单磷酰酯A预处理的心肌延迟保护作用与诱导型一氧化氮合酶及蛋白激酶C的关系
Relationship between delayed cardioprotection induced by monophosphoryl lipid A nitric oxide synthase combinded with protein kinase C
-
摘要: 目的：观察单磷酰酯A（MLA）处理后对在体兔心肌缺血再灌注（I/R）损伤的延迟保护作用，探讨诱导型一氧化氮合酶（iNOS）和蛋白激酶C（PKC）在MLA处理后心肌保护中的作用。方法：新西兰兔24只，随机分为3组（各8只）：对照组（静脉注射0.9%氯化钠溶液），MLA组（静脉注射MLA）和抑制组（多黏菌素B+静脉注射MLA）。3组动物进行I/R处理（缺血30 min，再灌注60 min），抑制组于I/R前30 min静脉注射PKC抑制剂多黏菌素B；观察MLA预处理对肌酸激酶释放、心律失常发生的作用及同iNOS表达的相关性。结果：MLA组实验兔肌酸激酶水平明显低于对照组和抑制组（P < 0.01）；MLA组未见心律失常，并可见iNOS表达积分均显著大于对照组和抑制组（P < 0.01）。3组实验兔心肌组织iNOS表达积分在缺血区与非缺血区差异均无统计学意义（P > 0.05）。结论：MLA预处理能有效减轻24 h后心肌I/R损伤，即能介导延迟保护作用。PKC可能通过调控iNOS的表达而参与此延迟保护作用。Abstract: Objective: To observe the delayed protection effects of monophosphoryl lipid A(MLA) on ischemia-reperfusion(I/R) injury in rabbits,and investigate the protect effects of inducible nitric oxide synthase(iNOS) combined with protein kinase C(PKC) on cardioprotection induced by MLA.Methods: Twenty four newsland rabbits were randomly divided into the control group(intravenous injection of 0.9 sodium chloride solution),MLA group(intravenous injection of MLA) and inhibition group(Polymyxins combined with intravenous injection of MLA).Three groups were treated with I/R( 30 min of ischemia and 60 min of reperfusion),the PKC inhibitor/Polymyxin B(PMB) was intravenously injected into the inhibition group before 30 min of I/R.The creatine kinase(CK) releasing,arrhythmia happening and expression of iNOS were measured in rabbits induced by MLA.Results: The level of CK in MLA group was significantly lower than that in control group and inhibition group(P < 0.01).The arrhythmia in MLA group was not found,and the expression integral of iNOS in MLA group was significantly more than that in control group and inhibition group(P < 0.01).The differences of the expression integral of iNOS in cardiac muscular tissue between ischemic region and non-ischemic region in 3 groups were not statistically significant(P > 0.05).Conclusions: The MLA pretreatment can effectively alleviate the I/R myocardium injury after 24 h,namely mediating the delayed protection.PKC maybe involve in the delayed protection by regulating iNOS expression.
-
[1] ANDREADOU I,BENAKI D,EFENTAKIS P,et al.The natural olive constituent oleuropein induces nutritional cardioprotection in normal and cholesterol-fed rabbits:comparison with preconditioning[J].Planta Med,2015,81(8):655. [2] 胡一冰,林玉琳,赵艳芝.国外心肌缺血/再灌注引发的细胞凋亡的治疗研究进展[J].中国医药导报,2013,10(5):32. [3] 赵志青.后适应:心肌缺血再灌注保护研究展望[J].中华高血压杂志,2012,6(20):503. [4] 李晓梅,杨毅宁,马依彤,等.再灌注抢救激酶在肥厚心肌缺血后适应中的作用[J].中华高血压杂志,2011,3(9):263. [5] YAO Z,ELLIOTT GT,GROSS GJ,et al.Monophosphoryl lipid A preserves myocardial contractile function following multiple,brief periods of coronary occlusion in dogs[J].Pharmacology,1995,51(3):152. [6] XUAN YT,TANG XL,QIU Y,et al.Biphasic response of cardiac NO synthase isoforms to ischemic preconditioning in conscious rabbits[J].Am J Physiol Heart Circ Physiol,2000,279(5):2360. [7] KHALIULIN I,CLARKE SJ,LIN H,et al.Temperature preconditioning of isolated rat hearts-a potent cardioprotective mechanism involving a reduction in oxidative stress and inhibition of the mitochondrial permeability transition pore[J].J Physiol,2007,581(Pt3):1147. [8] JONSDOTTIR S,SVANSSON V,STEFANSDOTTIR SB,et al.A preventive immunization approach against insect bite hypersensitivity:Intralymphatic injection with recombinant allergens in Alum or Alum and monophosphoryl lipid A[J].J Vet Immunol Immunopathol,2016,172:14. [9] KOLANOWSKI ST,LISSENBERG-THUNNISSEN SN,EMAL D,et al.Monophosphoryl lipid A-induced pro-inflammatory cytokine expression does not require CD14 in primary human dendritic cells[J].Inflamm Res,2016,65(6):449. [10] DITZ C,BAHLMANN L,KLAUS S,et al.Cerebral metabolism during experimental endotoxin shock and after preconditioning with monophosphoryl lipid A[J].Clin Neurol Neurosurg,2014,126:115. [11] TOSAKI A,MAULIK N,ELLIOT GT,et al.Preconditioning of rat heart with MLA:a role for nitric oxide[J].J Pharmacol Exp Ther,1998,285(3):1274. [12] ZHAO L,WEBER PA,SMITH JR,et al.Role of inducible nitric oxide synthase (iNOS) in pharmacological "preconditioning" with monophosphoryl lipid A[J].Mol Cell Cardiol,1997,29(6):1567. -
点击查看大图
计量
- 文章访问数: 4422
- HTML全文浏览量: 514
- PDF下载量: 154
- 被引次数: 0
下载:
