姜黄素对心肌梗死后血流动力学及心肌基质金属蛋白酶-2表达的影响
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摘要
目的研究姜黄素对心肌梗死大鼠的血流动力学以及基质金属蛋白酶-2(matrix metallo proteinases-2,MMP-2)表达的影响。方法将70只Sprague-Dawley成年雄性大鼠(250~300g),随机分为假手术组(n=15)和心肌梗死组(n=55),假手术组手术方式:左冠状动脉前降支处穿线并且打结,但是不阻断血流。心肌梗死组手术方式:结扎左冠状动脉前降支,阻断其冠状动脉的血流。24小时以后心肌梗死组进行随机分为:对照组、溶剂组和姜黄素组。姜黄素组腹腔注射姜黄素100mg/(kg·d),溶剂组腹腔注射相等容量的6%乙醇和6%聚乙二醇混合液。28天后用MP150型多通道生理信号采集处理系统测大鼠的左心室的舒张期末压、收缩压、最大变化速率、最小变化速率、平均动脉压。进行HE染色显微镜下观察大鼠心肌的形态学变化。采用免疫组化技术检测大鼠心肌MMP-2的表达情况。结果对照组和姜黄素组比较显示,姜黄素组收缩压、最大变化速率、最小变化速率明显提高,左心室的舒张期末压明显减低(P<0.05)。免疫组化结果显示,姜黄素可显著降低心肌MMP-2的表达(P<0.05)。HE染色显示,梗死后正常心肌细胞梗死后消失,取而代之的是胶原蛋白。结论姜黄素可在一定程度上改善心肌梗死大鼠心脏功能,抑制MMP-2表达。
Objective The present study was designed to examine the effects of curcumin on hemodynamics and matrix metallo proteinases-2( MMP-2) expression in myocardial infarction rats. Method 70 cases Sprague-Dawley healthy adult male rats( 250 ~ 300g) were randomly divided into sham operation group( n = 15) and miocardial infarction group( MI,n = 55). The mode of operation was that the line in left anterior descending coronary artery threading and knotting but not to block the blood flow had used for sham operation group. MI group was established by ligation of left anterior descending branch of coronary artery and the sham operation group( sham) rats underwent the same procedure without ligation. 24 hours later,the MI group was further sub-divided into 3 groups: control group,solvent group and curcumin group. The solvent group was treated with only solvent( a blend which blend Polyethylene glycol,alcohol and water) and curcumin group was intraperitoneally administered with curumin at 100 mg /kg / d for 28 days. MP150 type multichannel physiological functions signal collection processing system was used to test left ventricular end diastolic pressure( LVDEP),systolic pressure( SYS),maximum change in pressure over the cycle( dp / dtmax),minimum change in pressure over the cycle( dp/dtmin) and mean blood pressure( MBP).HE staining was employed to detect the morphological changes of cardiomyocytes. Moreover,the expression of MMP-2 protein in the myocardium of the rats was tested by immunohistochemical technique. Result SYS,dp / dtmax and dp / dtminwere significantly increased while the LVDEP decreased in the curcumin group compared with control( P < 0. 05). Immunohistochemistry revealed a decrease in expression of MMP2 in curcumin group compared to contral and solvent groups( P < 0. 05). HE staining revealed that some normal cardiac myocytes were disappeared after MI,and were replaced by collagens. Conclusion Our study revealed that curcumin ameliorated hemodynamics and inhibit MMP-2 expression post myocardial infarction in rats.
Objective The present study was designed to examine the effects of curcumin on hemodynamics and matrix metallo proteinases-2( MMP-2) expression in myocardial infarction rats. Method 70 cases Sprague-Dawley healthy adult male rats( 250 ~ 300g) were randomly divided into sham operation group( n = 15) and miocardial infarction group( MI,n = 55). The mode of operation was that the line in left anterior descending coronary artery threading and knotting but not to block the blood flow had used for sham operation group. MI group was established by ligation of left anterior descending branch of coronary artery and the sham operation group( sham) rats underwent the same procedure without ligation. 24 hours later,the MI group was further sub-divided into 3 groups: control group,solvent group and curcumin group. The solvent group was treated with only solvent( a blend which blend Polyethylene glycol,alcohol and water) and curcumin group was intraperitoneally administered with curumin at 100 mg /kg / d for 28 days. MP150 type multichannel physiological functions signal collection processing system was used to test left ventricular end diastolic pressure( LVDEP),systolic pressure( SYS),maximum change in pressure over the cycle( dp / dtmax),minimum change in pressure over the cycle( dp/dtmin) and mean blood pressure( MBP).HE staining was employed to detect the morphological changes of cardiomyocytes. Moreover,the expression of MMP-2 protein in the myocardium of the rats was tested by immunohistochemical technique. Result SYS,dp / dtmax and dp / dtminwere significantly increased while the LVDEP decreased in the curcumin group compared with control( P < 0. 05). Immunohistochemistry revealed a decrease in expression of MMP2 in curcumin group compared to contral and solvent groups( P < 0. 05). HE staining revealed that some normal cardiac myocytes were disappeared after MI,and were replaced by collagens. Conclusion Our study revealed that curcumin ameliorated hemodynamics and inhibit MMP-2 expression post myocardial infarction in rats.
引文
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[12]韩振,孙雪林,赵玉,等.糖化血红蛋白水平与急性心肌梗死患者冠状动脉病变程度相关性研究[J].中国临床医生,2012,40(1)∶45-46.
[13]吴强,王楚林,林宇鹏,等.大剂量或小剂量阿托伐他汀对ST段抬高型心肌梗死患者急诊经皮冠状动脉介入术后无复流现象的影响[J].中国医药,2014,(9)∶1262-1266.
[14]Shimizu N,Yoshiyama M,Takeuchi K,et al.Doppler echocardiographic assessment and cardiac gene expression analysis of the left ventricle in myocardial infarcted rats[J].Japanese circulation journal,1998,62(6)∶436-442.
[15]Peterson JT,Li H,Dillon L,et al.Evolution of matrix metallo protease and tissue inhibitor expression during heart failure progression in the infarcted rat[J].Cardiovascular research,2000,46(2)∶307-315.
[16]Chen J,Tung CH,Allport JR,et al.Near-infrared fluorescent imaging of matrix metallo proteinase activity after myocardial infarction[J].Circulation,2005,111(14)∶1800-1805.
[17]Cheung PY,Sawicki G,Wozniak M,et al.Matrix metallo proteinase-2 contributes to ischemia-reperfusion injury in the heart[J].Circulation,2000,101(15)∶1833-1839.
[18]Falk V,Soccal PM,Grünenfelder J,et al.Regulation of matrix metallo proteinases and effect of MMP-inhibition in heart transplant related reperfusion injury[J].Eur J Cardiothorac Surg,2002,22(1)∶53-58.
[2]Lin HJ,Su CC,Lu HF,et al.Curcumin blocks migration and invasion of mouse-rat hybrid retina ganglion cells(N18)through the inhibition of MMP-2,-9,FAK,Rho A and Rock-1 gene expression[J].Oncology reports,2010,23(3)∶665.
[3]Ghosh SS,Salloum FN,Abbate A,et al.Curcumin prevents cardiac remodeling secondary to chronic renal failure through deactivation of hypertrophic signaling in rats[J].Am J Physiol Heart Circ Physiol,2010,299(4)∶H975-H984.
[4]Smith MR,Gangireddy SR,Narala VR,et al.Curcumin inhibits fibrosis-related effects in IPF fibroblasts and in mice following bleomycin-induced lung injury[J].Am J Physiol Lung Cell Mol Physiol,2010,298(5)∶L616-L625.
[5]Kilkenny C,Browne W,Cuthill IC,et al.Animal research:reporting in vivo experiments:the ARRIVE guidelines[J].Br J Pharmacol,2010,160(7)∶1577-1579.
[6]Li X,Han J,Li L,et al.Effect of farnesyltransferase inhibition on cardiac remodeling in spontaneously hypertensive rats[J].International journal of cardiology,2013,168(4)∶3340-3347.
[7]Hayashidani S,Tsutsui H,Ikeuchi M,et al.Targeted deletion of MMP-2 attenuates early LV rupture and late remodeling after experimental myocardial infarction[J].American Journal of PhysiologyHeart and Circulatory Physiology,2003,285(3)∶H1229-H1235.
[8]Mc Cormick RJ,Musch TI,Bergman BC,et al.Regional differences in LV collagen accumulation and mature cross-linking after myocardial infarction in rat[J].American Journal of Physiology,1994,266(1Pt2)∶H354.
[9]Zhao ZQ,Corvera JS,Halkos ME,et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion:comparison with ischemic preconditioning[J].Am J Physiol Heart Circ Physiol,2003,285(2)∶H579-H588.
[10]Spinale FG,Gunasinghe H,Sprunger PD,et al.Extracellular degradative pathways in myocardial remodeling and progression to heart failure[J].J Card Fail,2002,8(6Suppl)∶S332-S338.
[11]蔡丽霞,樊国峰,董巍,等.胸前导联心电图变化与急性下壁心肌梗死相关动脉关系的临床研究[J].中国医刊,2012,47(3)∶53-55.
[12]韩振,孙雪林,赵玉,等.糖化血红蛋白水平与急性心肌梗死患者冠状动脉病变程度相关性研究[J].中国临床医生,2012,40(1)∶45-46.
[13]吴强,王楚林,林宇鹏,等.大剂量或小剂量阿托伐他汀对ST段抬高型心肌梗死患者急诊经皮冠状动脉介入术后无复流现象的影响[J].中国医药,2014,(9)∶1262-1266.
[14]Shimizu N,Yoshiyama M,Takeuchi K,et al.Doppler echocardiographic assessment and cardiac gene expression analysis of the left ventricle in myocardial infarcted rats[J].Japanese circulation journal,1998,62(6)∶436-442.
[15]Peterson JT,Li H,Dillon L,et al.Evolution of matrix metallo protease and tissue inhibitor expression during heart failure progression in the infarcted rat[J].Cardiovascular research,2000,46(2)∶307-315.
[16]Chen J,Tung CH,Allport JR,et al.Near-infrared fluorescent imaging of matrix metallo proteinase activity after myocardial infarction[J].Circulation,2005,111(14)∶1800-1805.
[17]Cheung PY,Sawicki G,Wozniak M,et al.Matrix metallo proteinase-2 contributes to ischemia-reperfusion injury in the heart[J].Circulation,2000,101(15)∶1833-1839.
[18]Falk V,Soccal PM,Grünenfelder J,et al.Regulation of matrix metallo proteinases and effect of MMP-inhibition in heart transplant related reperfusion injury[J].Eur J Cardiothorac Surg,2002,22(1)∶53-58.