【作者】 王艳红；

【导师】 马平；

【作者基本信息】 山西医科大学 ， 麻醉学， 2006， 硕士

【摘要】 目的:观察糖尿病大鼠肢体缺血再灌注前后心肌组织中肿瘤坏死因子-α和核转录因子-κB表达的变化及全麻药丙泊酚对其的干预效应,探讨细胞因子、核转录因子在正常大鼠及糖尿病大鼠肢体缺血再灌注后心肌组织损伤中的作用机制及丙泊酚的保护作用机制。方法:采用220-250g健康成年雄性SD大鼠,分为正常大鼠和糖尿病大鼠两系列,用链脲佐菌素(STZ)诱发大鼠糖尿病。正常大鼠随机分为:①对照组(IA组, n=8),②肢体缺血再灌注组(ⅠB组, n=8),③肢体缺血再灌注+丙泊酚组(ⅠC组, n=8);糖尿病大鼠分为①对照组(ⅡA组, n=8),②肢体缺血再灌注组(ⅡB组,n=8),③丙泊酚组(ⅡC组, n=8),④肢体缺血再灌注+丙泊酚组(ⅡD组, n=8)。采用免疫组织化学法对TNF-α和NF-κB进行定性、半定量检测。用放射免疫法对TNF-α进行定量检测。结果:(1)非糖尿病大鼠肢体缺血再灌注(ⅠB组)后可致心肌损伤,组织中NF-κB和TNF-α表达升高与对照组(非糖尿病大鼠,ⅠA组)比较差异有显著性(P<0.05)。(2)糖尿病大鼠(ⅡA组)心肌组织NF-κB和TNF-α表达升高,与非糖尿病大鼠(ⅠA组)组比较差异有显著性(P<0.05)。(3)糖尿病大鼠肢体缺血再灌注大鼠心肌组织NF-κB和TNF-α表达显著升高。糖尿病大鼠肢体缺血再灌注组(ⅡB组)的阳性表达最显著与非糖尿病大鼠组(ⅠA组)、非糖尿病大鼠肢体缺血再灌注组(ⅠB组)、糖尿病大鼠组(ⅡA组)比较差异均有显著性(P<0.05)。(4)丙泊酚干预后各组NF-κB和TNF-α表达均减少。药物干预前后各组,即非糖尿病大鼠肢体缺血再灌注(ⅠB组)与非糖尿病大鼠肢体缺血再灌注+丙泊酚(ⅠC组)、糖尿病大鼠(ⅡA组)与糖尿病大鼠+丙泊酚(ⅡC组)、糖尿病大鼠肢体缺血再灌注组(ⅡB组)与糖尿病大鼠肢体缺血再灌注+丙泊酚(ⅡD组)两两比较均差别有显著性(P<0.05)。(5)其余各组两两比较差别无显著性(P>0.05)。结论:(1)糖尿病大鼠组、糖尿病大鼠肢体缺血再灌注组和非糖尿病大鼠肢体缺血再灌注组大鼠心肌组织的NF-κB和TNF-α表达均升高,且糖尿病大鼠肢体缺血再灌注组大鼠表达最显著。(2)丙泊酚能降低非糖尿病大鼠肢体缺血再灌注组、糖尿病大鼠组、糖尿病大鼠肢体缺血再灌注组大鼠心肌组织NF-κB和TNF-α的表达,具有抗炎、抗氧化作用,对糖尿病、肢体缺血再灌注诱发心肌组织损害有保护作用。更多还原

【Abstract】 Objective To investigate the mechanism of action of cytokine and nuclear factor in normal rats and diabetes mellitus rats following limbs ischemic reperfusion and the mechanism of protect action of Propofol, the experiment was made on the changes of nuclear factor of kappa B ( NF-κB) and tumor nerosis factor-α(TNF-α)in diabetes mellitus rat’s myocardium following limbs ischemic reperfusion and the effect of Propofol in the process.Method Adult male Ssprague-Dawley rats, weighing 220-250g were randomized assigned to normal rats and diabetes mellitus rats. The rats were induced diabetes mellitus with streptozotocin (STZ).The normal rats were divided into three groups at random: group IA(n=8) control group,ⅠB(n=8) limbs ischemic reperfusion group , groupⅠC(n=8) limbs ischemic reperfusion and Propofol group. Diabetes mellitus rats were divided into four group at random: groupⅡA(n=8) control group, groupⅡB(n=8) limbs ischemic reperfusion group, groupⅡC(n=8) Propofol group, groupⅡD(n=8) limbs ischemic reperfusion and Propofol group.the exprement deployed immunohistochemistry(IHC) in order to detect qualitatively and semiquantitatively the express of TNF-αand NF-κB.and radio-immunity(RI) in order to detect quantitative the level of TNF-α.Result First,limbs ischemic reperfusion(group IB)can cause myocardial damage.compared with normal rat( group IA), the level of NF-κB and TNF-αis increase and there is statistical significance (P<0.05). Second, diabetes mellitus rats(groupⅡA)can cause myocardial damage.compared with normal rat( group IA), the level of NF-κB and TNF-αis increase and there is statistical significance (P<0.05). Third, diabetes mellitus with limbs ischemic reperfusion can cause myocardial significant damage, compared with normal rat(group IA ) and limbs ischemic reperfusion(groupⅠB)and diabetes mellitus rats(groupⅡA),the level of NF-κB and TNF-αis predominance heighten. and there is statistical significance (P<0.05). Fourth, compared with theAP:PA of intervention of Propofol ,every group level of NF-κB and TNF-αis cut down after intervention of Propofol and there are statistical significance (P<0.05). Fifth,the rest is not significant difference each other (P>0.05).Conclusion First, the level of NF-κB and TNF-αwas step up for diabetes mellitus rat and limbs ischemic reperfusion rat with diabetes mellitus and limbs ischemic reperfusion rat without diabetes mellitus. Moreover, the level is maxlmum for diabetes mellitus with limbs ischemic reperfusion rat. Second, Propofol can cut down the level of NF-κB and TNF-αfor diabetes更多还原