维生素E对大鼠肾缺血再灌注后心肌损伤的影响
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摘要
目的探讨维生素E(vitamin E,VE)对大鼠肾缺血再灌注(renal ischemia reperfusion,RIR)后心肌损伤的影响。方法复制大鼠RIR模型,部分动物再灌注前4周灌胃给予VE 500 mg/kg/24 h,观察心肌组织丙二醛(MDA)、髓过氧化物酶(MPO)、黄嘌呤氧化酶(XO)、超氧化物歧化酶(SOD)、一氧化氮(NO)和血浆肌酸激酶(CK)和肌酸激酶同工酶(CK-MB)的变化;测定平均动脉压(MAP)、左心室收缩压(LVSP)、收缩期左室内压上升最大速率(dp/dtmax)和舒张期左室内压下降最大速率(-dp/dtmax);光镜、免疫组化观察心肌形态和内皮型一氧化氮合酶(e NOS)的表达。Western blot法检测心肌细胞P47phox蛋白表达。结果大鼠RIR后,心肌组织MDA含量、MPO和XO活性及NO浓度增加而SOD活性减少,血浆CK、CK-MB升高,血流动力学指标下降,镜下心肌细胞水肿、e NOS阳性细胞数增加,p47phox蛋白表达增多;给予VE后,大鼠心肌组织中MDA含量、MPO和XO活性降低而SOD活性增加,血浆CK、CK-MB下降,血流动力学指标升高,NO浓度升高,镜下心肌损伤减轻,e NOS阳性细胞数增多,p47phox蛋白表达减少,差异均具有统计学意义。结论 VE可能通过抗炎、抗氧化、升高NO含量、减少P47phox表达等途径对RIR后的心肌发挥保护作用。
Objective To investigate the effect of vitamin E( VE) on myocardium in a rat model of renal ischemia reperfusion( RIR). Methods Rats were divided into three groups: a control group,RIR model group,and experimental( VE + RIR) group fed with VE for 4 weeks before the RIR model was prepared. Contents of malondialdehyde( MDA),myeloperoxidase( MPO),xanthine oxidase( XO),superoxide dismutase( SOD),and nitric oxide( NO) were measured in the myocardium. In addition,levels of creatine kinase( CK) and creatine kinase MB isoenzyme( CK-MB) in plasma were determined. Mean arterial pressure( MAP),left ventricular systolic pressure( LVSP),maximal rise rate of left ventricular pressure( d P/dtmax) and maximal fall rate of left ventricular pressure(-d P/dtmax) were monitored.Myocardial cell morphology and expression of endothelial nitric oxide synthase( e NOS) were observed by light microscopy and immunohistochemistry. Western blot analysis was conducted to quantify P47 phox expression in cardiomyocytes. Results Compared with the control group,levels of MDA,MPO,XO,and NO were increased,and the level of SOD was decreased in the myocardium of RIR group rats; moreover,CK and CK-MB plasma levels were increased in this group.Compared with the control group,values of MAP,LVSP,d P/dtmax,and-d P/dtmaxwere obviously decreased in the RIR group. In addition,aggravation of myocardial damage,number of e NOS-positive cells,and P47 phox protein expression were increased in the RIR group compared with the control group. Compared with RIR group,the VE + RIR group exhibited decreased levels of MDA,MPO,and XO,as well as increased levels of SOD increased in myocardium. In addition,plasma levels of CK and CK-MB were decreased,NO content was increased,and values of MAP,LVSP,d P/dtmax,and-d P/dtmax were obviously increased in the VE + RIR group compared with the RIR group. Moreover,compared with the RIR group,microscopic cardiomyocyte injury was reduced,numbers of e NOS-positive cells were increased,and P47 phox protein expression was decreased in the VE + RIR group. Conclusions VE potentially protects the myocardium from RIR by antiinflammatory and anti-oxidative mechanisms, as well as by increasing NO content and decreasing P47 phox protein expression.
Objective To investigate the effect of vitamin E( VE) on myocardium in a rat model of renal ischemia reperfusion( RIR). Methods Rats were divided into three groups: a control group,RIR model group,and experimental( VE + RIR) group fed with VE for 4 weeks before the RIR model was prepared. Contents of malondialdehyde( MDA),myeloperoxidase( MPO),xanthine oxidase( XO),superoxide dismutase( SOD),and nitric oxide( NO) were measured in the myocardium. In addition,levels of creatine kinase( CK) and creatine kinase MB isoenzyme( CK-MB) in plasma were determined. Mean arterial pressure( MAP),left ventricular systolic pressure( LVSP),maximal rise rate of left ventricular pressure( d P/dtmax) and maximal fall rate of left ventricular pressure(-d P/dtmax) were monitored.Myocardial cell morphology and expression of endothelial nitric oxide synthase( e NOS) were observed by light microscopy and immunohistochemistry. Western blot analysis was conducted to quantify P47 phox expression in cardiomyocytes. Results Compared with the control group,levels of MDA,MPO,XO,and NO were increased,and the level of SOD was decreased in the myocardium of RIR group rats; moreover,CK and CK-MB plasma levels were increased in this group.Compared with the control group,values of MAP,LVSP,d P/dtmax,and-d P/dtmaxwere obviously decreased in the RIR group. In addition,aggravation of myocardial damage,number of e NOS-positive cells,and P47 phox protein expression were increased in the RIR group compared with the control group. Compared with RIR group,the VE + RIR group exhibited decreased levels of MDA,MPO,and XO,as well as increased levels of SOD increased in myocardium. In addition,plasma levels of CK and CK-MB were decreased,NO content was increased,and values of MAP,LVSP,d P/dtmax,and-d P/dtmax were obviously increased in the VE + RIR group compared with the RIR group. Moreover,compared with the RIR group,microscopic cardiomyocyte injury was reduced,numbers of e NOS-positive cells were increased,and P47 phox protein expression was decreased in the VE + RIR group. Conclusions VE potentially protects the myocardium from RIR by antiinflammatory and anti-oxidative mechanisms, as well as by increasing NO content and decreasing P47 phox protein expression.
引文
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[14]张卫强,王涛,张志明,等.大鼠心肌缺血再灌注损伤模型的改进与评判[J].中国实验动物学报,2018,26(03):311-316.
[15] Feng W,Jin L,Xie Q,et al. Eugenol protects the transplanted heart against ischemia/reperfusion injury in rats by inhibiting the inflammatory response and apoptosis[J]. Exp Ther Med,2018,16(4):3464-3470.
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[17]刘雨娟,单芳,黄瑞萍,等.不同剂量H2S对大鼠肾缺血再灌注所致心肌损伤的保护作用研究[J].中国现代医学杂志,2015,25(04):21-24.
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[20]陈晖,刘修恒,王磊,等.缺血后处理对肾缺血/再灌注损伤后内皮型一氧化氮合酶表达的影响[J].医学综述,2013,19(18):3372-3376.
[21] Song Y,Yu Q,Zhang J. et al. Increased myocardial ischemiareperfusion injury in renal failure involves cardiac adiponectin signal deficiency[J].Am J Physiol Endocrinol Metab,2014,306(9):1055-1064.
[22]荆娇,牛丽静,王慧娟,等.辛伐他汀对肾缺血再灌注损伤大鼠肾组织p47phox表达的影响[J].中国病理生理杂志,2015,31(10):1905.
[2]李新灵,雷钟,杜靖,等.不同剂量右美托咪定对大鼠肾缺血再灌注后心肌组织损伤的影响[J].医学研究生学报,2015,28(08):809-814.
[3]王晓燕,金春华.维生素E在新生儿的临床应用进展[J].医学综述,2017,23(5):953-956+961.
[4]侯文彬,许艳萍.维生素E功能研究进展[J].中国医学工程,2015,23(02):199+201.
[5]张红梅,李海朝,文自翔,等.大豆籽粒维生素E含量QTL分析[J].作物学报,2015,41(02):187-196.
[6] Zhen Y,Ding C,Sun J,et al. Activation of the calcium-sensing receptor promotes apoptosis by modulating the JNK/p38 MAPK pathway in focal cerebral ischemia-reperfusion in mice[J]. Am J Transl Res,2016,8(2):911-921.
[7] Yang Y,Song M,Liu Y,et al. Renoprotective approaches and strategies in acute kidney injury[J]. Pharmacol Ther,2016,7(163):58-73.
[8] Duann P,Lianos EA,Ma J,et al. Autophagy,innate immunity and tissue repair in acute kidney injury[J]. Int J Mol Sci,2016,17(5):E662-E662.
[9] Pan JS,Huang L,Belousova T,et al. Stanniocalcin-1 inhibits renal ischemia/reperfusion injury via an AMP-activated protein kinase-dependent pathway[J]. J Am Soc Nephrol,2015,26(2):364-78.
[10] Yao M, Rogers M, Csanyi G, et al. Thrombospondin-1activation of signal-regulatory protein-alpha stimulates reactive oxygen species production and promotes renal ischemia reperfusion injury[J]. J Am Soc Nephrol,2014,25(6):1171-1186.
[11] Rahmania L, Orbegozo D, Su F, et al. Administration of tetrahydrobiopterin(bh4)protects the renal microcirculation from ischemia and reperfusion injury[J]. Anesth Analg,2017,125(4):1253-1260.
[12]荆娇,马海玲,闫文升,等.辛伐他汀对肾缺血再灌注损伤大鼠心肌细胞凋亡的影响[J].中西医结合心血管病电子杂志,2017,5(21):170-171.
[13] Li J,Zhang Y,Luan H,et al. L-carnitine protects human hepatocytes from oxidative stress-induced toxicity through Aktmediated activation of Nrf2 signaling pathway[J]. Can J Physiol Pharmacol,2016,94(5):517-525.
[14]张卫强,王涛,张志明,等.大鼠心肌缺血再灌注损伤模型的改进与评判[J].中国实验动物学报,2018,26(03):311-316.
[15] Feng W,Jin L,Xie Q,et al. Eugenol protects the transplanted heart against ischemia/reperfusion injury in rats by inhibiting the inflammatory response and apoptosis[J]. Exp Ther Med,2018,16(4):3464-3470.
[16] Wang Q,Lin P,Li P,et al. Ghrelin protects the heart against ischemia/reperfusion injury via inhibition of TLR4/NLRP3inflammasome pathway[J]. Life Sci,2017,186(1):50-58.
[17]刘雨娟,单芳,黄瑞萍,等.不同剂量H2S对大鼠肾缺血再灌注所致心肌损伤的保护作用研究[J].中国现代医学杂志,2015,25(04):21-24.
[18] Yamasowa H,Shimizu S,Inoue T,et al. Endothelial nitric oxide contributes to the renal protective effects of ischemic preconditioning[J]. J Pharmacol Exp Ther,2005,312(1):153-159.
[19] Torras J,Herrero-Fresneda I,Lloberas N,et al. Novel potentials of the DPP-4 inhibitor sitagliptin against ischemia-reperfusion(I/R)injury in rat ex-vivo heart model[J]. Int J Mol Sci,2018,19(10):pii:E3226.
[20]陈晖,刘修恒,王磊,等.缺血后处理对肾缺血/再灌注损伤后内皮型一氧化氮合酶表达的影响[J].医学综述,2013,19(18):3372-3376.
[21] Song Y,Yu Q,Zhang J. et al. Increased myocardial ischemiareperfusion injury in renal failure involves cardiac adiponectin signal deficiency[J].Am J Physiol Endocrinol Metab,2014,306(9):1055-1064.
[22]荆娇,牛丽静,王慧娟,等.辛伐他汀对肾缺血再灌注损伤大鼠肾组织p47phox表达的影响[J].中国病理生理杂志,2015,31(10):1905.