[1]丁华胜,黄 燕,王凤媛.丹皮酚对心肌缺血再灌注损伤保护中Toll样受体4、心肌焦亡影响的作用机制[J].陕西中医,2021,(12):1659-1662.[doi:DOI:10.3969/j.issn.1000-7369.2020.12.001]
　DING Huasheng,HUANG Yan,WANG Fengyuan.Mechanism of influence on paeonol on TLR4 and myocardial pyrosis in protection of myocardial ischemia-reperfusion injury[J].,2021,(12):1659-1662.[doi:DOI:10.3969/j.issn.1000-7369.2020.12.001]
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丹皮酚对心肌缺血再灌注损伤保护中Toll样受体4、心肌焦亡影响的作用机制
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《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2021年12期
页码:
1659-1662
栏目:
基础研究
出版日期:
2021-12-05

文章信息/Info

Title:
Mechanism of influence on paeonol on TLR4 and myocardial pyrosis in protection of myocardial ischemia-reperfusion injury
作者:
丁华胜1; 黄 燕2; 王凤媛2
(1.武汉科技大学附属普仁医院急诊科,湖北 武汉 430081; 2.武汉大学心血管病研究所,湖北 武汉 430060)
Author(s):
DING Huasheng; HUANG Yan; WANG Fengyuan
(Department of Emergency, Puren Hospital,Wuhan University of Science and Technology,Wuhan 430081,China)
关键词:
丹皮酚;  心肌缺血再灌注损伤;  Toll样受体4;  NLRP3/Caspase-1信号通路;  细胞焦亡;  炎症因子
Keywords:
Paeonol;  Myocardial ischemia-reperfusion injury;  Toll like receptor 4;  NLRP3/Caspase-1 signing pathway;  Cell pyrolysis;  Inflammatory factor
分类号:
R 285
DOI:
DOI:10.3969/j.issn.1000-7369.2020.12.001
文献标志码:
A
摘要:
目的:探讨丹皮酚对大鼠心肌缺血再灌注损伤(MIRI)的作用机制及对Toll样受体4(TLR4)、细胞焦亡的影响。方法:将SD大鼠随机分为假手术组、缺血再灌注组、丹皮酚低剂量组(15 mg/kg)、丹皮酚高剂量组(30 mg/kg)。药物干预后,结扎左冠脉前降支0.5 h,再灌注4 h。再灌注结束后,采用生化分析法测定肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)水平; 2,3,5-氯化三苯基四氮唑蓝(TTC)染色法测定心肌梗死面积,免疫组化法测定TLR4蛋白水平; 免疫印迹(Western blot)法检测心肌组织NOD样受体家族Pyrin域3(NLRP3)、IL-1β、凋亡相关斑点蛋白(ASC)以及半胱天冬酶(Caspase)-1的表达。结果:与缺血再灌注组比较,丹皮酚低剂量组、丹皮酚高剂量组再灌注后LDH、CK-MB活性下降,心肌梗死面积减小,心肌组织TLR4、NLRP3、Caspase-1、ASC、IL-1β表达水平降低,差异有统计学意义(均P<0.05)。丹皮酚高剂量组的上述指标均低于丹皮酚低剂量组,差异有统计学意义(均P<0.05)。结论:丹皮酚预处理可抑制TLR4表达,下调NLRP3/Caspase-1介导的细胞焦亡,降低CK-MB、LDH的活性,减少大鼠心肌梗死面积,阻止心肌缺血再灌注损伤进程,保护心肌组织。
Abstract:
Objective:To observe the mechanism of paeonol on myocardial ischemia-reperfusion injury(MIRI),and effects on toll like receptor 4(TLR4)and cell pyrolysis in rats.Methods:SD rats were randomly divided into sham operation group,ischemia-reperfusion group,low-dose paeonol group(15 mg/kg)and high-dose paeonol group(30 mg/kg).After drugs intervention,left anterior descending coronary were ligating for 0.5 h and reperfusion for 4 h.After reperfusion,the levels of creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH)were determined by biochemical assays.Myocardial infarct area were measured by 2,3,5-Chlorinated triphenyl tetraazazole blue(TTC)staining method.The TLR4 protein level was determined by immunohistochemistry and the nod like receptor family pyrin domain containing 3(NLRP3),IL-1β,apoptosis-associated speckle protein(ASC)and Caspase-1 in myocardial tissue were measured by Western blot.Results:Compared with the ischemia-reperfusion group,the activities of LDH and CK-MB in the low-dose paeonol group and high-dose paeonol group were decreased,the area of myocardial infarction decreased,and the levels of TLR4,NLRP3,Caspase-1,ASC,IL-1β in myocardial tissue decreased after reperfusion, difference statistically significant(all P<0.05).Above indicators in the high-dose paeonol group were lower than those in the low-dose paeonol group,difference statistically significant(all P<0.05).Conclusion:Paeonol pretreatment can inhibit TLR4 expression,down-regulate cellular pyroptosis which NLRP3/Caspase-1 mediated,reduce CK-MB and LDH activity,reduce the area of myocardial infarction,prevent progression of myocardial ischemia and reperfusion damage in rats,and protect myocardial tissue.

参考文献/References:

[1] 沈晓璞,李 冀.丹酚酸B通过Akt-eNOS通路对大鼠心肌缺血/再灌注损伤保护作用的研究[J].陕西中医,2017,38(2):271-272.
[2] Lin J,Lin H,Ma C,et al.MiR-149 aggravates pyroptosis in myocardial ischemia-reperfusion damage via silencing FoxO3[J].Med Sci Monit,2019,25(6):8733-8743.
[3] 武卫党,郭继文,张丹凤,等.五味子乙素改善糖酵解反应大鼠心肌缺血再灌注损伤实验研究[J].陕西医学杂志,2020,49(1):12-15.
[4] Shi J,Gao W,Shao F.Pyroptosis:Gasdermin-mediated programmed necrotic cell death[J].Trends Biochem Sci,2017,42(4):245-254.
[5] Wang Z,Zhang S,Xiao Y,et al.NLRP3 inflammasome and inflammatory diseases[J].Oxid Med Cell Longev,2020,20(6):406-412.
[6] 邱 珍,夏中元,周 斌,等.细胞焦亡在糖尿病心肌缺血再灌注损伤的变化及作用机制[J].武汉大学学报:医学版,2017,38(1):1-5.
[7] Yang J,Zhang XD,Yang J,et al.The cardioprotective effect of fuvastatin on ischemic injury via down-regulation of toll-like receptor 4[J].Mol Biol Rep,2011,38(5):3037-3044.
[8] 刘阳欣,赵 锋,康秉涛,等.丹皮酚药理学研究进展[J].陕西中医,2020,41(4):550-552.
[9] Liu J,Wang S,Feng L,et al.Hypoglycemic and antioxidant activi-ties of paeonol and its beneficial effect on diabetic encephalopathy in streptozotocin-induced diabetic rats[J].J Med Food,2013,16(7):577-586.
[10] Nizamutdinova IT,Jin YC,Kim JS,et al.Paeonol and paeoniflorin, the main active principles of paeonia albiflora protect the heart from myocardial ischemia/reperfusion injury in rats[J].Planta Med,2008,74(1):14-18.
[11] 黄 鑫,丁华胜.丹皮酚对大鼠心肌缺血再灌注损伤中高迁移率族蛋白B1和白细胞介素1β及心肌凋亡的影响[J].中华老年心脑血管病杂志,2019,21(5):522-524.
[12] Nazir S,Gadi I,Al-Dabet MM,et al.Cytoprotective activated protein C averts NLRP3 inflammasome-induced ischemia/reperfusion injury via mTORC1 inhibition[J]. Blood,2017,130(24):2664-2677.
[13] Sandanger O,Ranheim T,Vinge LE,et al.The NLRP3 inflammasome is up-regulated in cardiac fibroblasts and mediates myocardial ischaemia-reperfusion injury[J].Cardiovascular Research,2013,99(1):164-174.
[14] He X,Qian Y,Li Z,et al.TLR4-Upregulated IL-1β and IL-1RI promote alveolar macrophage pyroptosis and lung inflammation through an autocrine mechanism[J].Sci Rep,2016,6(1):316-323.
[15] Nystrom S,Antoine DJ,Lundback P,et al.TLR activation regulates damage -associated molecular pattern isoforms released during pyroptosis[J].EMBO Journal,2013,32(1):86-99.
[16] Nemoto S,Vallejo JG,Knuefermann P,et al.Escherichia coli LPS-induced LV dysfunction:Role of toll-like receptor-4 in the adult heart[J].Am J Physiol Heart Circ Physiol,2002,282(6):2316-2323.
[17] Hou L,Yang Z,Wang Z,et al.NLRP3/ASC-mediated alveolar macrophage pyroptosis enhances HMGB1 secretion in acute lung injury induced by cardiopulmonary by pass[J].Lab Invest,2018,98(8):1052-1064.
[18] Dong W,Zhu Q,Yang B,et al.Polychlorinated biphenyl quinone induces Caspase-1 mediated pyroptosis through induction of pro-inflammatory HMGB1-TLR4-NLRP3-GSDMD signal axis[J].Chem Res Toxicol,2019,32(6):1051-1057.
[19] Dai Y,Wang S,Chang S,et al.M2 macrophage-derived exosomes carry microRNA-148a to alleviate myocardial ischemia/reperfusion injury via inhibiting TXNIP and the TLR4/NF-κB/NLRP3 inflammasome signaling pathway[J].Journal Mol Cell Cardiol,2020,142(20):65-79.

相似文献/References:

[1]刘阳欣,赵 锋,康秉涛,等.丹皮酚药理学研究进展*[J].陕西中医,2020,(4):550.

备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(81401304); 湖北省自然科学基金资助面上项目(2019CFB621); 湖北省卫生健康委员会联合基金资助面上项目(WJ2019H219)
更新日期/Last Update: 2021-12-09