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PKC-ERK1/2通路在臭氧预处理减轻大鼠肝缺血再灌注损伤的作用

Effects of PKC-ERK1/2 Pathway on O_(3) Oxidative Pretreatment to Reduce Hepatic Ischemia Reperfusion Injury in Rats
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摘要 目的探讨PKC介导的ERK1/2信号通路在臭氧(ozone,O_(3))预处理大鼠肝缺血再灌注中的作用。方法60只大鼠随机分成6组:对照组、缺血再灌注组、O_(3)预处理组、O_(3)预处理+ERK抑制剂组(O_(3)+PD98059组)、O_(3)预处理+PKC抑制剂组(O_(3)+CHE组)、缺血再灌注+PKC激活剂组(IR+PMA组)。除对照组外,其余各组均进行肝缺血再灌注手术。O_(3)相关组予O_(3)预处理,调节剂组予相应的调节剂。分别检测各组的血清中丙氨酸氨基转移酶、天冬氨酸氨基转氨酶水平,进行病理学观察,Western blotting检测肝组织中的热休克蛋白70(heat shock protein 70,HSP70)、蛋白激酶C(protein kinase C,PKC)和细胞外调节蛋白激酶1/2(extracellular regulated protein kinases,ERK1/2)的表达水平。结果与对照组相比,缺血再灌注组肝组织细胞损伤明显加重(P<0.05),肝组织中PKC、ERK1/2的磷酸化和HSP70的表达水平明显升高(P<0.05)。与缺血再灌注组相比,O_(3)相关组肝组织细胞损伤明显减轻(P<0.05),肝组织中PKC、ERK1/2的磷酸化和HSP70的表达水平明显升高(P<0.05)。与O_(3)预处理组相比,当使用PKC和ERK1/2抑制剂后,肝组织细胞损伤明显加重(P<0.05),肝组织中PKC、ERK1/2的磷酸化和HSP70的表达水平明显降低(P<0.05)。结论O_(3)氧化预处理可通过激活PKC介导的ERK1/2信号通路,使HSP70的表达水平明显增加,使大鼠肝脏缺血再灌注损伤明显减轻。 OBJECTIVE To explore the role of PKC-mediated ERK1/2 signaling pathway in ozone(O_(3))preconditioning rat liver ischemia-reperfusion.METHODS Sixty rats were randomly divided into 6 groups:control group,ischemia reperfusion group,O_(3)pretreatment group,O_(3)pretreatment+ERK inhibitor group(O_(3)+PD98059 group),O_(3)pretreatment+PKC inhibitor group(O_(3)+CHE group),ischemia reperfusion+PKC activator group(IR+PMA group).Except for control group,all other groups underwent liver ischemia reperfusion surgery.The O_(3)-related group was pretreated with O_(3),and the regulator group was given the corresponding regulator.The levels of alanine aminotransferase and aspartate aminotransferase in serum of each group were detected respectively,and pathological observation was performed.Western blotting was used to detect heat shock protein 70(HSP70),protein kinase C(PKC)and extracellular regulated protein kinase 1/2(ERK1/2)expression levels in liver tissue.RESULTS Compared with the control group,ischemia reperfusion group had significantly increased liver tissue cell damage(P<0.05),and the PKC and ERK1/2 phosphorylation and HSP70 expression levels in the liver tissue were significantly increased(P<0.05).Compared with the ischemia reperfusion group,the liver tissue cells of the O_(3)-related group were significantly reduced(P<0.05),the phosphorylation of PKC and ERK1/2 and the expression level of HSP70 in the liver tissue were significantly increased(P<0.05).Compared with the O_(3)pretreatment group,when PKC and ERK1/2 inhibitors were used,liver tissue cell damage was significantly increased(P<0.05),PKC and ERK1/2 phosphorylation and HSP70 expression levels in liver tissue were significantly reduced(P<0.05).CONCLUSION O_(3)oxidative pretreatment can significantly increase the expression level of HSP70 by activating the PKC-mediated ERK1/2 signaling pathway,and significantly reduce the liver ischemia-reperfusion injury in rats.
作者 陶振云 江祖泰 李丽珍 王兰兰 钟炜昕 李粮辉 刘俊乐 陈文华 TAO Zhenyun;JIANG Zutai;LI Lizhen;WANG Lanlan;ZHONG Weixin;LI Lianghui;LIU Junle;CHEN Wenhua(Yiwu Central Hospital,Yiwu 322000,China;Fuzhou Second Hospital,Fuzhou 350007,China;Fujian Provincial People’s Hospital,Fuzhou 350001,China;Fujian Cancer Hospital,Fuzhou 350001,China;Fujian Medical University Mengchao Hospital,Fuzhou 350025,China;South Hospital of Fujian Provincial Hospital,Fuzhou 350028,China;Fujian Medical University Union Hospital,Fuzhou 350001,China)
出处 《中国现代应用药学》 CAS CSCD 北大核心 2021年第12期1436-1440,共5页 Chinese Journal of Modern Applied Pharmacy
基金 福建省自然科学基金项目(2016J01543)。
关键词 细胞外调节蛋白激酶1/2 热休克蛋白70 蛋白激酶C 臭氧 缺血再灌注 extracellular regulated protein kinases(ERK1/2) heat shock protein 70(HSP70) protein kinase C(PKC) ozone(O_(3)) ischemia-reperfusion
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  • 1张蕾,张文同,李燕,陈雨信,寿楠海,谭国华.一种新的大鼠肝脏热缺血再灌注模型的建立[J].临床小儿外科杂志,2005,4(5):349-353. 被引量:2
  • 2陈皓,邱伟华,邓侠兴,沈柏用,杨卫平,彭承宏,李宏为.大鼠肝脏热缺血-再灌注损伤中HSP 72对肝细胞的保护作用[J].中国微循环,2006,10(5):318-321. 被引量:7
  • 3Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium.Circulation 1986; 74:1124-1136.
  • 4Baxter GF, Marber MS, Patel VC, Yellon DM. Adenosine receptor involvement in a delayed phase of myocardial protection 24 h after ischemic preconditioning. Circulation 1994; 90:2993-3000.
  • 5Armstrong SC, Hoover DB, Delacey MH, Ganote CE. Translocation of PKC, protein phosphatase inhibition and preconditioning of rabbit cardiomyocytes. J Mol Cell Cardiol 1996; 28:1479-1492.
  • 6Baines CP, Liu GS, Birincioglu M, Critz SD, Cohen MV, Downey JM. Ischemic preconditioning depends on interaction between mitochondrial KATP channels and actin cytoskeleton. Am J Physiol Heart Circ Physiol 1999; 276:H1361-H1368.
  • 7Goto M, Liu Y, Yang XM, Ardell JL, Cohen MV, Downey JM.Role of bradykinin in protection of ischemic preconditioning in rabbit hearts. Circ Res 1995; 77:611-621.
  • 8Bogoyevltch MA, Gillespie-Brown J, Ketterman AJ, Fuller SJ,Ben-Levy R, Ashworth A, Marshall CJ, Sugden PH. Stimulation of the stress-activated mitogen activated protein kinase subfamilies in perfused heart. Circ Res 1996; 79:162-173.
  • 9Mizukami Y, Yoshida K. Mitogen-activated protein kinase translocates to the nucleus during ischemica and is activated during reperfusion. Biochem J 1997; 323:785-790.
  • 10Boulton TG,Nye SH,Robbins DJ,Ip NY,Radziejewska E,Morgenbesser SD, DePinho RA, Panayotatos N, Cobb MHIYancopoulos GD. ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell 1991; 65:663-675.

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