单磷酰脂A预处理对老年大鼠心脏的延迟保护作用及其机制探讨

The myocardial protection and mechanism of monophosphoryl lipid A on aged rat heart

目的探讨老年大鼠心脏药物预处理现象及其保护机制。方法在老年大鼠离体灌注心脏缺血再灌注（Ｉ／Ｒ）模型（Ｉ／Ｒ组）上，观察单磷酰脂Ａ（ＭＬＡ）预处理（ＭＬＡ组）对心脏Ｉ／Ｒ损伤的影响及其对丝裂素活化蛋白激酶（ＭＡＰＫ）活性和金属硫蛋白（ＭＴ）含量的影响。结果ＭＬＡ组明显减轻离体心脏的Ｉ／Ｒ损伤，其冠状动脉流出液中乳酸脱氢酶（ＬＤＨ）活性为（１４１±１５）Ｕ／Ｌ，肌红蛋白（Ｍｂ）含量为（５．３±１．９）ｍｇ／Ｌ，较Ｉ／Ｒ组〔分别为（２４９±２２）Ｕ／Ｌ及（９．８±１．７）ｍｇ／Ｌ〕均明显减少；心肌组织ＡＴＰ含量〔（３．５±０．５）ｍｍｏｌ／ｇ干重组织〕明显高于Ｉ／Ｒ组〔（２．２±０．４）ｍｍｏｌ／ｇ干重组织〕。组织湿、干重比值在ＭＬＡ组及Ｉ／Ｒ组分别为４．５±０．３和５．７±０．４（Ｐ＜０．０１）；组织总钙含量分别为（３．８±０．２）和（５．１±０．５）μｍｏｌ／ｇ干重组织；ＭＬＡ预处理后即刻ＭＡＰＫ被激活，１２小时达高峰〔（３．７±１．６）×１０４ｃｐｍ／ｍｇｐｒ〕，Ｉ／Ｒ组为（１．９±０．７）×１０４ｃｐｍ／ｍｇｐｒ，此时心肌组织ＭＴ含量较对照组明显升高〔分别为（３８．７±５．１）及（２３．３±２．５）μｇ／?

Objective To investigate the cardioprotective effects and mechanism of pharmacological preconditioning (PC) on aged rat heart. Methods In a model of isolated perfused heart of aged rat, the effects of monophosphoryl lipid A (MLA) on ischemic/reperfusion(I/R) injury, mitogen activated protein kinase (MAPK) activity, and metallothionein (MT) content were observed. Results MLA PC lowered the leakage of LDH (141±15) U/L vs (249±22) U/L in I/R group and Mb (5 3±1 9) mg/L vs.(9 8±1 7) mg/L in I/R group from the cardiomyocytes, attenuated the ATP depletion (3 5±0 5) vs (2 2±0 4) mmol/g d w in I/R group . MAPK was activated immediately after MLA administration and reached peak at 12 hours (3 7±1 6)×10 4 cpm/mg pr vs (1 9±0 7)×10 4 cpm/mg pr in I/R group . Meantime the MT content began to increase (38 7±5 1) vs (23 3±2 5) μg/g d w in I/R group and kept at high level till 24 hours. Conclusions MLA PC can protect the aged rat heart from I/R injury, and the protective mechanism is associated with MAPK mediated MT synthesis.