山楂酸减少高糖介导的心肌细胞损伤和凋亡及其机制(PDF)
《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]
- 期数:
- 2017年第3期
- 页码:
- 276-280
- 栏目:
- 基础研究
- 出版日期:
- 2017-01-25
文章信息/Info
- Title:
- Effect and mechanism of maslinic acid on attenuating high glucose-induced myocardial cell injury and apoptosis
- Author(s):
- ZOU Yong; ZHAO Xiao-kui; SUN Yu-mei; WANG Jian-gang
- Department of Cardiology, Hospital of Changqing Oilfield, Xi’an 710201, Shaanxi, China
- Keywords:
- diabetic cardiomyopathy; maslinic acid; myocardial cell; apoptosis
- 分类号:
- R284.1
- DOI:
- -
- 文献标识码:
- A
- 摘要:
- 目的 探讨山楂酸处理对高糖介导大鼠心肌细胞H9c2损伤和凋亡分子机制影响。方法 以高糖诱导大鼠心肌细胞 H9c2为模型，采用乳酸脱氢酶(LDH)法检测细胞损伤情况，TUNEL化学染色检测细胞凋亡率，Western blot检测AMPK的磷酸化水平以及Bcl-2、Bax的表达水平，免疫荧光检测细胞活性氧（ROS）的生成。结果 ①与对照组相比，高糖组细胞LDH活性和细胞凋亡比率显著增高（P<0.05），山楂酸处理却能抑制高糖诱导的H9c2细胞LDH的积累，降低细胞凋亡（P<0.05）。②Western blot检测显示，与对照组相比，高糖组p-AMPK、Bcl-2下调（P<0.05），Bax上调（P<0.05）；与高糖组相比，山楂酸处理组p-AMPK、Bcl-2上调（P<0.05），Bax下调（P<0.05），给予AMPK阻断剂 Compound C后可以抑制山楂酸诱发的这些效应（P<0.05）。③ROS检测显示，山楂酸能够抑制高糖刺激的ROS的产生（P<0.05），而AMPK拮抗剂compound c却能够拮抗山楂酸对ROS的抑制（P<0.05）。结论 山楂酸能通过激活AMPK信号通路，从而增强BCl-2表达、抑制Bax和ROS生成，拮抗高糖诱导的大鼠心肌细胞H9c2凋亡，对心肌细胞起保护作用。
- Abstract:
- AIM To investigate the role of maslinic acid in high glucose-induced rat myocardial cell H9c2 apoptosis and possible mechanisms of action. METHODS High glucose-induced rat myocardial cell H9c2 model was constructed. Lactate dehydrogenase (LDH) release was used to test the degree of injury. TUNEL staining was used to detect the apoptosis. Western blot was used to detect the expression of AMPK, BCl-2 and Bax in H9c2 cells, and immunofluorescence assay was used to detect the reactive oxygen species (ROS) generation of myocardial mitochondria. RESULTS Compared with those in the control group, high glucose-treated cells exhibited a significant increase of LDH activity and apoptosis, whereas maslinic acid prevented the increase in high glucose-induced accumulation of LDH and decreased the degree of apoptosis. Western blot showed that the expression of p-AMPK and Bcl-2 decreased, but the expression of Bax increased in the high glucose group compared with those in the control group. Treatment with maslinic acid up-regulated p-AMPK and Bcl-2 and down-regulated Bax. However, Compound C, a special AMPK antagonist, reversed these effects induced by maslinic acid. Furthermore, ROS analysis revealed that maslinic acid inhibited high glucose-stimulated production of ROS, whereas pretreatment with AMPK antagonist compound C reversed maslinic acid and restrained ROS generation. CONCLUSION Maslinic acid exerts a protective effect on myocardium by activating AMPK, enhancing Bcl-2 expression and inhibiting Bax and ROS generation and high glucose-induced apoptosis.
参考文献/References
[1]Stratmann B,Worms J,Tschoepe D.Diabetic cardiomyopathy/heart failure:news regarding etiology,diagnosis,therapy[J].Dtsch Med Wochenschr,2014,139(40):2006-2009.
[2]Bai T,Wang F,Mellen N,et al.Diabetic Cardiomyopathy:Role of the E3 Ubiquitin Ligase[J].Am J Physiol Endocrinol Metab,2016,310(7):E473-E483.
[3]Voulgari C,Papadogiannis D,Tentolouris N.Diabetic cardiomyopathy:from the pathophysiology of the cardiac myocytes to current diagnosis and management strategies[J].Vasc Health Risk Manag,2010,6:883-903.
[4]Roe ND,Thomas DP,Ren J.Inhibition of NADPH oxidase alleviates experimental diabetes-induced myocardial contractile dysfunction[J].Diabetes Obes Metab,2011,13(5):465-473.
[5]Gao L,Mann GE.Vascular NAD(P)H oxidase activation in diabetes:a double-edged sword in redox signalling[J].Cardiovasc Res,2009,82(1):9-20.
[6]Varga ZV,Giricz Z,Liaudet L,et al.Interplay of oxidative, nitrosative/nitrative stress, inflammation,cell death and autophagy in diabetic cardiomyopathy[J].Biochim Biophys Acta,2015,1852(2):232-242.
[7]Cave AC,Brewer AC,Narayanapanicker A,et al.NADPH oxidases in cardiovascular health and disease[J].Antioxid Redox Signal,2006,8(5-6):691-728.
[8]Dobrin JS,Lebeche D.Diabetic cardiomyopathy:signaling defects and therapeutic approaches[J].Expert Rev Cardiovasc Ther,2010,8(3):373-391.
[9]Saran V,Sharma V,Wambolt R,et al.Combined metoprolol and ascorbic acid treatment prevents intrinsic damage to the heart during diabetic cardiomyopathy[J].Can J Physiol Pharmacol,2014,92(10):827-837.
[10]Macdonald K,Bailey J,Macrory C,et al.A newly synthesised molybdenum/ascorbic acid complex alleviates some effects of cardiomyopathy in streptozocin-induced diabetic rats[J]. Drugs R D,2006,7(1):33-42.
[11]Mkhwanazi BN,Serumula MR,Myburg RB,et al.Antioxidant effects of maslinic acid in livers,hearts and kidneys of streptozotocin-induced diabetic rats:effects on kidney function[J].Ren Fail,2014,36(3):419-431.
[12]Mokhtari K,Rufino-Palomares EE,Perez-Jimenez A,et al.Maslinic Acid,a Triterpene from Olive,Affects the Antioxidant and Mitochondrial Status of B16F10 Melanoma Cells Grown under Stressful Conditions[J].Evid Based Complement Alternat Med,2015,2015:272457.
[13]Montilla MP,Agil A,Navarro MC,et al.Antioxidant activity of maslinic acid, a triterpene derivative obtained from Olea europaea[J].Planta Med,2003,69(5):472-474.
[14]Xu HX,Zeng FQ,Wan M,et al.Anti-HIV triterpene acids from Geum japonicum[J].J Nat Prod,1996,59(7):643-645.
[15]Neubauer S.The failing heart-an engine out of fuel[J].N Engl J Med,2007,356(11):1140-1151.
[16]Qin X,Qiu C,Zhao L.Maslinic acid protects vascular smooth muscle cells from oxidative stress through Akt/Nrf2/HO-1 pathway[J].Mol Cell Biochem,2014,390(1-2):61-67.
备注/Memo
- 备注/Memo:
- 收稿日期：2016-06-01.通讯作者：王建刚，主任医师，主要从事心血管生理研究 Email:1294427507@qq.com 作者简介：邹勇，主治医师，学士 Email:cqzgzxnk@163.com
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