摘要： 目的探討不同劑量烏司他丁(UTI)對膿毒癥休克大鼠心功能及心肌絲裂原激活的蛋白激酶p38(p38MAPK)磷酸化的影響。方法 40只雄性SD大鼠隨機(jī)分5組:對照組(A組)、假手術(shù)組(B組)、膿毒癥組(C組),小劑量UTI組(D組)和大劑量UTI組(E組),8只/組。盲腸結(jié)扎穿刺術(shù)復(fù)制膿毒癥模型,24h后行心臟彩超檢測各組大鼠左室射血分?jǐn)?shù)(EF)及短軸縮短率(FS),并分離左心室心肌,免疫印跡法檢測p-p38MAPK、p38 MAPK表達(dá)。結(jié)果造模24 h后,A、B、C、D和E組大鼠左室EF值(%)分別為77.13±3.76,76.88±3.64,56.13±4.16,55.00±3.12,66.50±3.46,FS(%)分別為43.50±3.70,44.00±3.38,28.13±1.81,26.13±2.70,38.00±2.07。與B組相比,C、D和E組的EF和FS均顯著降低(P=0.000,0.000和0.002),但E組下降程度顯著低于C和D組(P=0.000和0.000),D組與C組無顯著性差異(P=0.541和0.166);各組大鼠心肌P-p38/p38MAK相對表達(dá)率比值分別為0.34±0.15,0.28±0.15,0.79±0.12,0.75±0.12,0.29±0.07。與B組比較,C組、D組p-p38/p38MAPK比值明顯升高(P=0.001),C組與D組升高程度無顯著性差異(P=0.682),E組較C組顯著下降(P=0.001),與B組比無顯著差異(P=0.972)。結(jié)論大劑量UTI對膿毒癥休克大鼠心功能具有保護(hù)作用,可能與抑制心肌p38MAPK磷酸化有關(guān)。 Objective To investigate the effect of different doses of ulinastatin(UTI) on the cardiac function and myocardial expression of p38 mitogen-activated protein kinase(p38MAPK) in septic rats.Methods Forty male SD rats were randomized equally into 5 groups,namely the control group(group A),sham-operated group(group B),sepsis group(group C),low-dose UTI group(group D),and high-dose UTI group(group E).Rat models of sepsis were established by cecal ligation and puncture(CLP),At 24 h after successful modeling,the left ventricle ejection fraction(LVEF) and fractional shortening(LVFS) were evaluated,and the myocardium of the left ventricle was sampled to examine the expression of the expressions of p38MAPK and p-p38MAPK using Western blotting.Results In groups A,B,C,D,and E,the LVEF was(77.13±3.76)%,(76.88±3.64)%,(56.13±4.16)%,(55.00+3.12)%,and(66.50±3.46)%,and the LVFS was(43.50±3.70)%,(44.00±3.38)%,(28.13+1.81)%,(26.13±2.70)%,and(38.00±2.07)%,respectively.Compared with group B at 24 h after CLP,LVEF and LVFS were markedly lowered in the groups C,D and E(P=0.000,0.000 and 0.002),but showed no significant differences between groups C and D(P=0.541 and 0.166);LVEF and LVFS were significantly lower in group E than in groups C and D(P=0.000 and 0.000).The p-p38/p38 ratio was similar between groups C and D(0.79±0.12 vs 0.75±0.12,P=0.682),but both significantly higher than that in group B(0.28±0.15,P=0.001);the ratio in group E was significantly lower than that in group C(P=0.001),but similar with that in group B(P= 0.972).Conclusion High-dose UTI can inhibit p38 phosphorylation,which may be the mechanism for its effect of myocardial protection in septic rat.
APP 