Studies on the mechanism of beneficial effects of ATP-MgCl2 following hepatic ischemia.

Studies on the mechanism of beneficial effects of ATP-MgCl2 following hepatic ischemia.
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肝缺血后 ATP-MgCl2 有益作用机制的研究。

DOI:
10.1152/ajpregu.1983.244.5.r695
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发表时间:
1983
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
Chaudry,IH
Chaudry,IH
中科院分区:
--
文献类型:
--
作者:
Ohkawa,M;Clemens,MG;Chaudry,IH

文献摘要

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肝缺血后输注 ATP-MgCl2 可显着提高动物的存活率。为了确定输注 ATP-MgCl2 的亚细胞效应以及这种效应是否是通过血管舒张介导的,在大鼠中产生全肝缺血 90 分钟,然后再灌注。然后,大鼠静脉注射 0.5 ml 盐水、多巴胺、罂粟碱或 ATP-MgCl2。在回流后的不同时间间隔,分离肝线粒体。复流后 1 小时,ADP-O 比值和呼吸控制比 (RCR) 显着降低,并且复流后 3 小时,盐水处理大鼠的线粒体中这些参数进一步下降。多巴胺和罂粟碱治疗并没有改善 RCR,然而,ATP-MgCl2 治疗导致回流后 ADP/O 和 RCR 逐渐显着升高。研究发现,经盐水、多巴胺和罂粟碱治疗的大鼠的肝脏 ATP 水平在回流后 3 小时降低了 50%,然而,用 ATP-MgCl2 治疗导致 ATP 水平和能量消耗显着升高。经盐水处理的大鼠的肝血流量在复流后 1 小时显着降低,但 ATP-MgCl2 组的肝血流量显着升高。复流后三小时,生理盐水处理的大鼠的肝血流量进一步减少,而 ATP-MgCl2 处理的大鼠的肝血流量逐渐增加。多巴胺治疗导致血流初步恢复,但这种效果并未持续。盐水治疗组大鼠的肝脏超微结构在​​复流后逐渐恶化,而ATP-MgCl2治疗组大鼠在复流后1小时和20小时肝脏超微结构正常。这些结果使我们得出结论,输注 ATP-MgCl2 可以直接改善线粒体和细胞功能,或者通过长期改善微循环,但不是通过血管舒张。
Infusion of ATP-MgCl2 following hepatic ischemia significantly improves the survival of animals. To determine the subcellular effects of infused ATP-MgCl2 and whether such effects are mediated through vasodilatation, global hepatic ischemia in rats was produced for 90 min followed by reperfusion. The rats then received iv 0.5 ml of saline, dopamine, papaverine, or ATP-MgCl2. At various intervals following reflow, hepatic mitochondria were isolated. ADP-to-O ratio and respiratory control ratio (RCR) were significantly lower 1 h following reflow, and there was a further decrease in these parameters 3 h after reflow in mitochondria from saline-treated rats. Dopamine and papaverine treatment did not improve RCR, however, ATP-MgCl2 treatment resulted in a progressive and significantly higher ADP/O and RCR following reflow. Hepatic ATP levels in saline, dopamine, and papaverine-treated rats were found to be 50% lower 3 h following reflow, however, treatment with ATP-MgCl2 resulted in significantly higher ATP levels and energy charge. Hepatic blood flow was markedly depressed 1 h following reflow in the saline-treated rats but was significantly higher in the ATP-MgCl2 group. Three hours following reflow, hepatic blood flow decreased further in the saline-treated rats, whereas in the ATP-MgCl2-treated rats there was a progressive increase in flow. Dopamine treatment resulted in an initial restoration in flow, however, this effect was not sustained. Hepatic ultrastructure deteriorated progressively following reflow in the saline-treated rats, however, it was normal in the ATP-MgCl2-treated rats 1 h as well as 20 h following reflow. These results lead us to conclude that infused ATP-MgCl2 improves mitochondrial and cellular functions either directly or by way of long-term improvement in microcirculation but not through vasodilatation.