腺苷受体激动剂预处理对保存大鼠心脏的影响及其与NF-κB的关系

Effects of adenosine A1 receptor-induced delayed preconditioning on heart preservation and its relation with NF-κB

目的 探讨腺苷A1受体激动剂预处理延迟效应对低温St Thomas液保存大鼠心脏的影响及其与心肌核转录因子 κB(nuclearfactorkb ,NF κB)的关系。方法 Wistar大鼠随机分6组:A、C、D组以高选择性A1受体激动剂CCPA(2 chloro N6 cyclopen tyladenosine)预处理,其中D组在预处理前15min注射NF κB抑制剂(pyrrolidindiethyldithiocarbamate ,PDTC) ;B、E组仅注射生理盐水;F组注射PDTC后再注射生理盐水。2 4h后A、B组4℃St.Thomas液保存4h ,复灌1h ,而另4组低温缺血3h ,复灌1h。观测心功能、磷酸肌酸激酶同工酶(CK MB)、三磷酸腺苷(ATP)等。结果 A组左室内压上升与下降最大速率恢复率(±dp dtmax)为(62 83±17 2 7) %、(66 81±18 99) % ,心肌ATP含量(3 67±1 42 )×10 - 3μmol g ;而B组±dp dtmax分别为(4 0 41±18 2 9) %、(4 4 70±2 5 14 ) % ,ATP含量(1 46±0 5 4)×10 - 3μmol g ;A组明显高于B组,差异有显著性(P <0 0 1,P <0 0 5 )。C组±dp dtmax恢复率、ATP都明显高于D、E、F组(P <0 0 1,P <0 0 5 ) ,而D、E、F组间无明显差异。结论 以腺苷A1受体激动剂能诱导预处理的延迟效应,改善低温St .Thomas液保存离体大鼠心脏的保存效果,而该效应的信号传递与心肌核转录因子 κB的活化有关。

Objective To study the potential improvement of donor heart storage by A1 adenosine receptor-induced delayed preconditioning and its relation with NF-κB. Methods A total of 64 male Wistar rats were randomly divided into 6 groups. Group A was pretreated with 2-chloro-N6-cyclopen-tyladenosine (CCPA), and Group B was only injected saline. Twenty-four hours later, the hearts in groups A and B were stored in St.Thomas solution for 4 h at 4 ℃ and reperfused with K-H buffer for 1 h. Group C was administered with CCPA after 15-minute saline injection, and Group D was injected with inhibitor of nuclear factor κB, pyrrolidindiethyldithiocarbamate (PDTC) first and 15 min later injected with CCPA. Group E was only injected with saline and Group F with PDTC. Twenty-four hours later, the rat hearts were isolated, perfused with H-K buffer solution on the Langendorff apparatus, and subjected to hypothermic ischemia for 180 min with intermittent perfusion of modified St. Thomas solution, and reperfused with 37 ℃ H-K buffer for 60 min. Left ventricular function, myocardial CK-MB leakage, tissue levels of adenosine triphosphate were measured. Results The recovery rate of ±dp/dt max left ventricle in Group A were much higher than that of Group B, while that in Group C were much higher than that in groups D, E and F (P<0.05). Conclusion CCPA may trigger myocardial delayed preconditioning and has some beneficial effects on Wistar rat donor heart preserved in 4 ℃ with modified St.Thomas solution, in which NF-κB may play an essential role in the signaling.