Inhibition of calcineurin is involved in cardioprotection induced by ischemic postconditioning in rats
- VernacularTitle:钙调神经磷酸酶的抑制参与大鼠心脏缺血后处理的保护作用
- Author:
Shutong YAO
;
Xiuhua LIU
;
Xiumei ZHAO
;
Fei RONG
- Publication Type:Journal Article
- Keywords:
Ischemic postconditioning;
Reperfusion;
Calcineurin;
Calreticulin
- From:Chinese Journal of Pathophysiology
2000;0(12):-
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To demonstrate the mechanisms underlying cardioprotection induced by ischemic postconditioning(I-postC) via studying the alteration of calreticulin(CRT)/calcineurin(CaN) signaling pathway in rat heart subjected to ischemia/reperfusion(I/R).METHODS: The model of myocardial I/R injury in vivo was made by occluding the left anterior descending artery for 45 min followed by 24 h of reperfusion in Wistar rats.Hemodynamics and activity of lactate dehydrogenase(LDH) and creatine kinase-MB(CK-MB) in plasma were measured.Myocardial infarct size was measured by 2,3,5-triphenyltetrazolium chloride(TTC) staining and cardiomyocyte apoptosis was detected using in situ TDT-mediated dUTP nick end labeling(TUNEL).The activity of CaN,the expressions of CaN and CRT in myocardium were detected by enzyme reaction phosphorus measurement and Western blotting analysis,respectively.RESULTS: Cyclosporin A,the inhibitor of CaN,limited significantly myocardial infarct size and cardiomyocyte apoptosis induced by I/R,but had no significant effect on cardiac function.I-postC ameliorated significantly the cardiac dysfunction induced by I/R.Compared with those in I/R group,the myocardial infarct size,the LDH and CK-MB activities in plasma and the cardiomyocyte apoptotic index were significantly reduced in I-postC group.In addition,I/R-induced upregulation of CaN activity,CaN and CRT expression were relieved by I-postC.No significant difference was found between I-postC and ischemic preconditioning groups.I-postC had stronger protective effect on the reperfused heart compared with cyclosporin A.CONCLUSION: The findings indicate that I-postC protects myocardium against I/R injury,at least in part,via inhibiting the CRT/CaN signaling pathway.
