大蒜辣素对db/db糖尿病小鼠心肌细胞凋亡及Pink1/Parkin信号通路的影响

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (6): 601-605.

• 基础研究 • 下一篇

大蒜辣素对db/db糖尿病小鼠心肌细胞凋亡及Pink1/Parkin信号通路的影响

荆哲¹, 刘峰舟², 郭文韵¹, 焦丕齐¹, 陈永清¹

¹甘肃省兰州市兰州军区兰州总医院心血管内科，兰州 730050，甘肃； ²甘肃省临洮县空军94195部队卫生队，定西 730500，甘肃

收稿日期:2016-11-09 修回日期:2017-03-13 出版日期:2017-06-26 发布日期:2017-06-26
通讯作者: 陈永清，男，博士研究生，主任医师，研究方向：缺血性心肌病及糖尿病心肌病相关机制。 E-mail：chenyq323@163.com
作者简介:荆哲，男，硕士研究生，主治医师，研究方向：糖尿病心肌病的发生及发展相关机制。 E-mail：35082774@qq.com
基金资助:
国家自然科学基金青年科学基金项目（81400197）

Effect of allicin on apoptosis and Pink1/Parkin signal path of cardiomyocyte in db/db mice

JING Zhe¹, LIU Fengzhou ², GUO Wenyun¹, JIAO Piqi ¹, CHEN Yongqing¹

¹ Department of Cardiology, Lanzhou General Hospital of Lanzhou Military Region, Lanzhou 730050, Gansu, China; ²Medical Unit,Liberation army NO.94195, Dingxi 730500, Gansu, China

Received:2016-11-09 Revised:2017-03-13 Online:2017-06-26 Published:2017-06-26

摘要/Abstract

摘要：

目的: 观察大蒜辣素对db/db糖尿病小鼠心肌细胞凋亡及Pink1/Parkin信号通路的影响。方法: 在db/db糖尿病小鼠模型的基础上，随机分为糖尿病模型组及大蒜辣素组，同时设正常对照组。连续干预21 d后处死剪取左心室组织。采用TUNEL染色法分析各组心肌细胞的凋亡水平；采用Western blot及qRT-PCR检测Pink1、Parkin及Mfn1的表达情况。结果: 糖尿病模型组心肌细胞凋亡明显增多，大蒜辣素组心肌细胞凋亡改善明显；糖尿病模型组Parkin表达明显降低，大蒜辣素组表达明显增多，而Pink1的表达水平各处理组无明显差异。糖尿病模型组心肌细胞Mfn1表达明显增高；大蒜辣素组与糖尿病模型组相比，Mfn1表达明显降低。结论: 大蒜辣素可有效抑制糖尿病心肌细胞凋亡，并通过激活Pink1/Parkin信号通路以保护心肌。

关键词: 大蒜辣素, 心肌细胞, 凋亡, db/db小鼠, Parkin

Abstract:

AIM: To observe the effect of allicin on apoptosis and Pink1/Parkin signal path of cardiomyocyte in db/db mice. METHODS: Diabetes models were randomly divided into diabetes model group and allicin group. After 21 days of injection, all mice were sacrificed and samples were gathered. Cell apoptosis was analyzed using TUNEL. The mRNA and protein expression level of Pink1, Parkin and Mfn1 were detected by qRT-PCR and Western blot. RESULTS: Severe cardiomyocyte apoptosis, lower expression of Parkin, and higher expression of Mfn1 were observed in diabetes model group, while in allicin group, such changes were improved. CONCLUSION:A llicin can effectively restrain cardiomyocyte apoptosis and protect cardiomyocyte by activating Pink1/Parkin signal path.

Key words: allicin, cardiomyocyte, apoptosis, db/db mice, Parkin

中图分类号:

R965.2

荆哲, 刘峰舟, 郭文韵, 焦丕齐, 陈永清. 大蒜辣素对db/db糖尿病小鼠心肌细胞凋亡及Pink1/Parkin信号通路的影响[J]. 中国临床药理学与治疗学, 2017, 22(6): 601-605.

JING Zhe, LIU Fengzhou, GUO Wenyun, JIAO Piqi, CHEN Yongqing. Effect of allicin on apoptosis and Pink1/Parkin signal path of cardiomyocyte in db/db mice[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(6): 601-605.

参考文献

［1］Di Pino A, Urbano F, Piro S, et al.Update on pre-diabetes: Focus on diagnostic criteria and cardiovascular risk［J］.World J Diabetes, 2016, 7(18):423-432.
［2］Vancampfort D, Mugisha J, Hallgren M, et al.The prevalence of diabetes mellitus type 2 in people with alcohol use disorders: a systematic review and large scale meta-analysis［J］.Psychiatry Res, 2016, 246:394-400.
［3］Yin J, Kong AP, Chan JC. Prevention and care programs addressing the growing prevalence of diabetes in China ［J］.Curr Diab Rep, 2016, 16(12):130.
［4］Zhao YZ, Zhang M, Tian XQ, et al. Using basic fibroblast growth factor nanoliposome combined with ultrasound-introduced technology to early intervene the diabetic cardiomyopathy ［J］. Int J Nanomedicine, 2016,18(11):675-686.
［5］Mizamtsidi M, Paschou SA, Grapsa J, et al. Diabetic cardiomyopathy: a clinical entity or a cluster of molecular heart changes［J］? Eur J Clin Invest, 2016, 46(11):947-953.
［6］Ong SB, Hausenloy DJ. Mitochondrial morphology and cardiovascular disease［J］. Cardiovasc Res, 2010, 88(1):16-29.
［7］An D, Rodrigues B. Role of changes in cardiac metabolism in development of diabetic cardiomyopathy［J］. Am J Physiol Heart Circ Physiol, 2006, 291(4):H1489-1506.
［8］Poole AC, Thomas RE, Andrews LA, et al. The PINK1/Parkin pathway regulates mitochondrial morphology［J］. Proc Natl Acad Sci U S A, 2008,105 (5) 1638-1643.
［9］Deng H, Dodson MW, Huang H, et al. The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila［J］. Proc Natl Acad Sci U S A, 2008, 105 (38)：14503-14508.
［10］Yu W, Gao B, Li N, et al.Sirt3 deficiency exacerbates diabetic cardiac dysfunction: Role of Foxo3A-Parkin-mediated mitophagy ［J］.Biochim Biophys Acta, 2017，1863（8）：1973-1983.
［11］Sheppard JG, Long TE.Allicin-inspired thiolated fluoroquinolones as antibacterials against ESKAPE pathogens［J］.Bioorg Med Chem Lett, 2016, 26(22): 5545-5549.
［12］Hayat S, Cheng Z, Ahmad H, et al.Garlic, from remedy to stimulant: evaluation of antifungal potential reveals diversity in phytoalexin allicin content among garlic cultivars; allicin containing aqueous garlic extracts trigger antioxidants in cucumber ［J］.Front Plant Sci, 2016, 7:1235.
［13］Panyod S, Wu WK, Ho CT, et al. Diet supplementation with allicin protects against alcoholic fatty liver disease in mice by improving anti-inflammation and antioxidative functions［J］.J Agric Food Chem, 2016, 64(38):7104-7113.
［14］Ma LN, Li LD, Li SC, et al. Allicin improves the cardiac function by protecting against apoptosis in rat model of myocardial infarction［J］.Chin J Integr Med, 2016 Jul 13. ［Epub ahead of print］
［15］Huang H, Jiang Y, Mao G, et al. Protective effects of allicin on streptozotocin-induced diabetic nephropathy in rats［J］.J Sci Food Agric,2016, 97(4):1359-1366.
［16］Zou X, Liang J, Sun J, et al.Allicin sensitizes hepatocellular cancer cells to anti-tumor activity of 5-fluorouracil through ROS-mediated mitochondrial pathway ［J］.J Pharmacol Sci, 2016, 131(4):233-240.
［17］李少春,马丽娜,陈坚,等.大蒜辣素对大鼠心肌梗死后纤维化的影响及与TGFβ/Smads信号通路的关系［J］.中国中药杂志, 2016, 41:2517-2521.
［18］史云秋,王旭.从五脏论治2型糖尿病［J］.长春中医药大学学报,2015,31(1):68-70.
［19］Ma LN, Li LD, Li SC, et al. Allicin improves the cardiac function by protecting against apoptosis in rat model of myocardial infarction［J］.Chin J Integr Med, 2016 Jul 13. ［Epub ahead of print］.
［20］Chen X, Pang S, Lin J, et al. Allicin prevents oxidized low-density lipoprotein-induced endothelial cell injury by inhibiting apoptosis and oxidative stress pathway ［J］.BMC Complement Altern Med, 2016, 16:133.
［21］Boudina S, Abel ED. Mitochondrial uncoupling: a key contributor to reduced cardiac efficiency in Diabetes［J］. Physiology (Bethesda), 2006, 21:250-258.
［22］De Rosa A, Pellegrino T, Pappatà S, et al.Myocardial 123I-metaiodobenzylguanidine scintigraphy in patients with homozygous and heterozygous parkin mutations［J］.J Nucl Cardiol,2015, 24(1):103-107.
［23］Santel A, Fuller MT. Control of mitochondrial morphology by a human mitofusin［J］. J Cell Sci, 2001, 114(Pt 5):867-874.
［24］Tanaka A, Cleland MM, Xu S, et al. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin［J］. J Cell Biol, 2010,191(7) 1367-1380.
［25］Bhandari P, Song M, Chen Y, et al. Mitochondrial contagion induced by Parkin deficiency in Drosophila hearts and its containment by suppressing mitofusin［J］. Circ Res,2014,114 (2):257-265.

[1]	范杰, 金永明, 江孝龙, 蒋国华. lncRNA HOTAIR调控miR-206影响类风湿关节炎滑膜细胞增殖和凋亡的分子机制研究[J]. 中国临床药理学与治疗学, 2023, 28(7): 736-742.
[2]	杨晓佳, 江萌, 吴敏, 张伊黎, 吕兰, 吴嫄芬, 王鑫昱, 刘立权. 藏红花素介导DKK3调控GSK-3β/β-catenin通路对阿尔兹海默症大鼠的认知改善作用[J]. 中国临床药理学与治疗学, 2023, 28(5): 489-497.
[3]	侯小煜, 冷玉芳, 曹雪芬, 吕兴娇, 韩晓霞, Janvier NIBARUTA, 刘永强. 五味子乙素减轻小鼠肠缺血再灌注损伤的网络药理学分析及实验验证[J]. 中国临床药理学与治疗学, 2023, 28(2): 147-154.
[4]	王剑, 孙永东, 周兴玮, 刘雷, 陈龙, 童兴科, 朱佳丽. 黄芩素经由miR-125b-5p/IRF4轴进而促进喉癌细胞死亡并抑制其侵袭的机制研究[J]. 中国临床药理学与治疗学, 2023, 28(11): 1209-1218.
[5]	朱瑞芳, 郭东凯, 智慧, 江翊国, 张悦翎, 钱晓萍, 季士亮. ROS-NF-κB-p38MAPK通路探索榄香烯联合硼替佐米抗多发性骨髓瘤的机制研究[J]. 中国临床药理学与治疗学, 2023, 28(11): 1219-1226.
[6]	周欢, 徐铭, 李波, 刘春英, 王淳. PI3K/Akt/FOXO3a信号通路介导的保护性自噬参与肺腺癌获得性顺铂耐药表型重塑[J]. 中国临床药理学与治疗学, 2022, 27(9): 961-970.
[7]	华海燕, 严杰, 秦宇芬. 五味子乙素通过抑制心肌细胞凋亡减轻大鼠心肌缺血再灌注损伤的实验研究[J]. 中国临床药理学与治疗学, 2022, 27(8): 848-856.
[8]	李雪恒, 李龙. 褪黑素与特发性肺纤维化关系的研究进展[J]. 中国临床药理学与治疗学, 2022, 27(6): 715-720.
[9]	杨柳, 罗爱林, 李世勇. 全麻药物损伤发育期大脑的研究进展[J]. 中国临床药理学与治疗学, 2022, 27(12): 1381-1390.
[10]	谭峰浪, 任宏丽, 王宏飞. 黄柏提取物对Aβ_1-42诱导的海马神经细胞的影响[J]. 中国临床药理学与治疗学, 2022, 27(11): 1213-1220.
[11]	潘蓉蓉, 支英豪, 金永喜, 周夏慧. 茶黄素调节CaMKK2/AMPK信号通路对脑出血大鼠神经元凋亡和血脑屏障的影响[J]. 中国临床药理学与治疗学, 2022, 27(11): 1240-1246.
[12]	李莹, 姚伟, 王萌, 余志宏, 龚园其, 蓝海兵, 齐协飞. 鸢尾素通过NF-κB和JNK信号通路减轻屋尘螨诱导的气道上皮细胞炎症及凋亡的实验研究[J]. 中国临床药理学与治疗学, 2022, 27(10): 1106-1112.
[13]	刘晓萍, 赖香茂, 欧阳资章, 江晟, 张莹. 川陈皮素抑制高糖诱导的乳鼠心肌细胞肥大[J]. 中国临床药理学与治疗学, 2021, 26(7): 753-759.
[14]	刘云帆, 杜月梅, 刘晓艺, 高丽萍. 枸杞多糖对顺铂诱导小鼠睾丸支持细胞凋亡的影响[J]. 中国临床药理学与治疗学, 2021, 26(6): 624-630.
[15]	魏松长, 杨红琪, 张宏娟, 施晓丽, 任凯文. RON蛋白与CXC趋化因子受体4蛋白的表达与去势抵抗型前列腺癌患者阿比特龙耐药的相关性[J]. 中国临床药理学与治疗学, 2021, 26(4): 414-422.

大蒜辣素对db/db糖尿病小鼠心肌细胞凋亡及Pink1/Parkin信号通路的影响

Effect of allicin on apoptosis and Pink1/Parkin signal path of cardiomyocyte in db/db mice

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价