二氮嗪预处理对糖尿病大鼠心肌保护作用减弱机制的初步研究  

Mechanism of weakening effect of diazoxide preconditioning on diabetic myocardium

作　　者：韩劲松[1] 韩宏光[1] 赵建传 王辉山[1] 尹宗涛[1] 

机构地区：[1]沈阳军区总医院心血管外科,沈阳110016 [2]沈阳军区政治部门诊部,沈阳110013

出　　处：《中国体外循环杂志》2012年第4期243-246,共4页Chinese Journal of Extracorporeal Circulation

摘　　要：目的探讨二氮嗪预处理(DPC)对糖尿病大鼠心肌保护作用减弱的机制。方法取糖尿病SD大鼠及非糖尿病SD大鼠48只,建立离体心脏Langendorff灌注模型,各分为4组(每组6只):对照组(CON组):全心灌流120 min。缺血再灌注组(I/R组):在心脏平衡灌流30 min后,缺血30 min再灌注KH液1 h。DPC组:在心脏平衡灌流10 min后,给予含二氮嗪(100μmol/L)的KH液灌注5 min,再复灌不含二氮嗪的KH液5 min后,再给予含二氮嗪的KH液灌注5 min,再复灌不含二氮嗪的KH液5 min,然后缺血30 min,再灌注KH液1 h。二甲基亚砜组(DMSO组):用DMSO代替二氮嗪,过程同DPC组。比较各组冠脉流出液中肌酸激酶(CK)、心肌组织丙二醛(MDA)、超氧化物岐化酶(SOD)、心肌组织一氧化氮(NO)、环磷酸鸟苷(cGMP)、一氧化氮合酶(NOS)的变化。结果①CK活性:非糖尿病大鼠中,再灌注后DPC组CK活性与I/R组比较明显降低(P<0.01),DMSO组与I/R组比较差异无统计学意义(P>0.05);而糖尿病大鼠中,再灌注后DPC组与I/R组比较,差异均无统计学意义(P>0.05)。②MDA、SOD含量:非糖尿病大鼠中,DPC组MDA含量明显低于I/R组(P<0.01)、SOD含量明显高于I/R组(P<0.01)。而在糖尿病大鼠中,DPC组与I/R组比较,MDA和SOD的含量差异无统计学意义(P>0.05)。③心肌组织NO、cGMP及NOS含量:非糖尿病大鼠中,DPC组NO、cGMP及NOS含量与I/R组比较明显增加(P<0.01),DMSO组与I/R组比较差异无统计学意义(P>0.05);而糖尿病大鼠中,DPC组与I/R组、DMSO组比较,差异无统计学意义(P>0.05)。结论 DPC对糖尿病大鼠心肌的保护作用减弱,其机制可能与糖尿病大鼠心肌NO-cGMP信号通路表达受抑制有关。Objective To explore the mechanism of weakening effect of diazoxide preconditioning （DPC） on diabetic myocar- dium in rats. Methods Twenty - four normal male Sprague - Dawley （SD） rats were divided into four groups, six of each ： non - dia- betic control group, non -diabetic I/R group, non -diabetic DPC group and dimethyl sulfoxide （DMSO） group; and twenty -four diabetic male rats were divided as diabetic control group, diabetic I/R group, diabetic DPC group and diabetic DMSO group. The Lange- ndorff isolated heart perfusion model was established. The control group had a 90 - min perfusion without any intervention. The I/R group group had a 30 -min equilibration period, a 30 -min ischemia, and a 30 -min reperfusion. The DPC group had a 10 -min e- quilibration, two cycles of 100 μM diazoxide perfusion, 5 rain each, followed by a 5 - min diazoxide - free period before the 30 rain is- ehemia and a 30 - min reperfusion. The DMSO group perfused with the same treatment as in the DPC group, except that diazoxide was replaced with natriichloridum and DMSO. The activity of creatine kinase （CK） in coronary outflow, contents of malonyldialdehyde （MDA） and super- oxide dismutase （SOD） in myocardium were detected. The changes of content of myocardial nitric oxide （NO）, guanosine monophosphate （cGMP） and nitric oxide synthase （NOS） were also assessed. Results In non -diabetic rats, the content of CK, MDA were significantly decreased in DPC group comparing with those in I/R group. Furthermore, in DPC group, the activity of SOD and the content of NO, cGMP and NOS were significantly increased comparing with those in I/R group （ P 〈 0.05 ）. By con- trast, there were no significant changes between IfR DPC group and I/R groups in diabetic rats （ P 〉 0.05）. Conclusion DPC have a weakening protective effect on diabetic rat heart, which may be related with inhibiting of the expression of the NO - cGMP signaling pathway.

关 键 词：二氮嗪 糖尿病 环磷酸鸟苷 一氧化氮 

分 类 号：R587.1[医药卫生—内分泌]