心脉隆注射液改善大鼠离体心脏心肌缺血/再灌注损伤

doi:10.16098/j.issn.0529-1356.2021.02.018

摘要/Abstract

摘要：

目的探讨心脉隆注射液对大鼠离体心脏心肌缺血/再灌注（I/R）损伤的保护作用。方法 SPF级SD大鼠60只，随机分为6组，包括假手术(sham)组、I/R处理组以及心脉隆注射液处理组（50 mg/L、100 mg/L、200 mg/L、400 mg/L），每组10只；运用Langendorff灌流系统制作大鼠离体心脏I/R损伤模型，平衡时期持续灌注K-H液，离体心脏模型缺血复灌后灌注心脉隆注射液；多导生理转换仪Lab Chart 8.0数据采集分析软件，同步记录左心室发展压(LVDP)，描记左心室内压最大上升和下降速率(±dp/dtmax)以及心率(HR)。采用生化仪检测不同组冠状动脉流出液中心肌酶学，肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、肌钙蛋白-Ⅰ（TnI）和肌红蛋白（MYO）；实时测量冠状动脉流量，运用TTC染色了解心肌梗死面积，采用Western blotting检测Bax、Bcl-2在各组中的表达。结果心脉隆注射液能够减轻心肌缺血再灌注损伤大鼠LVDP、最大上升速率+dp/dt、最大下降速率-dp/dt的下降，减少心肌缺血再灌注损伤大鼠心肌细胞酶的释放，减少心肌梗死面积，增加心脏冠状动脉流量，引起心率增快以及一定的抑制心肌凋亡作用。结论心脉隆注射液能够减轻心肌I/R损伤引起的心功能损害。

关键词: 心脉隆注射液, 离体心脏, 缺血再灌注, 损伤保护, 免疫印迹法, 大鼠

Abstract:

Objective To observe the protective effect of Xinmailong injection (XML) on myocardial ischemia reperfusion (I/R) injury in rats model. Methods The levels of SPF 60 successful acute myocardial ischemia rat models were randomly divided into control group,I/R group and XML group(Different drug concentrations 50 mg/L,100 mg/L, 200 mg/L, 400 mg/L). The control group was continuously given K-H nutrient solution for 2 hours, the other group was given respective different drug concentrations or K-H nutrient solution by Langendorff isolated heart perfusion method after ischemia 30 minutes.The following indicators were detected: Hemodynamics included heart rate (HR), left ventricular development pressure (LVDP) and ±dp/dtmax; the myocardial enzymes included creatine kinase (CK), creatine minase-MB (CK-MB), troponin-Ⅰ (Tn-Ⅰ) and myoglobin (MYO), coronary flow and myocardial infarct size were observed. The expression of Bax and Bcl-2 in each group was detected by Western blotting and immunofluorescence. Results Xinmailong injection could alleviate LVDP and ±dp/dtmax; decrease the release of CK, CK-MB, Tn-Ⅰ, MYO and the shrink area of myocardial infarction; increase the coronary flow; enhance heart rate fast and certain inhibition of myocardial apoptosis. Conclusion Xinmailong injection can alleviate the damage of cardiac function caused by myocardial ischemia/reperfusion injury.

Key words: Xinmailong injection, Isolated heart, Ischemia reperfusion, Injury protection, Western blotting, Rat

中图分类号:

R541.4

王永洁姜永良林志刘燃姜雪梅陆地孙林 . 心脉隆注射液改善大鼠离体心脏心肌缺血/再灌注损伤[J]. 解剖学报, 2021, 52(2): 277-283.

WANG Yong-jie JIANG Yong-liang LIN Zhi LIU Ran JIANG Xue-mei LU Di SUN Lin. Xinmailong injection improving myocardial ischemia reperfusion injury in isolated-heart of rats[J]. Acta Anatomica Sinica, 2021, 52(2): 277-283.

参考文献

［1］ Ibarrola J, Matilla L, MartinezMartinez E, et al. Myocardial injury after ischemia/reperfusion is attenuated by pharmacological galectin-3 inhibition［J］. Sci Rep, 2019, 9(1): 9607.

［2］ Schanze N, Bode C, Duerschmied D. Platelet contributions to myocardial ischemia/reperfusion injury［J］. Front Immunol, 2019, 10: 1260.

［3］ Zhang XH. Observation of the efficacy of Xinmailong injection in the treatment of heart failure in elderly patients with acute myocardial infarction ［J］. Chinese Journal of Integrative Medicine on Cardio-/Cerebrovascuiar Disease， 2016, 14 (1): 60-62.（in Chinese）

张晓华. 心脉隆注射液治疗高龄急性心肌梗死后心力衰竭的疗效观察［J］. 中西医结合心脑血管病杂志. 2016, 14(1): 60-62.

［4］ Liu X, Wang Y, Zhang M, et al. Ticagrelor reduces ischemia-reperfusion injury through the NF-kappaB-dependent pathway in rats［J］. J Cardiovasc Pharmacol，2019, 74(1): 13-19.

［5］ Tang XH. Progress in clinical research of Xinmailong injection on pharmacological effects and treatment of heart failure ［J］. China Journal of New Drugs，2008 (6): 461-464.（in Chinese）

唐晓鸿. 心脉隆注射液药理作用和治疗心力衰竭临床研究进展［J］. 中国新药杂志，2008(6): 461-464.

［6］ Wen- F, Yang P, Lai TT, et al. Protective effect of ginsenoside Rg1 preconditioning on isolated heart ischemia/reperfusion injury in rats ［J］. Chinese Journal of Anatomy, 2016, 39 (6): 673-677.（in Chinese）

文飞，杨萍，赖婷婷，等. 人参皂苷Rg1预处理对大鼠离体心缺血/再灌注损伤的保护作用［J］. 解剖学杂志, 2016, 39(6): 673-677.

［7］ Bell RM, Mocanu MM, Yellon DM, et al. Retrograde heart perfusion: the Langendorff technique of isolated heart perfusion［J］. J Mol Cell Cardiol, 2011, 50(6):940-950.

［8］ Zhao J, Yu H, Yan P, et al. Circulating microRNA-499 as a diagnostic biomarker for acute myocardial infarction: a meta-analysis［J］. Dis Markers, 2019, 2019:6121696.

［9］ Zhao C, Zhang B, Jiang J, et al. Up-regulation of ANXA1 suppresses polymorphonuclear neutrophil infiltration and myeloperoxidase activity by activating STAT3 signaling pathway in rat models of myocardial ischemia-reperfusion injury［J］. Cell Signal, 2019, 62:109325.

［10］ Li Y, Li Q, Zhang O, et al. miR-202-5p protects rat against myocardial ischemia reperfusion injury by downregulating the expression of Trpv2 to attenuate the Ca (2+) overload in cardiomyocytes［J］. J Cell Biochem, 2019, 120(8):13680-13693.

［11］ Luo F, Su Q. Research status and prospect of prevention and treatment for myocardial ischemia-reperfusion injury ［J］. Guangdong Medical Journal,2019,40 (2):305-307.（in Chinese）

罗峰，苏强. 心肌缺血再灌注损伤防治的研究现状及展望［J］. 广东医学. 2019, 40(2): 305-307.

［12］ Zeng LY, Qian R, Liu L. Effects of fosinopril combined with irbesartan on hemodynamics, serum myocardial enzymology and SOD, CAT and GSH-Px activities in rats with experimental myocardial ischemia-reperfusion injury ［J］. Medical Journal of West China, 2019, 31 (10): 1528-1532.（in Chinese）

曾令勇，钱冉，刘亮. 福普利联合厄贝沙坦对大鼠心肌缺血再灌注损伤血流动力学及其相关因素的影响［J］. 西部医学, 2019, 31(10): 1528-1532.

［13］ Lin R, Lin L, Jia XZ, et al. Effects of myocardial ischemia reperfusion injury on mitochondrial function and changes in energy metabolism ［J］. Guizhou Medical Journal, 2016, 40 (6): 589-590.（in Chinese）

林荣，林琳，贾兴泽，等. 心肌缺血再灌注损伤后对线粒体功能的影响和能量代谢的变化研究［J］. 贵州医药, 2016, 40(6): 589-590.

［14］ Li H, Zhang HL, Zhang Y. Clinical value of combined detection of serum myocardium enzymogram, cTnI, MYO and BNP in early diagnosis of acute myocardial infarction ［J］. Labeled Immunoassays and Clinical Medicine, 2017, 24 (2): 167-170.（in Chinese）

李红，张海玲，张莹. 血清心肌酶谱、肌钙蛋白Ⅰ、肌红蛋白与脑钠肽的联合检测对临床诊断急性心肌梗死的意义［J］. 标记免疫分析与临床, 2017, 24(2): 167-170.

［15］ Zhao X, Liang P, Si ML, et al. Effects of ulinastatin on myocardial enzyme spectrum, inflammatory state and reperfusion injury in patients with cardiopulmonary bypass ［J］. Journal of Clinical and Experimental Medicine, 2016, 15 (19): 1913-1916.（in Chinese）

赵旭，梁平，思美丽，等. 乌司他丁对体外循环患者心肌酶谱、炎性状态及再灌注损伤的影响研究［J］. 临床和实验医学杂志, 2016, 15(19): 1913-1916.

［16］ Zeng W, Cao Y, Jiang W, et al. Knockdown of Sfrp4 attenuates apoptosis to protect against myocardial ischemia/reperfusion injury［J］. J Pharmacol Sci, 2019, 140(1):14-19.

［17］ Yu L, Zhang W, Huang C, et al. Cheng X. FoxO4 promotes myocardial ischemia-reperfusion injury: the role of oxidative stress-induced apoptosis ［J］. Am J Transl Res, 2018, 10(9):2890-2900.

［18］ Liu SD, Meng WX, Xu L, et al. GAS5 promotes myocardial apoptosis in myocardial ischemia-reperfusion injury via upregulating LAS1 expression ［J］. Eur Rev Med Pharmacol Sci, 2018, 22(23):8447-8453.

［19］ Tian BP, Li F, Li R, et al. Shen H. Nanoformulated ABT-199 to effectively target Bcl-2 at mitochondrial membrane alleviates airway inflammation by inducing apoptosis ［J］. Biomaterials, 2019, 192:429-439.

［20］ Kim HJ, Kang S, Kim DY, et al. Diallyl disulfide (DADS) boosts TRAIL-Mediated apoptosis in colorectal cancer cells by inhibiting Bcl-2［J］. Food Chem Toxicol, 2019, 125:354-360.

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