[金属硫蛋白参与心肌或培养心肌细胞缺血或缺氧预处理后的延迟保护作用]

[Metallothionein involvement in the delayed protection after ischemic or anoxic preconditioning in myocardium or cultured cardiomyocytes].

作者信息

Chen K, Zhang J, Ye C

机构信息

First Hospital, Beijing Medical University.

出版信息

Zhonghua Yi Xue Za Zhi. 1997 Feb;77(2):106-10.

PMID:9596940

Abstract

OBJECTIVE

To study whether metallothionein (MT) is an OH scavenger and plays a protective role in cardiac ischemic/reperfusion injury. MT involves in the delayed protection 24 hr after preconditioning (PC).

METHODS

MT contents in myocardium or cultured cardiomyocytes are assayed at the 0 hr, 12 hr, and 24 hr after PC on the model of rabbit heart in situ or that of the cultured cardiomyocytes. The myocardial infarct size, LDH release, cell viability, and the content of cellular MDA were measured with or without the intervention of PD098059, the inhibitor of mitogen-activated protein kinase in the models before PC and different time intervals after PC.

RESULTS

The MT contents were increased significantly at 2 hr (1406.2 +/- 112.2 vs 129.9 +/- 10.4 pmol/mg Pr., P < 0.01, in cardiomyocytes) and 24 hr (1032.7 +/- 199.1 vs 129.9 +/- 10.4 pmol/mg Pr., P < 0.01, in cardiomyocytes; 62.1 +/- 12.6 vs 27.2 +/- 3.7 pmol/mg Pr., P < 0.01, in myocardium) after PC compared with those in normal group. The infarct sizes (13.2 +/- 3.6% vs 32.3 +/- 5.7%, P < 0.05) and the rise of LDH release in plasma (1944 +/- 256 vs 2826 +/- 239 IU/L, P < 0.05) were greatly decreased in preconditioned myocardium after a long time ischemia-reperfusion than those in the unpreconditioned. Compared with the cardiomyocytes unconditioned, the number of viable cell (71.0 +/- 1.6 vs 48.2 +/- 2.2%, P < 0.01) was greatly increased, the cellular MDA contents (33.5 +/- 12.8 vs 103.5 +/- 15.0 nmol/mg Pr., P < 0.01) and the LDH release (850.0 +/- 139.1 vs 1552.0 +/- 102.6 IU/L, P < 0.01) were dramatically decreased in preconditioned ones. All the delayed protection at 24 hr after PC were completely disappeared with the inhibition of MT's production with PD098059 (P > 0.05).

CONCLUSION

The myocardium or cardiomyocytes at 24 hr after PC are offered more capacity to tolerate the I/R damage, and MT involves in the delayed protection.

摘要

目的

研究金属硫蛋白（MT）是否作为羟基清除剂在心脏缺血/再灌注损伤中发挥保护作用。MT参与预处理（PC）24小时后的延迟保护作用。

方法

采用兔原位心脏模型或培养心肌细胞模型，在PC后0小时、12小时和24小时测定心肌或培养心肌细胞中的MT含量。在PC前及PC后不同时间间隔，使用丝裂原活化蛋白激酶抑制剂PD098059干预模型，测量心肌梗死面积、乳酸脱氢酶（LDH）释放、细胞活力及细胞丙二醛（MDA）含量。

结果

与正常组相比，PC后2小时（心肌细胞中：1406.2±112.2对129.9±10.4 pmol/mg Pr.，P<0.01）和24小时（心肌细胞中：1032.7±199.1对129.9±10.4 pmol/mg Pr.，P<0.01；心肌中：62.1±12.6对27.2±3.7 pmol/mg Pr.，P<0.01）心肌MT含量显著增加。长时间缺血再灌注后，预处理心肌的梗死面积（13.2±3.6%对32.3±5.7%，P<0.05）和血浆LDH释放增加量（1944±256对2826±239 IU/L，P<0.05）较未预处理心肌明显降低。与未预处理的心肌细胞相比，预处理心肌细胞的存活细胞数量显著增加（71.0±1.6对48.2±2.2%，P<0.01），细胞MDA含量（33.5±12.8对103.5±15.0 nmol/mg Pr.，P<0.01）和LDH释放（850.0±139.1对1552.0±102.6 IU/L，P<0.01）显著降低。用PD098059抑制MT生成后，PC后24小时的所有延迟保护作用完全消失（P>0.05）。