机构：[1]Department of Hepatopancreatobiliary Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Calmette Hospital, Kunming, Yunnan Province, China[2]Department of Hepatopancreatobiliary, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan Province, China外科片肝胆外科云南省第一人民医院
This study was conducted to investigate the effect of warm ischemia duration on hepatocyte mitochondrial damage after liver transplantation, and confirm the role of CaMKII gamma in this process. Rat donation after cardiac death (DCD) liver transplantation model was established by exposing donor liver to 0 (W-0 group), 15 (W-15 group), and 30 (W-30 group) min warm ischemia. Some rats in W-15 group were transfected with CaMKII gamma and CaMKII gamma-shRNA lentivirus. On day 1, 3, and 7 post-transplantation, a series of experiments, including HE staining, TEM observation, ALT and AST measurement, flow cytometry analysis, qRT-PCR, and Western blotting were performed to evaluate the extent of hepatic and mitochondria damage. Within 7 days post-transplantation, prolonged ischemia led to an obvious deterioration of hepatic and mitochondria damage, presenting with a marked increase of apoptotic hepatocytes, ALT and AST levels, cells with low MMP, and AIF and Cyt C expression. CaMKII gamma overexpression caused the significant ultrastructural damage of hepatic cells, increase of cells with low MMP, enhancement of AIF and Cyt C expression, and augmented Ca2+/CaM/CaMKII gamma, while blocking CaMKII gamma showed an opposite result. In conclusion, ischemia duration is proportional to the extent of hepatic mitochondria damage, and CaMKII gamma plays a negative regulatory role in this process by regulating the Ca2+/CaM/CaMKII signaling pathway.
基金：
This study was supported by Joint project funds of Yunnan Provincial Science and Technology Department-Kunming Medical University, P. R. China (Grant No.: 2015FA010).
第一作者机构：[1]Department of Hepatopancreatobiliary Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Calmette Hospital, Kunming, Yunnan Province, China[2]Department of Hepatopancreatobiliary, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan Province, China
通讯作者：
通讯机构：[1]Department of Hepatopancreatobiliary Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Calmette Hospital, Kunming, Yunnan Province, China[*1]Department of Hepatopancreatobiliary Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Calmette Hospital, 1228 Beijing Road, Panlong District, Kunming 650224, Yunnan Province, China.
推荐引用方式(GB/T 7714)：
Zhang Li,Zhang Sheng-Ning,Li Li,et al.Prolonged warm ischemia aggravates hepatic mitochondria damage and apoptosis in DCD liver by regulating Ca2+/CaM/CaMKII signaling pathway[J].INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY.2019,12(1):217-228.
APA：
Zhang, Li,Zhang, Sheng-Ning,Li, Li,Zhang, Xi-Bing,Wu, Rui-Chao...&Ran, Jiang-Hua.(2019).Prolonged warm ischemia aggravates hepatic mitochondria damage and apoptosis in DCD liver by regulating Ca2+/CaM/CaMKII signaling pathway.INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY,12,(1)
MLA：
Zhang, Li,et al."Prolonged warm ischemia aggravates hepatic mitochondria damage and apoptosis in DCD liver by regulating Ca2+/CaM/CaMKII signaling pathway".INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 12..1(2019):217-228
