蛋白激酶C和蛋白酪氨酸激酶活性对缺血再灌注心肌细胞凋亡影响的实验研究

Experimental study on effect of PKC and protein tyrosine kinase on cardiomyocyte apoptosis during ischemia/reperfusion in rat heart

为探讨缺血预适应（Ｉｓｃｈｅｍｉｃ Ｐｒｅｃｏｎｄｉｔｉｏｎｉｎｇ，ＩＰ）早期以及蛋白激酶Ｃ（Ｐｒｏｔｅｉｎ ｋｉｎａｓｅ Ｃ，ＰＫＣ）及蛋白酪氨酸激酶（Ｐｒｏｔｅｉｎ Ｔｙｒｏｓｉｎｅ Ｋｉｎａｓｅ，ＰＴＫ）激动剂和抑制剂对缺血再灌注（Ｉ／Ｒ）心肌细胞凋亡的影响以及ＩＰ效能发挥通路中ＰＫＣ和ＰＴＫ的关系。用ＴＵＮＥＬ法检测Ｉ／Ｒ心肌细胞凋亡。结果显示：１、ＩＰ早期能显著降低Ｉ／Ｒ心肌细胞凋亡（Ｐ＜０．０１）；２、ＰＫＣ激动剂ＰＭＡ及ＰＴＫ激动剂ａｎｉｓｏｍｙｃｉｎ均能显著降低Ｉ／Ｒ心肌细胞凋亡（Ｐ＜０．０１）；３、ＰＫＣ抑制剂灯盏花素不能阻断ａｎｉｓｏｍｙｃｉｎ降低Ｉ／Ｒ心肌细胞凋亡的作用，而ＰＴＫ抑制剂ｌａｖｅｎｄｕｓｔｉｎ Ａ则能阻断ＰＭＡ的效应。上述研究显示：ＰＭＡ和ａｎｉｓｏｎｙｃｉｎ能模拟ＩＰ早期的抗Ｉ／Ｒ心肌细胞凋亡的作用；并提示在ＩＰ信息传递通路中ＰＴＫ位于ＰＫＣ的下游。

The purpose of this study was to use the TUNEL method for datecting I/R cardiomyocyte apoptosis to investigate the effect of ischemic preconditioning(IP),the activators of protein kinase C(PKC) and protein tyrosine kinase(PTK) on ischemia/reperfusion(I/R) cardiomyocyte apoptosis,and the relationship betWeen PKC and PTK for IPs anti-apoptosis effect in rat hearts.The results showed that:(1)IP could reduce MR cardiomyocyte apoptosis significantly (P<0.01);(2)PMA,the activator of PKC,and anisomycin,the activator of PTK,could also reduce I/R anisomycins anti-apoptosis during MR,and lavendustin A,the inhibitor of PTK,could block the effect of PMAs anti -apoptosis during I/R.These data suggest both PMA and anisomycin could mimic IPs anti-apoptosis effect during I/ R;PTK seems to be downstream of PKC for IPs anti-apoptosis effect during im injury in rat hearts.