摘要
目的探讨单磷酰脂 A(MLA)预处理对大鼠缺血再灌注心肌的影响及环氧化酶-2(COX-2)表达的作用。方法雄性 Wistar 大鼠24只分为4组:健康对照组(NC 组)、单纯缺血再灌注组(I/R 组)、单磷酰脂 A 预处理组(MLA-DP组)、单磷酰脂 A 预处理与 COX-2抑制剂 NS-398组(MLA+NS-398组);检测各组心功能、心肌梗死的范围;测定 MLA 预处理后24 h COX-2蛋白表达及心肌中前列腺素类化合物的含量。结果与 NC 组比较,MLA-DP 组心功能明显改善[左室内压峰值(LVSP)分别为:(124.1±12.0)mm Hg和(112.0±26.3)mm Hg,P<0.01],与 MLA-DP 组比较,MLA+NS-398组心功能下降(P<0.01)、心肌梗死范围增大[分别为(14±3)%和(32±9)%,P<0.01]。与 NC 组比较,MLA-DP 组 COX-2蛋白水平明显增加(P<0.01),心肌中前列腺素类化合物含量明显增加(P<0.01)。同 MLA-DP 组比较,MLA+NS 398组蛋白水平无明显变化,但MLA+NS-398组前列腺素类化合物含量明显减少(P<0.01)。结论 MLA 预处理适度上调了心肌细胞 COX-2蛋白表达,增加心肌前列腺素类化合物前列腺素 E_2的量,从而对大鼠缺血再灌注心肌有延迟保护作用。
Objective To determine whether monophosphoryl lipid A （MLA） could precondition rat heart and induce a cardioprotection by a mechanism involving the cyclooxygenase-2 （COX-2） activation. Methods Wistar rats were divided into four groups： （1） control group（NC group） ; （2） I/R group： the hearts were injected with vehicle, and 24 h later, the animals＇ hearts were subjected to a 30-min left coronary artery occlusion followed by a 120 min reperfusion（I/R） ; （3） MLA-P group： the hearts were injected with MLA （450 g/kg, iv）, then the following steps similar to （2）; （4） MLA-kNS-398 group： the hearts were injected with MLA, 35 min before I/R , the hearts were injected with NS-398, a selective COX-2 inhibitor, then similar to （2）. At the end of reperfusion, the myocardial contractile function and the myocardial infarct size were detected. The myocardial COX-2 protein expression after 24 h of treatment, the myocardial content of prostaglandin（PG）E2 and 6-keto-PGF1. were detected after 24 h of treatment. Results Compared with NC group,the MLA-P group had the improved myocardial contractile function（LVSP, ±dp/dt max）（P〈0.01 ）, the reduced infarct size （P〈 0.01 ）, the elevated expression of COX-2 protein （P〈 0.01 ）, increased myocardial content of PGs（P〈0.01）. Compared with MLA-P group,the MLA＋NS-398 group had the decreased myocardial contractile function （LVSP.±dp/dt max）（P〈0. 01）, the increased infarct size（P〈0. 01 ）, not changed expression of COX-2 protein（P〉0.05）, decreased myocardial content of PGs（P〈0. 01）. Conclusions Monophosphoryl lipid A preconditioning can protect the heart. The up-regulation of COX-2 plays an essential role in the cardioprotection afforded by monophosphoryl lipid A preconditioning against myocardial ischaemic reperfusion.
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2006年第2期137-140,共4页
Chinese Journal of Geriatrics
基金
湖北省教育厅2004年科研基金资助优秀中青年项目(2004Q002)
关键词
氧化还原酶类
缺血预处理
心肌
心肌再灌注损伤
Oxidoreductases
Ischemic preconditioning, myocardial
Myocardial reperfusion injury
