Hepatoprotective effect of a nonselective endothelin receptor antagonist (TAK-044) in the transplanted liver.
Hepatoprotective effect of a nonselective endothelin receptor antagonist (TAK-044) in the transplanted liver.
复制标题
非选择性内皮素受体拮抗剂 (TAK-044) 在移植肝脏中的保肝作用。
作者：
N. Yamanaka;Y. Takaya;T. Oriyama;K. Furukawa;T. Tanaka;W. Tanaka;N. Ichikawa;C. Yasui;T. Ando;J. Yamanaka;N. Kuroda;M. Ko;M. Takada;M. Imakita;Y. Kitayama;E. Okamoto;S. Sasaki;I. Nakagaki;S. Hori;T. Ito
本研究旨在研究一种新型非选择性内皮素A/B（ETA/ET B）受体拮抗剂（TAK-044）是否在猪肝移植期间提供肝保护。将移植物储存在冷冻的Euro-Collins溶液中，并在含（TAK组）或不含（对照组）TAK-044（10 mg/kg）的乳酸林格氏液冲洗后再循环。细胞内（细胞质，线粒体和细胞核）钙（Ca）浓度进行了测量，连续获得的肝活检材料在不同的时间点，从供体剖腹手术受体关闭使用电子探针X射线显微分析仪。还测定了肝功能检查。两组移植物冷、热缺血时间相似。TAK组再循环后内皮素-1（T-1）峰值浓度显著高于对照组（129 +/- 30 pg/ml vs 26 +/- 6.5 pg/ml）。然而，TAK组的肝酶释放、总胆汁酸增加和吲哚菁绿色留存率恶化均受到显著抑制。在对照组中，肝动脉血流再循环后，细胞内Ca浓度，特别是线粒体组分中的Ca浓度显著升高。在TAK组中，该效应受到抑制。因此，通过冲洗途径补充使用非选择性ETA/ETB受体拮抗剂TAK-044可缓解肝移植物再灌注后早期微循环障碍，而不会因ET-1升高而对体循环产生不良影响。
This study was designed to investigate whether or not a novel nonselective endothelin A/B (ETA/ETB) receptor antagonist (TAK-044) provides hepatoprotection during porcine liver transplantation. The grafts were stored in chilled Euro-Collins solution and recirculated following reflush with lactated Ringer's with (TAK group) or without (control group) TAK-044 (10 mg/kg). Intracellular (cytoplasma, mitochondria, and nucleus) calcium (Ca) concentrations were measured in the hepatic biopsy materials obtained serially at varying time point from donor laparotomy to recipient closure using an electron probe X-ray microanalyzer. Liver function tests also were determined. The cold and warm ischemia times of the grafts were comparable between the two groups. The peak endothelin-1 T-1) concentration after recirculation was significantly higher in the TAK group than in the control group (129 +/- 30 pg/ml vs 26 +/- 6.5 pg/ml). However, release of liver enzymes, increases in total bile acid, and deterioration of indocyanine green retention rate were significantly suppressed in the TAK group. In the control group, the intracellular Ca concentrations, especially in the mitochondrial fraction, were elevated markedly following recirculation of the hepatic arterial flow. In the TAK group, this effect was suppressed. Thus, the supplementary use of the nonselective ETA/ETB receptor antagonist TAK-044 via a rinse route may alleviate an early postreperfusion microcirculatory disturbance of the liver grafts without adverse effects by the increased ET-1 on the systemic circulation.
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使用电子探针测量细胞钙和电子能量损失分析。
影响因子：
4
作者：
Somlyo,AP
通讯作者：
Somlyo,AP
内皮素-1 诱导肝窦直接收缩。
DOI：
10.1152/ajpgi.1994.266.4.g624
发表时间：
1994
期刊：
The American journal of physiology
影响因子：
--
作者：
Zhang,JX;PegoliJr,W;Clemens,MG
通讯作者：
Clemens,MG
原位肝移植后血浆内皮素升高与人体全身性高血压相关。
影响因子：
6.2
作者：
Lerman,A;Click,RL;Narr,BJ;Wiesner,RH;Krom,RA;Textor,SC;BurnettJr,JC
通讯作者：
BurnettJr,JC
对缺氧兔心肌中单个心肌细胞的元素组成进行定量 X 射线微量分析。
影响因子：
37.8
作者：
Buja,LM;Burton,KP;Hagler,HK;Willerson,JT
通讯作者：
Willerson,JT
影响因子：
4.1
作者：
GANDHI, CR;BEHAL, RH;OLSON, MS
通讯作者：
OLSON, MS