Phshoenol/pyruvate prevents the decline in hepatic ATP and energy charge afte ischemia and reperfusion injyury in rats

酚/丙酮酸可防止大鼠缺血再灌注损伤后肝脏 ATP 和能量消耗的下降

• 批准号: 07671405
• 负责人: YAMAGUCHI Koji
• 金额: $ 1.54万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671405/
• 关键词: phosphoenolpyruvate; warm ischemia of the liver; hepatic energy; ホスホエノールピルビン酸; 肝虚血再環流; ラット; エネルギーチャージ; 解糖系; 肝虚血・再環流障害

Phsophoeneolpyruvate (PEP) is a high energy metabolite in the final step of glycolysis. PEP is converted into pyruvate by pyruvate kinase. One molecule of adenosine triphosphate (ATP) is generate from one molecule of PEP.The aim of this study was to examine the effects of PEP on hepatic energy metabolism at an early phase after ischemia and reperfusion in rats. Male Wister rats (250-350g) were divided into two groups ; after two 15-min periods of ischemia with 2 min reperfusion in between, either PEP or glucose solution (400mmol/liter, pH7.4) was infused into the portal vein (2.5ml/300g body wt/5min). Before and 0,5,10 and 30 min after ischemia, arterial blood and liver tissue were collected fo analyzes. Results : During the two ischemic periods, ATP and total adenine nucleotide (TAN) of the liver decreased from 9.10(]SY.+-。[)0.50 and 14.06(]SY.+-。[)0.29 to 0.99(]SY.+-。[)0.50 and 10.86(]SY.+-。[)0.42mmole/g liver, respectively (P<0.05), while adenosine monophoshate (AMP) increased from … More 1.18(]SY.+-。[)0.15 to 8.47(]SY.+-。[)0.6mmole/g liver (P<0.05). Hepatic energy charge (EC) significantly decreased from 0.78(]SY.+-。[)0.02 to 0.16(]SY.+-。[)0.03 (P<0.005). Serum concentration of pyruvate and lactate were elevated from 1.18(]SY.+-。[)0.15 and 18. (]SY.+-。[)0.52 to 3.29(]SY.+-。[)0.52 and 72.6(]SY.+-。[)4.8mg/dl, respectively (P<0.05). After a 5-min infusion of PEP or glucose solution, the ATP concentration was significantly higher in the PEP group than in the glucose grc (4.08(]SY.+-。[)0.58mumole/g liver vs 2.20(]SY.+-。[)0.45mumole/g liver, P<0.01), whereas AMP concentration was significantly lower in the PEP group than in the glucose group (4.26(]SY.+-。[)0.66mumole/g liver vs 7.02(]SY.+-。[)0.71mumole/g liver, P<0.01). EC in the PEP group was significantly higher than that in the PEP group (0.493 : 0.051 vs 0.293(]SY.+-。[)0.042, P<0.01). Ten minutes after ischemia, the ATP,TAN,and EC level were still higher in the PEP group than in the glucose group, the difference did not reach statistical significance. A min after ischemia, these values became similar in both groups. At 5,10, and 30 min after ischemia, serum pyruvate concentrations were higher in the PEP group than in the glucose group. Conclusion : The findings suggest that PEP recover hepatic energy from liver cell damage at an early phase after ischmeia reperfusion by prompt ATP production through the degradation of PEP into pyruvate in the liver. Less

磷酸烯醇丙酮酸（PEP）是糖酵解最后一步的高能量代谢物。PEP通过丙酮酸激酶转化为丙酮酸。一个PEP分子产生一个三磷酸腺苷（ATP）分子。本研究旨在探讨PEP对大鼠缺血再灌注后早期肝脏能量代谢的影响。雄性Wister大鼠（250 ~ 350g）分为两组；缺血15 min，再灌注2 min后，分别向门静脉输注PEP或葡萄糖溶液（400mmol/l, pH7.4） （2.5ml/300g body wt/5min）。分别于缺血前、缺血后0、5、10、30 min采集动脉血和肝组织进行分析。结果：缺血期间，肝脏ATP和总腺嘌呤核苷酸（TAN）分别从9.10(]SY.+-[)0.50和14.06(]SY.+-[)0.29降至0.99(]SY.+-[)0.50和10.86(]SY.+- [)0.42mmol /g肝脏（P<0.05），而单磷酸腺苷（AMP）从1.18(]SY.+-[)0.15升高至8.47(]SY.+- [)0.6mmol /g肝脏（P<0.05）。肝脏能量电荷（EC）由0.78(]SY.+- .[)0.02显著降低至0.16(]SY.+- . [)0.03 （P<0.005）。血清丙酮酸和乳酸浓度分别从1.18（0.05）和1.18（0.05）升高。(SY。+ -。)0.52 - 3.29 (SY。+ -。)(SY。+ - 0.52和72.6。(分别)4.8 mg / dl (P < 0.05)。PEP或葡萄糖溶液输注5 min后，PEP组ATP浓度显著高于葡萄糖组(4.08(]SY.+- [)0.58mumole/g肝脏vs 2.20(]SY.+- [)0.45mumole/g肝脏，P<0.01)，而PEP组AMP浓度显著低于葡萄糖组(4.26（]SY.+- [)0.66mumole/g肝脏vs 7.02(]SY.+- [)0.71mumole/g肝脏，P<0.01）。PEP组EC显著高于PEP组（0.493:0.051 vs 0.293(]SY.+- . [)0.042， P<0.01）。缺血10分钟后，PEP组ATP、TAN、EC水平仍高于葡萄糖组，差异无统计学意义。缺血1分钟后，两组的这些数值相似。缺血后5、10、30分钟，PEP组血清丙酮酸浓度高于葡萄糖组。结论：PEP可在缺血再灌注后早期恢复肝细胞损伤的肝脏能量，其机制是通过PEP在肝脏中降解为丙酮酸而促进ATP的生成。少

项目成果

Shuji Saeki, Koji Yamaguchi, Kazuo Chijiiwa, Shuji Shimizu, Naotaka Hamasaki, Masao Tanaka.: "Phosphoenolpyruvate prevents the decline in hepatic ATP and energy charge after ischemia and reperfusion injyury rats" Journal of Surgical Research. 73(1). 59-65

Shuji Saeki、Koji Yamaguchi、Kazuo Chijiiwa、Shuji Shimizu、Naotaka Hamasaki、Masao Tanaka.：“磷酸烯醇丙酮酸可防止大鼠缺血和再灌注损伤后肝脏 ATP 和能量的下降”《外科研究杂志》。

Shuji Saeki et al.: "Phosphoenol pyruvate prevents the decline in hepatic ATP and energy charge after ischemia and reperfusion injury in rats" Journal of Surgical Research. 73. 59-65 (1997)

Shuji Saeki 等人：“磷酸烯醇丙酮酸可防止大鼠缺血和再灌注损伤后肝脏 ATP 和能量电荷的下降”《外科研究杂志》。

Syhji Saeki et al.: "Phosphoenol pyruvate prevents the decline in hepatic ATP and energy charge after ischemia and reperfusion injury in rats" Journal of surgical Research. 73. 59-65 (1997)

Syhji Saeki 等人：“磷酸烯醇丙酮酸可防止大鼠缺血和再灌注损伤后肝脏 ATP 和能量电荷的下降”《外科研究杂志》。