《Tau和GR减轻IR诱导的大鼠心肌氧化应激损伤机制研究》由会员分享，可在线阅读，更多相关《Tau和GR减轻IR诱导的大鼠心肌氧化应激损伤机制研究（63页珍藏版）》请在金锄头文库上搜索。
1、天津医科大学硕士学位论文中文摘要目的：研究渐增再灌注(gradual reperfusion，GR)和牛磺酸(Taurine，Tau)对缺血 再灌(IP)诱导的大鼠离体心肌氧化损伤的保护作用，探讨该作用是否与Akt 和Erk信号通路有关。方法：采用Langendor躏体心脏灌流法制备离体大鼠心肌缺血再灌注模型。SD大鼠随机分为7组：正常对照组(Nor)，缺血再灌注组(tR)，渐增再灌注组(GR)， Tau低浓度组(T20)，Tau高浓度组(Z40)，渐增再灌注联合1au低浓度组(GT20)， 渐增再灌注联合Tau高浓度组(GT40)。记录心功能指标，包括：左室发展压 (LVDP)、左室内压上升
2、最大速度(+dpdtm强)、左室内压下降最大速度(一dpdtm戤) 及冠脉流量(CF)；TTC染色法测定心肌梗死面积；检测冠脉流出液中乳酸脱氢 酶(LDH)的活性；HE染色观察心肌形态学的改变；比色法测定总超氧化物歧 化酶(total superoxide dismutase，T-SOD)和Mn超氧化物歧化酶(manganese superoxide dismutase，MnSOD)活力以及丙二醛(malondialdehyde，MDA)含 量；Western blot检测心肌组织中Akt和Erk蛋白的磷酸化水平。结果：1GR和Tau减轻I瓜诱导的大鼠离体心肌氧化损伤 与IR组比较，GR组、G
3、T20组和GT40组显著提高LVDP、+dpdtmax$口dpdtmax，减少梗死面积，降低LDH，减轻心肌形态学损伤。与FR组比较，GR组、GT20组、GT40组可以显著提高TSOD(124261249。140761036。163131630 VS10068786，P001)和MnSOD(7486703，8165702，9631 703 VS4806511，P001)，降低MDA(198016，186011，137O15 VS228018P001)。2GR和Tau可能通过Akt通路减轻IR诱导的大鼠离体心肌氧化损伤Western blot结果显示，与I爪组比较， GR组、GT20组、GT40
4、组均可显 著上调心肌组织中p-Akt蛋白表达水平沪001)，但p-Erk蛋白表达水平没有统 计学差异。结论：1GR增加大鼠心肌冠脉流量，减少缺血的梗死面积，降低LDH，减轻心肌天津医科大学硕士学位论文形态学损伤，可以显著提高TSOD和MnSOD含量，降低MDA含量，减轻氧化 应激损伤，促进心肌的功能恢复。Tau增加大鼠心肌冠脉流量，减少缺血的梗死 面积，降低LDH，减轻心肌形态学损伤，可以显著提高TSOD和MnSOD含量， 降低MDA含量，减轻氧化应激损伤，促进心功能恢复。Tau预适应联合GR对缺 血心肌有更好的保护作用，其强度强于单用GR或Tau。2Tau和GR提高缺血心肌Akt的磷酸化。T
5、au和GR可能通过Akt通路减轻IR 诱导的大鼠离体心肌氧化损伤。关键词：牛磺酸渐增再灌注心功能氧化应激SODMDAAkt信号通路天津医科大学硕士学位论文 Abst ractobiective：To study protective effects of the taurine(Tau)and gradual reperfusion(GR) reduced IR-induced rats oxidative damage in vitro，and to explore whether through the Akt and the Erk signal pmhwayMethods：Isolat
6、ed myocardial ischemia-reperfusion(IR)model was replicated by Langendorff perfused rat heartSpragueDawley rats were randomLy divided into seven groups：normal(Nor)group，IR group，GR group，taurine of lower concentration(T20)group，Tau of higher concentration(T40)group，GR combined with Tau of lower conce
7、ntration(GT20)group and GR combined with Tau of higher concentration(GT40)groupThe cardiac function was recorded，including the left ventricular developing pressure(LVDP)，+dpdtma)(，-dpdtma)【and coronary flow(CF) The LDH activity of each group and the myocardial infarct size were observed Changes of m
8、yocardial morphology were observed after HE stainingThe activity of the total superoxide dismutase(total superoxide dismutase，T-SOD)and Mn superoxide dismutase(superoxide dismutase of Mn，Mn-SOD)and the content ofmalondialdehyde(MDA)were me姗edIn the next step the Akt and Erk proteinphosphorylation le
9、vels of myocardial tissue were detected by Western blotResults：1The myocardial ischemiareperfusion induced oxidative injury was reduced byTau and GRCompared“th IR group，the LVDP,+dpdt max，-dpdtmax were significantly improved，the CF was significantly decreased after 90rain reperfusion，LDH and myocard
10、ial infarct size were decreased significantly in GR，GT20，and GT40 groups Compared with the IR group，the T-SOD(12426士1249，14076 4-1036，16313 4- 1 630 VS1 0068-4-786，P00 1)and MnSOD(7486 4-703，8 165 4-702，963 1士703 VS4806 4-511，P00 1)content were significantly improved and MDA(198士 016，186 4-01l，137 4
11、-O15 VS228士018，P005，PO01)content was decreased in GR，GT20 and GT40 groups2The Akt pathway may be activated in the myocardial protective effects of GR and Tau reduced IRinduced oxidative injury in vitroWestern blot showed that P-Akt protein expression levels in myocardial tissue(P001)was significantl
12、y increased in the GR，GT20，GT40 group，but p-Erk proteinIII天津医科大学硕士学位论文expression level was not statistically different Conclusion：1The myocardial coronary flow was increased and the myocardial infarct size wasreduced by GR and TauThe recovery of myocardial function was promoted Oxidative stress dama
13、ge was reduced by GR and TauTau preconditioning j oint GR has a better protective effect on myocardial ischemiaThe intensity is stronger than asingle gradual perfusion or Tau2The phosphorylation of Akt was promoted by GR and TauThe Akt pathway may be activated in vitro that was the mechanisms of GR and Tau reduce IR-inducedmyocardial oxidative damageKeywo rds=taurine gradual perfusion cardiac function oxidative stress SOD MDAAkt signaling pathwayIV天津医科大学硕士学位论文VII天津医科大学硕士学位论文VIII天津医科大学硕士学位论文 月Ij吾研究现状、成果缺血再灌注损伤(ischemic reperfusion injury，IR)是指当机体组织、细胞通 过低灌流缺血后获得血液再供应时，
