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尼可地尔改善心脏停搏液对心脏的保护作用

时间:2017-09-16 01:00:23 来源: 代写硕士论文

                     作者:史红宇,朱晓峰,战鹏,温福兴,龙村

【关键词】  心肌保护

    摘要:目的 观察在HTK液和UW液中加入尼可地尔(Nicorandil)对心肌保存液保存效果的影响。方法  实验分为4组:UW液(U)组 ;HTK液(H)组;UW液组+Nicorandil(U+N) 组;HTK液+Nicorandil(H+N) 组;每组8只大白鼠。麻醉和抗凝后,快速取下鼠心并悬挂在Langendorff灌注模型上灌注,测定血流动力学基础值。分别用四组保存液灌停离体鼠心并低温(4℃)浸泡保存6h。复温、复灌后再次测定血流动力学值,留取标本分别测定心肌水含量、心肌酶漏出量、心肌细胞ATP和CP含量和心肌细胞超微结构变化。结果  心肌血流动力学恢复率: H+N组>U+N组>H组>U组。心肌水含量:4组间差异无显著意义。灌脉流出液中心肌酶漏出量:H+N组<H组<U+N组<U组。心肌中ATP和CP含量:H+N组>U+N组>H组>U组。心肌细胞超微结构变化:H+N组心肌损害最轻,H组轻于U+N组,U组心肌损害最严重。结论 HTK液和UW液都是比较合适的心肌保存液,HTK液对心肌的保护作用优于UW液,钾离子通道开放剂Nicorandil 能够善器官保存液HTK液和UW液对心肌的保存效果。

  关键词:HTK液;UW液;尼可地尔;心肌保护

  The Myocardial Preservation Effect of Nicorandil in HTK Solution and UW Solution

  Abstract: OBJECTIVE  We investigated the efficacy of HTK solution and UW solution with Nicorandil(NCR) in the isolated rat heart models. METHODS   The hearts were divided into four groups:  UW solution (U ) group;  HTK solution (H ) group; UW solution with Nicorandil (U+N )group; HTK solution with Nicorandil ( H+N) group. The hearts isolated from Wistar rats were mounted on a Langendorff apparatus to estimate baseline hemodynamic values. They were arrested and stored at 4℃ in each preservation solution for 6 hours. The recovery of myocardial function were measured. Myocardial tissue water content was evaluated. Myocardial tissue Adenosine Triphosphate (ATP) and Creatine Phosphate(CP) content in each group were also measured. The leakage of myocardial enzymes were measured as well. Finally, myocardial ultrastructure was observed. RESULTS  The recovery rate of myocardial function: the group of H+N > the group of U+N > the group of H > the group of U. The myocardial tissue water content: there was no significant changes in four groups; The leakage of myocardial enzymes: the group of H+N < the group of H < the group of U+N < the group of U. The level of ATP and CP in myocardial tissue: the group of H+N > the group of U+N > the group of H > the group of U. The myocardial ultrastructure: The histological changes of myocardial cell and the damage of vascular endothelial cell were more significant in U+N group compared with that in H+N group. The histological changes were severer in U group than that in U+N  group.CONCLUSION  These results suggest that HTK solution is more effective than UW solution for myocardial preservation, and that NCR provides still better protection in the heart transplantation.

  Key words:HTK solution; UW solution; Nicorandil; Myocardial preservation
                                                      
  1967年人类首例心脏移植成功以来,心脏移植作为治疗终末期心脏疾病的唯一有效手段,其生存率逐年提高,但临床上观察,心脏移植术后30天内死亡的病例数与供体心脏保存不佳有着明显的相关性。目前,在深低温(0~4℃)的条件下,以UW液(Uinversity of Wisconsin Solution)和HTK液(Histidine-Trytophane-Ketoglutarate Solution)对心脏的保存效果为佳,但临床离体心脏保存安全时限只能达到4~6h[1],且移植后心脏功能都有不同程度的下降。如何进一步提高心脏保存液的保存效果和尽可能的延长心脏保存的安全时限是我们要解决的重要课题。

  尼可地尔(Nicorandil)是一种ATP-K离子通道开放剂,具有选择性的开放ATP敏感钾离子通道的功能,在心脏保存液中加入尼可地尔有可能提高心脏保存液的保存效果。本实验的目的是在离体鼠心Langendorff灌注模型上,检验在器官保存液HTK液和UW液中加入钾离子通道开放剂尼可地尔对心脏保存效果的影响。

  1  材料与方法 

  1.1 实验动物和分组                            

  选用Wistar大白鼠32只,雌雄各半,体重300~400g,由北京阜外心血管病医院实验动物科提供。随机分为四组:UW液(U)组、HTK液(H)组、UW液+Nicorandil 组(U+N)、HTK液+Nicorandil(H+N) 组,每组8只。

  1.2 实验方法                            

  实验模型的建立、离体鼠心的切取、灌注和低温保存:

  大白鼠称体重后,腹腔注射戊巴比妥钠(65mg/kg)麻醉,仰卧固定于实验台上,游离出股静脉,经股静脉内注射肝素(3mg/kg)抗凝。迅速开胸,在主动脉和右锁骨下动脉交界处切断肺动、静脉,取出心脏,立即放入0~4℃ K-H缓冲液中,冲洗掉残留在主动脉内的血液。主动脉插管后,迅速移至Langendorff灌注模型灌注针上,用K-H缓冲液持续灌注,灌注压为75cmH2O,整个灌注期间用95%O2和5%CO2混合气体平衡,温度维持在37℃。肺动脉根部切开,使冠状动脉回流液引流充分。从开胸取心至灌注开始要在50~70s内完成,超过70s应放弃实验。灌注3min后,切开左心耳,经左心房、二尖瓣内,将连接有测压导管的心室球囊送入左心室,导管用生理盐水充满,勿存留气体,另一端连接多导生理记录仪。往心室球囊内缓慢注射适量生理盐水(40~60μl),使左心室舒张末压为10mmHg。15min后,心脏搏动可达到稳定状态,测定血流动力学基础值,包括左室收缩末压(LVESP)、左室舒张末压(LVEDP)、左室发展压(LVDP)、左室压力微分(±dp/dt)和冠脉流量。

  降低灌注温度至30℃以下后,经主动脉根部分别灌注4℃的四组心脏保存液,根据冠脉流量调节灌注速度,灌注压为75cmH2O。心脏停跳后,每只心脏在四种心脏保存液中分别低温(0~4℃)浸泡保存6h。

  6h后,复温至37℃,重新开始心脏灌注。15~20min以后,心脏搏动达到稳定状态,每隔10min测定一次血流动力学值和冠脉流出量,连续测定6次。复灌后35min,留取冠脉流出液2ml,置于-20℃冰箱中保存,以测定心肌酶漏出量。心脏灌注完成后,于左心室上取一块心肌(重量大于200mg),每次位置尽可能一致,置于液氮罐中保存,以备测定心肌ATP和CP含量。另取一块心肌组织,称湿重后放入100℃的烘箱中烘烤24h,再次称干重,计算心肌含水量。心肌含水量 =[(湿重-干重)/ 湿重]×100%。每组中随机选取一个心脏,留取标本,用3%戊二醛溶液固定后,置于4℃冰箱中保存,以备电子显微镜检查。

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