白细胞介素-2预处理对缺氧/复氧心肌细胞收缩功能的影响

Interleukin-2 pretreatment improves the contractility of isolated rat ventricular myocytes during hypoxia and reoxygenation

目的 :观察白细胞介素 - 2 (IL - 2 )预处理对缺氧 /复氧过程中心肌细胞收缩功能的作用并探讨其作用机制。方法 :采用酶解法分离成年大鼠心室肌细胞缺氧 /复氧模型 ,用视频跟踪计算机系统记录测定单个心室肌细胞收缩。心室肌细胞收缩参数包括最大收缩幅度 (dL)、细胞最大收缩速度 (+dL/dtmax)、细胞最大舒张速度(-dL/dtmax)和舒张末期细胞长度。结果 :①缺氧 /复氧过程中 ,缺氧 5、10、15和 2 0min时 ,心肌细胞dL、+dL/dtmax和 -dL/dtmax明显降低。复氧 5min时±dL/dtmax和dL有所恢复 ,但复氧 10min后±dL/dtmax、dL和舒张末期细胞长度又明显降低。② 2× 10 3 U/LIL - 2对心室肌细胞收缩无明显作用。用此浓度IL - 2预处理心室肌细胞 15min可明显改善缺氧 /复氧引起的心室肌细胞收缩功能的减弱。③用选择性κ -阿片受体拮抗剂nor-BNI(10 -8mol/L)预处理后 ,IL - 2对缺氧 /复氧过程中心室肌细胞收缩的影响被减弱。④PKC抑制剂chelerythrine(3× 10 -6mol/L)可明显减弱IL - 2的作用。⑤IL - 2对缺氧 /复氧过程中心室肌细胞收缩的影响可被线粒体ATP敏感性钾通道阻断剂 5 -HD(10 -4mol/L)明显抑制。结论 :2× 10 3 U/LIL - 2预处理可明显改善缺氧 /复氧心室肌细胞的收缩功能。其作用是由κ

AIM: To investigate the effect and possible mechanisms of interleukin-2 (IL-2) on the cell contractility in cardiomyocytes during hypoxia and reoxygenation.METHODS: Glucose-free Krebs-Henseleit (K-H) solution, gassed with 95% N 2 and 5% CO 2 for hypoxia, were used. The cell contractility were determined after 20 min of hypoxia and 30 min of reoxygenation by the video tracking system. The parameters of cell contractility included peak velocity of cell shortening (+d L /d t max), peak velocity of cell relengthening (-d L /d t max), contraction amplitude (dL) and end-diastolic cell length.RESULTS: It was shown that during hypoxia, the cell contraction was depressed. All the parameters were unable to return to the pre-hypoxia level during reoxygenation. Pretreatment with IL-2 at 2×10 3 U/L attenuated the inhibitory effect of hypoxia/reoxygenation on contractility in single ventricular myocytes. The effect of IL-2 was reduced in the presence of 10 -8 mol/L nor-binaltorphimine (nor-BNI), a selective κ-opioid receptor antagonist. On blockade of protein kinase C with 3×10 -6 mol/L chelerythrine, the effect of IL-2 was significantly attenuated. The effect of IL-2 was also blocked by 10 -4 mol/L 5-hydroxydecanoate (5-HD), a mitochondrial ATP-sensitive potassium (K ATP ) channel blocker. CONCLUSIONS: The results of the present study provide evidence that pretreatment with IL-2 at 2×10 3 U/L attenuates the effect of hypoxia/reoxygenation on cell contraction in the isolated ventricular myocytes. The κ-opioid receptor mediates the effect of IL-2, in which activation of PKC and opening of mitochondrial ATP-sensitive potassium (mito K ATP ) channel are involved.