尾加压素预处理对大鼠心脏缺血再灌注损伤的影响

Effects of human urotensin II on ischemia/reperfusion injury in isolated perfused rat hearts

目的 :探讨尾加压素 (UII)预处理对于离体灌流大鼠心脏缺血再灌注 (I/R)损伤的影响。方法 :在离体灌流的SD大鼠心脏I/R模型上 ,以UII预灌注心脏 ,采用MFLLab2 0 0心功能软件监测心功能 ,以试剂盒测定心肌细胞ATP、总钙、丙二醛含量和乳酸脱氢酶 (LDH)漏出 ,并观察其对于冠脉流出量 (CPF)的影响。结果 :UII预处理组与单纯I/R组比较 ,冠脉流出液中LDH低 2 8% [(78 3± 18 1)U/Lvs (10 9 3± 2 3 9)U/L ,P <0 0 5 ],心肌组织MDA和钙含量分别低 2 4 %和 2 7% (P <0 0 5 ) ;ATP含量高 73% (P <0 0 5 )。与I/R组比较 ,UII预处理组CPF高 4 2 % [(5 4± 0 7)mL/minvs (3 8± 0 8)mL/min ,P <0 0 5 ],LVEDP低 2 0 % (P <0 0 5 ) ,±dp/dtmax分别高 2 5 %和 4 5 % (P <0 0 5 ) ;冠脉流出液中NO-2 /NO-3 含量高 6 3% (P <0 0 5 )。结论 :UII预处理可以减轻离体灌注大鼠心脏I/R所造成的损伤 ,其机制与NO介导的冠脉扩张效应有关。

AIM: To investigate the effects of human urotensin II (hUII) on ischemia/reperfusion (I/R) injury in isolated rat hearts. METHODS: In the ischemia/reperfusion (I/R) model of isolated perfused rat hearts,the effects of hUII pretreatment on cardiac function was monitored with cardiac function software of MFL Lab200. ATP,total calcium,and malondialdehyde (MDA) content in myocardium were detected. The coronary perfusion flow (CPF) and lactate dehydrogenase (LDH) activity in coronary effluent were measured during reperfusion. RESULTS: In the hUII pretreated group,the release of LDH from myocardium was lower [(78.3±18.1)U/L] than I/R group [(109.3±23.9) U/L,P< 0.05],with decreased contents of MDA and calcium in myocardium (decreased by 24% and 27%,respectively,P< 0.05) and an increased myocardial ATP content [(3.8±0.4)μmol/g dw vs (2.2±0.4)μmol/g dw,P< 0.05)]. At the same time,hUII pretreatment increased CPF [(5.4±0.7) mL/min vs (3.8±0.8) mL/min in I/R group,P< 0.05],reduced left ventricular end-diastolic pressure (LVEDP) by 20% ( P< 0.05) with increased±d p /d t max [(217±38) kPa/s and (119±18) kPa/s vs (173±29) kPa/s and (82±25) kPa/s in I/R groups,respectively,P< 0.05]. hUII pretreatment also increased natrite/natrate (NO -_2/NO -_3) content in coronary effluent [(52.2±12.0)μmol/L vs (32.1±10.2)μmol/L in I/R group,P< 0.05)]. CONCLUSION: hUII pretreatment attenuated I/R injury in isolated perfused rat hearts. The protective mechanism might be associated with NO-mediated coronary vasodilation.