摘要
本工作在大鼠盲肠结扎加穿孔（ＣＬＰ）腹膜炎败血症休克模型上观察休克不同阶段心肌肌浆网（ＳＲ）钙摄取功能的变化，并探讨了其变化机制。结果显示：败血症休克早期，心肌ＳＲ摄钙初速率降低，但ＳＲ最大摄钙量及Ｃａ２＋－ＡＴＰａｓｅ活性没有明显变化；败血症休克晚期，心肌ＳＲ摄钙初速率、最大摄钙量以及Ｃａ２＋－ＡＴＰａｓｅ活性显著降低。测定Ｃａ２＋，Ｍｇ２＋和ＡＴＰ对早、晚期休克大鼠心肌ＳＲ钙泵的亲和力以及对ＳＲ钙摄取率刺激作用的Ａ０．５值均无显著变化，而向ＳＲ钙摄取反应体系中分别加入蛋白激酶Ａ的催化亚基，钙调素以及蛋白激酶Ｃ的活性片段，对早、晚期休克大鼠心肌ＳＲ钙摄取率应有的增强效应发生减弱或消失。结果表明，随着休克进展，心肌ＳＲ钙摄取功能损伤加重，其原因可能主要与心肌ＳＲ蛋白磷酸化反应减弱有关，而非Ｃａ２＋，Ｍｇ２＋，和ＡＴＰ对ＳＲ钙泵的调节水平改变所致。
The underlying mechanism of Ca2+ uptake function of cardiac sarcoplasmic reticulum (SR) was investigsted in the rat septic shock model produced by cecal ligstion and puncture (CLP). The results are as follows. During the early phase of sepsis, the initial rate of ATP-dependent Ca2+ uptake by SR was decreased, while both the capacity of Ca2+ uptake and the activity of Ca2+-ATPase were unaffected. In the late sepsis, the impairment in SR function was even greater as the initial rate and the capacity of Ca2+uptake by SR were significantly decreased, and this was paralleled by a reduction in Ca2+-ATPase activity. Although Ca2+ affinity (Km value) to calcium pump and the A0. 5 values for Mg2+ and ATP activation on the Ca2+ uptake rate were unchanged, during sepsis the phosphorylation of SR vesicles by adding of catalytic subunit of the cAMP-depentent protein kinase (PKA), calmodulin, or the fragment of PKC into Ca2+ uptake buffer, failed to stimulate Ca2+ uptake activities of SR isolated from early or late septic rats. These data suggest that depression of cardiac SR function is asoavated as sepsis develops, the impairment of SR Ca2+ uptake is possibly based on a mechanism of defective phosphorylation of SR rather than the ionic and energic regulatory actions of Ca2+, Mg2+, ATP on cardiac SR.
出处
《生理学报》
CAS
CSCD
北大核心
1995年第4期336-342,共7页
Acta Physiologica Sinica
基金
国家自然科学基金
关键词
败血症
休克
心肌
肌浆网
钙摄取
septic shock
sarcoplasmic reticulum
ca2+ uptake, protein phosphorlation
