麝香保心丸通过抑制p38 MAPK和NF-κB信号传导通路表达对抗高糖诱导的心肌细胞损伤

doi:10.13418/j.issn.1001-165x.2016.05.009

中国临床解剖学杂志 ›› 2016, Vol. 34 ›› Issue (5): 517-522.doi: 10.13418/j.issn.1001-165x.2016.05.009

麝香保心丸通过抑制p38 MAPK和NF-κB信号传导通路表达对抗高糖诱导的心肌细胞损伤

杨翼鹰¹，陈伟燕²，　孙秀亭¹，　王翔³，　李政勋¹，　梁美玲⁴，　石卉¹，　杨至圣¹，　曾武涛¹

1.中山大学附属第一医院心内科，广州 510080；　2.广州医科大学附属第二医院ICU，广州 510260；
3.莱芜市人民医院心内科，山东莱芜 271100； 4.深圳市孙逸仙心血管医院心内科，广东深圳 518020

收稿日期:2015-10-26 出版日期:2016-09-25 发布日期:2016-10-14
通讯作者: 曾武涛，教授，硕士生导师，E-mail：zengwutao_sysumed@163.com
作者简介:杨翼鹰（1990-），男，在读硕士，研究方向：心血管疾病的损伤与保护机制，E-mail：yangyiy_sysumed@163.com
基金资助:
中国中西医结合学会-和黄科研基金（2014002）

Shexiang baoxin pill protects cardiomyocytes against high glucose-induced injury by inhibiting the p38 MAPK and NF-κB pathway

YANG Yi-ying¹, CHEN Wei-yan², SUN Xiu-ting¹, WANG Xiang³, LI Zheng-xun¹, LIANG Mei-ling⁴, SHI Hui¹, YANG Zhi-sheng¹, ZENG Wu-tao¹

1. Department of Cardiology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080，China; 2. Intensive Care Unit, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China; 3. Department of Cardiology, Laiwu City People’s Hospital, Laiwu, Shandong 27110, China; 4. Department of Cardiology, Sun Yat-sen Cardiovascular Hospital, Shenzhen, Guangdong 518020, China

Received:2015-10-26 Online:2016-09-25 Published:2016-10-14

摘要/Abstract

摘要：

目的　探讨麝香保心丸（SBP）是否通过抑制p38丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）和核因子kappa B（nuclear factor kappa B，NF-κB）通路保护H9c2心肌细胞对抗高浓度葡萄糖（高糖，HG）引起的损伤。方法　应用35 mmol /L的HG处理H9c2心肌细胞24 h，建立HG诱导的心肌细胞损伤模型；细胞计数试剂盒8测定细胞存活率；Hoechst 33258核染色荧光显微镜照相法测定细胞凋亡；双氯荧光素（2’，7’-dichlorfluorescein-diacetate，DCFH-DA）染色/荧光显微镜照相法测定胞内活性氧（ROS）水平；罗丹明123（Rh123）染色法测定线粒体膜电位（MMP）；Western blot法测定p38 MAPK和NF-κB p65蛋白表达水平。结果　HG处理H9c2心肌细胞24 h能引起细胞明显的损伤，使细胞存活率降低，凋亡细胞数量和细胞内ROS生成增多，MMP丢失；HG能增加p38 MAPK和NF-κB p65磷酸化水平；SBP预处理能明显抑制HG上调p38 MAPK和NF-κB p65磷酸化水平这一作用；SBP、p38 MAPK通路抑制剂SB203580和NF-κB通路抑制剂PDTC均能阻断HG 对心肌细胞的上述损伤作用，包括细胞毒性、凋亡、ROS生成增多及MMP丢失等。结论　麝香保心丸（SBP）可通过抑制p38 MAPK和NF-κB信号传导通路保护H9c2心肌细胞对抗高糖（HG）引起的损伤。

关键词: 麝香保心丸, 高血糖, p38 MAPK, NF-&kappa, B, 心肌细胞

Abstract:

Objective　To explore whether Shexiang Baoxin Pill（SXBXP/SBP）protects H9c2 cardiac cells against high glucose（HG）-induced injury by inhibition of p38 MAPK and NF-κB pathway．Methods　H9c2 cardiac cells were treated with 35 mmol/L glucose（HG）for 24h to establish a model of HG-induced injury；Cell counter kit-8（CCK-8）was used to measure cell viability；Apoptotic cells were tested by Hoechst 33258 nuclear staining followed by fluorescence imaging；Intracellular levels of reactive oxygen species（ROS）were detected by 2’，7’-dichlorfluorescein-diacetate（DCFH-DA）staining，followed by fluorescence imaging; Mitochondrial membrane potential （MMP）was measured by a fluorescent dye，rhodamine 123（Rh123），followed by fluorescence imaging；The expression levels of p38 MAPK and NF-κB p65 protein were detected by Western blot assay.　Result　Treatment of H9c2 cardiac cells with HG for 24h signally induced injuries，proved by a decrease in cell viability，an increase in amount of apoptotic cells and intracellular ROS production，as well as a loss of MMP；HG strengthened the expression of phosphorylated（p）-p38 MAPK and p-NF-κB p65; Pretreatment with SBP notably inhibited the up-regulation of expression of p-p38 MAPK and p-NF-κB p65 induced by HG; Pretreatment with SBP or SB203580，an inhibitor of p38 pathway or PDTC, an inhibitor of NF-κB pathway，attenuated the above HG-induced injuries，including cytotoxicity，apoptosis，increase in ROS production and a loss of MMP，in H9c2 cardiac cells.　Conclusion　SXBXP（SBP） may protect H9c2 cardiac cells against the HG-induced injuries by inhibiting the p38 MAPK and NF-κB pathway．

Key words: Shexiang Baoxin Pill, High glucose, p38 MAPK, NF-κB, Cardiomyocyte

杨翼鹰,陈伟燕,孙秀亭,王翔,李政勋,梁美玲,石卉,杨至圣,曾武涛. 麝香保心丸通过抑制p38 MAPK和NF-κB信号传导通路表达对抗高糖诱导的心肌细胞损伤[J]. 中国临床解剖学杂志, 2016, 34(5): 517-522.

YANG Yi-ying, CHEN Wei-yan, SUN Xiu-ting, WANG Xiang, LI Zheng-xun, LIANG Mei-ling, SHI Hui, YANG Zhi-sheng, ZENG Wu-tao. Shexiang baoxin pill protects cardiomyocytes against high glucose-induced injury by inhibiting the p38 MAPK and NF-κB pathway[J]. Chinese Journal Of Clinical Anatomy, 2016, 34(5): 517-522.

参考文献

[1] 周雯雯, 李田昌. 糖尿病性心肌病研究进展 [J]. 心血管病学进展, 2009, (4): 615-618.
[2] Zhang X, Lai D, Bao S, et al. Triamcinolone acetonide inhibits p38MAPK activation and neuronal apoptosis in early diabetic retinopathy [J]. Curr Mol Med, 2013, 13(6): 946-958.
[3] Cowan C, Muraleedharan CK, O'Donnell JJ 3rd, et al. MicroRNA-146 inhibits thrombin-induced NF-kappaB activation and subsequent inflammatory responses in human retinal endothelial cells [J]. Invest Ophthalmol Vis Sci, 2014, 55(8): 4944-4951.
[4] Lu HJ, Tzeng TF, Liou SS, et al. Polysaccharides from Liriopes Radix ameliorate streptozotocin-induced type I diabetic nephropathy via regulating NF-kappaB and p38 MAPK signaling pathways [J]. BMC Complement Altern Med, 2014, 13(14):156-156.
[5] Soetikno V, Sari FR, Sukumaran V, et al. Curcumin prevents diabetic cardiomyopathy in streptozotocin-induced diabetic rats: possible involvement of PKC-MAPK signaling pathway [J]. Eur J Pharm Sci, 2012, 47(3): 604-614.
[6] Chen J, Mo H, Guo R, et al. Inhibition of the leptin-induced activation of the p38 MAPK pathway contributes to the protective effects of naringin against high glucose-induced injury in H9c2 cardiac cells [J]. Int J Mol Med, 2014, 33(3): 605-612.
[7] Nizamutdinova IT, Guleria RS, Singh AB, et al. Retinoic acid protects cardiomyocytes from high glucose-induced apoptosis through inhibition of NF-kappaB signaling pathway [J]. J Cell Physiol, 2013, 228(2): 380-392.
[8] Chen J, Guo R, Yan H, et al. Naringin inhibits ROS-activated MAPK pathway in high glucose-induced injuries in H9c2 cardiac cells [J]. Basic Clin Pharmacol Toxicol, 2014, 114(4): 293-304.
[9] Kuo WW, Wang WJ, Tsai CY, et al. Diallyl trisufide (DATS) suppresses high glucose-induced cardiomyocyte apoptosis by inhibiting JNK/NFkappaB signaling via attenuating ROS generation [J]. Int J Cardiol, 2013, 168(1): 270-280.
[10]戴瑞鸿. 麝香保心丸的作用机制研究进展与临床评价 [J]. 中国医院用药评价与分析, 2006, (1): 15-17.
[11]王军锋, 韩灵敏, 程芳, et al. 麝香保心丸联合西药治疗糖尿病性心肌病49例 [J]. 陕西中医, 2014, (9): 1175-1176.
[12]Taye A, Abouzied MM, Mohafez OM. Tempol ameliorates cardiac fibrosis in streptozotocin-induced diabetic rats: role of oxidative stress in diabetic cardiomyopathy [J]. Naunyn Schmiedebergs Arch Pharmacol, 2013, 386(12): 1071-1080.
[13]Xu W, Wu W, Chen J, et al. Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1/2 pathways [J]. Int J Mol Med, 2013, 32(4): 917-925.
[14]Cheng HB, Bo Y, Shen WX, et al. Longikaurin E induces apoptosis of pancreatic cancer cells via modulation of the p38 and PI3K/AKT pathways by ROS [J]. Naunyn Schmiedebergs Arch Pharmacol, 2015, 388(6): 623-634.
[15]Gu W, Song L, Li XM, et al. Mesenchymal stem cells alleviate airway inflammation and emphysema in COPD through down-regulation of cyclooxygenase-2 via p38 and ERK MAPK pathways [J]. Sci Rep, 2015, 4(5):8733-8733.
[16]Wang W, Tang L, Li Y, et al. Biochanin A protects against focal cerebral ischemia/reperfusion in rats via inhibition of p38-mediated inflammatory responses [J]. J Neurol Sci, 2015, 348(1-2): 121-125.

[17]Sellami H, Said-Sadier N, Znazen A, et al. Chlamydia trachomatis infection increases the expression of inflammatory tumorigenic cytokines and chemokines as well as components of the Toll-like receptor and NF-kappaB pathways in human prostate epithelial cells [J]. Mol Cell Probes, 2014, 28(4): 147-154.
[18]Qazi AK, Hussain A, Aga MA, et al. Cell specific apoptosis by RLX is mediated by NFkappaB in human colon carcinoma HCT-116 cells [J]. BMC Cell Biol, 2014, 10(15):36-36.
[19]Kumar M, Sahu SK, Kumar R, et al. MicroRNA let-7 modulates the immune response to Mycobacterium tuberculosis infection via control of A20, an inhibitor of the NF-kappaB pathway [J]. Cell Host Microbe, 2015, 17(3): 345-356.
[20]Wang DT, Huang RH, Cheng X, et al. Tanshinone IIA attenuates renal fibrosis and inflammation via altering expression of TGF-beta/Smad and NF-kappaB signaling pathway in 5/6 nephrectomized rats [J]. Int Immunopharmacol, 2015, 26(1): 4-12.
[21]Sero JE, Sailem HZ, Ardy RC, et al. Cell shape and the microenvironment regulate nuclear translocation of NF-kappaB in breast epithelial and tumor cells [J]. Mol Syst Biol, 2015, 11(3): 790-790.
[22]Guo R, Wu K, Chen J, et al. Exogenous hydrogen sulfide protects against doxorubicin-induced inflammation and cytotoxicity by inhibiting p38MAPK/NFkappaB pathway in H9c2 cardiac cells [J]. Cell Physiol Biochem, 2013, 32(6): 1668-1680.
[23]丁燕萍, 王翼华, 王前, 等. 麝香保心丸对糖尿病合并冠心病患者胰岛素抵抗及糖、脂代谢的影响 [J]. 中国医药指南, 2013, (9): 656-657.
[24]刘小燕, 王远征, 韩玉. 麝香保心丸对糖尿病大鼠心肌纤维化的影响 [J]. 中药药理与临床, 2012, (1):28-31.

麝香保心丸通过抑制p38 MAPK和NF-κB信号传导通路表达对抗高糖诱导的心肌细胞损伤

Shexiang baoxin pill protects cardiomyocytes against high glucose-induced injury by inhibiting the p38 MAPK and NF-κB pathway

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