravastatin的棕榈酸(0.2 mmol·L-1)组相比,Bcl-2及Bax的表达均恢复至正常水平。结论 内质网应激信号通路对高脂引起的心肌损伤的发病及治疗均起到重要作用。
Abstract:
Aim To explore the role of endoplasmic reticulum stress(EPR)in high fatty acid induced injury in cardiomyocytes. Methods Cardiomyocytes were exposed to different concentrations of palmitic acid(0, 0.1, 0.2, 0.4 mmol·L-1)for 24 h and different time points of high palmitic acid(0.2 mmol·L-1)(12, 24, 48 h). Cell viability was measured by CCK8, and the protein expressions of EPR such as GRP78, CHOP, PERKphos, IRE1phos, ATF6 and apoptosis related proteins such as Bcl-2 and Bax were determined by Western blot. Results When the cells were stimulated with palmitic acid(0.1~0.4 mmol·L-1)for 24 h, the cell proliferation rates of 0.2 and 0.4 mmol·L-1 groups were significantly decreased. Cardiomyocytes exposured to high palmitic acid(0.2 mmol·L-1)for 24 h showed an increase in the expression of EPR related proteins(GRP78, CHOP, PERKphos, IRE1phos and ATF6)and Bax(P<0.05), while Bcl-2 expression was significantly reduced. Pretreatmented with EPR inhibitor pravastatin( 10 mol·L-1 )significantly increased high palmitic acid induced Bcl-2 expression(P<0.05)and significantly decreased high palmitic acid induced Bax expression(P<0.05). Conclusion Activated EPR might play an important role in treatment of high fatty acid induced myocardial injury.

参考文献/References:

[1] Caroline S F, Sherita H G, Cheryl A. Update on prevention of cardiovascular disease in adults with type 2 diabetes mellitus in light of recent evidence: a scientific statement from the american heart association and the american aiabetes association[J]. Diabetes Care, 2015, 38(9): 1777-803.
[2] Yeun S C, Jung S L, Woocheol K. Pulmonary langerhans cell histiocytosis in an adult male presenting with central diabetes insipidus and diabetes mellitus: a case report[J]. Tuberc Respir Dis(Seoul), 2015, 78(4): 463-8.
[3] 吴佳蕾,许惠琴,沈存思. 山茱萸配伍组分对糖尿病大鼠心血管病变的保护作用[J]. 中国药理学通报, 2013, 29(3): 382-6.
[3] Wu J L, Xu H Q, Shen C S. Protective effects of the Cornus of ficinalis compatibility of components on cardiovascular lesion in diabetic rats[J]. Chin Pharmacol Bull, 2013, 29(3): 382-6.
[4] 李 哲, 王瑞英, 张志成. 血清游离脂肪酸代谢及成分变化与2型糖尿病患者大血管并发症的关系[J]. 转化医学杂志, 2016, 5(4): 219-23.
[4] Li Z, Wang R Y, Zhang Z C. The relationship between serum free fatty acid metabolism and changes of components and macrovascular complications in patients with type 2 diabetes mellitus [J]. J Transl Med, 2016, 5(4): 219-23.
[5] 陈名道. 胰岛β细胞的“糖毒性”、“脂毒性”与“糖脂毒性”[J]. 中华内分泌代谢杂志, 2009, 25(1): 5-8.
[5] Chen M D. The "carbohydrate toxicity", "lipid toxicity" and "glycolipid toxicity" of islet β cells[J]. Chin J Endocr Metab, 2009, 25(1): 5-8.
[6] 莫雷同, 吴 铿. 脂毒性在糖尿病心肌病发病机制中的作用研究进展[J]. 现代医药卫生, 2015, 31(10): 1489-91.
[6] Mo L T, Wu J. Advances in studies on the role of lipid toxicity in the pathogenesis of diabetic cardiomyopathy[J]. Mod Med Health, 2015, 31(10): 1489-91.
[7] 吴 斌, 张 玫, 吕瑞雪. 表氧化二十碳三烯酸对游离脂肪酸诱导胰岛β细胞凋亡的抑制作用[J]. 世界华人消化杂志, 2012, 20(13): 1088-93.
[7] Wu B, Zhang M, Lyu R X. Inhibitory effect of epoxidized eicosatrienoic acid on apoptosis induced by free fatty acid in[J]. World Chin J Digestol, 2012, 20(13): 1088-93.
[8] 吉慧珍, 杨 静, 邢小平. 内质网应激、miR-375在高糖高脂介导胰岛β细胞凋亡中的作用[J]. 中国卫生检验杂志, 2016, 26(14): 2065-7.
[8] Gu H Z, Yang J, Xing X P. Endoplasmic reticulum stress, miR-375 in high glucose and high fat mediated pancreatic β-cell apoptosis in the role[J]. Chin J Health Lab Technol, 2016, 26(14): 2065-7.
[9] Zoltán V V, Zoltán G, Lucas L. Interplay of oxidative, nitrosative/nitrative stress, inflammation, cell death and autophagy in diabetic cardiomyopathy[J]. Biochim Biophys Acta, 2015, 1852(2): 232-42.
[10] Guanghong J, Vincent G D, James R S. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy[J]. Nat Rev Endocrinol, 2016, 12(3): 144-53.
[11] Yan X Q, Chen J, Zhang C. FGF21 deletion exacerbates diabetic cardiomyopathy by aggravating cardiac lipid accumulation[J]. J Cell Mol Med, 2015, 19(7): 1557-68.
[12] Raffay S K, Aalap C, Konstantinos D. Fish oil selectively improves heart function in a mouse model of lipid-induced cardiomyopathy[J]. J Cardiovasc Pharmacol, 2013, 61(4): 345-54.
[13] Xu J C, Zhou Q, Xu W. Endoplasmic reticulum stress and diabetic cardiomyopathy[J]. Exp Diabetes Res, 2012, 2012(1687-5214): 827971.
[14] 李赫宁, 李兰芳, 陈临溪. 内质网自噬—疾病防治的新靶标[J]. 中国药理学通报, 2015, 31(3): 302-8.
[14] Li H N, Li L F, Chen L X. Reticulophagy-a new target for diseases prevention and treatment[J]. Chin Pharmacol Bull, 2015, 31(3): 302-8.
[15] Liu M Q, Chen Z, Chen L X. Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases[J]. Acta Pharmacol Sin, 2016, 37(4): 425-43.

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备注/Memo

备注/Memo:
基金项目: 湖北省教育厅科学研究计划资助项目(No B201696); 湖北科技学院糖尿病专项基金资助项目(No 2016-18XZ09); 湖北科技学院博士启动基金资助项目(No BK1432)
作者简介: 陈 丹(1990-),女,硕士生,研究方向:心血管药理学,E-mail:840627354@qq.com;
李 晶(1979-),女,博士,副教授,研究方向:糖尿病心脑血管病变,通讯作者,E-mail:lijing790629@:163.com
更新日期/Last Update: 2017-07-15