Hepatocyte apoptosis is enhanced after ischemia/reperfusion in the steatotic liver.
Hepatocyte apoptosis is enhanced after ischemia/reperfusion in the steatotic liver.
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DOI：
10.3164/jcbn.10-74
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发表时间：
2011-03
影响因子：
2.4
通讯作者：
Miyazaki M
中科院分区：
文献类型：
--
作者：
Suzuki T;Yoshidome H;Kimura F;Shimizu H;Ohtsuka M;Takeuchi D;Kato A;Furukawa K;Yoshitomi H;Iida A;Dochi T;Miyazaki M
肝脏脂肪变性与肝脏切除和移植后的器官功能障碍有关，可能是由于肝脏缺血/再灌注损伤引起的。本研究的目的是确定脂肪变性肝缺血/再灌注后导致肝细胞凋亡的确切机制。使用小鼠模型的部分肝缺血90分钟，我们研究了细胞凋亡的水平和途径，和过氧亚硝酸盐的表达，血清丙氨酸氨基转移酶水平，和肝脏组织学再灌注后1和4小时。在脂肪肝，过氧亚硝基表达增加缺血/再灌注后。再灌注后脂肪变性肝脏中观察到显著的肝细胞凋亡，这是由裂解的半胱天冬酶9和3的上调引起的，但不是半胱天冬酶8。血清丙氨酸氨基转移酶水平升高，组织学检查显示，在脂肪肝再灌注后4小时严重的肝损伤。在用氨基胍治疗的小鼠中，与用磷酸盐缓冲盐水治疗的小鼠相比，脂肪变性肝脏中缺血/再灌注诱导的血清丙氨酸氨基转移酶水平升高和细胞凋亡显著减少。用氨基胍治疗脂肪肝小鼠的存活率显著提高。我们的数据表明，脂肪变性的肝脏是容易受到肝脏缺血/再灌注，导致显着的肝细胞凋亡的线粒体通透性转换，从而导致器官功能障碍。
Liver steatosis is associated with organ dysfunction after hepatic resection and transplantation which may be caused by hepatic ischemia/reperfusion injury. The aim of the current study was to determine the precise mechanism leading to hepatocyte apoptosis after steatotic liver ischemia/reperfusion. Using a murine model of partial hepatic ischemia for 90 min, we examined the levels and pathway of apoptosis, and the peroxynitrite expression, serum alanine aminotransferase levels, and liver histology 1 and 4 h after reperfusion. In the steatotic liver, the peroxynitrite expression increased after ischemia/reperfusion. Significant hepatocyte apoptosis in the steatotic liver was seen after reperfusion, caused by upregulation of cleaved caspases 9 and 3, but not caspase 8. Serum alanine aminotransferase levels were elevated and histological examination revealed severe liver injury in the steatotic liver 4 h after reperfusion. In mice treated with aminoguanidine, ischemia/reperfusion-induced increases in serum alanine aminotransferase levels and apoptosis were significantly reduced in steatotic liver compared with mice treated with phosphate buffered saline. Survival of mice with steatotic livers significantly improved by treatment with aminoguanidine. Our data suggested that the steatotic liver is vulnerable to hepatic ischemia/reperfusion, leading to significant hepatocyte apoptosis by the mitochondrial permeability transition, and thereby resulting in organ dysfunction.
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影响因子：
3.2
作者：
Kooby, DA;Fong, Y;Jarnagin, WR
通讯作者：
Jarnagin, WR
影响因子：
2.4
作者：
Sakuragawa, Tadayuki;Hishiki, Takako;Suematsu, Makoto
通讯作者：
Suematsu, Makoto
DOI：
10.1152/ajpgi.2001.281.4.g1115
发表时间：
2001-10-01
影响因子：
4.5
作者：
Soeda, J;Miyagawa, S;Kawasaki, S
通讯作者：
Kawasaki, S
影响因子：
13.5
作者：
Takeuchi, D;Yoshidome, H;Miyazaki, M
通讯作者：
Miyazaki, M
影响因子：
13.5
作者：
Vendemiale, G;Grattagliano, I;Altomare, E
通讯作者：
Altomare, E