The protective effects of shikonin on hepatic ischemia/reperfusion injury are mediated by the activation of the PI3K/Akt pathway.
Hepatic ischemia/reperfusion (I/R) injury, which can result in severe liver injury and dysfunction, occurs in a variety of conditions such as liver transplantation, shock, and trauma. Cell death in hepatic I/R injury has been linked to apoptosis and autophagy. Shikonin plays a significant protective role in ischemia/reperfusion injury. The purpose of the present study was to investigate the protective effect of shikonin on hepatic I/R injury and explore the underlying mechanism. Mice were subjected to segmental (70%) hepatic warm ischemia to induce hepatic I/R injury. Two doses of shikonin (7.5 and 12.5 mg/kg) were administered 2 h before surgery. Balb/c mice were randomly divided into four groups: normal control, I/R, and shikonin preconditioning at two doses (7.5 and 12.5 mg/kg). The serum and liver tissues were collected at three time points (3, 6, and 24 h). Shikonin significantly reduced serum AST and ALT levels and improved pathological features. Shikonin affected the expression of Bcl-2, Bax, caspase 3, caspase 9, Beclin-1, and LC3, and upregulated PI3K and p-Akt compared with the levels in the I/R group. Shikonin attenuated hepatic I/R injury by inhibiting apoptosis and autophagy through a mechanism involving the activation of PI3K/Akt signaling.
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Tong
T
Liu
Department of Clinical Laboratory, Kunshan First People's Hospital Affiliated to Jiangsu University, 215300, Kunshan, JiangSu, China.
QingHui
Q
Zhang
Department of Gastroenterology, Minhang Hospital, Shanghai Medical School of Fudan University, Shanghai, 201100, China.
Wenhui
W
Mo
Department of Gastroenterology, Shanghai Tenth Hospital, School of Clinical Medicine of Nanjing Medical University, Shanghai 200072, China.
Qiang
Q
Yu
Department of Gastroenterology, Shanghai Tenth Hospital, School of Clinical Medicine of Nanjing Medical University, Shanghai 200072, China.
Shizan
S
Xu
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Jingjing
J
Li
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Sainan
S
Li
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Jiao
J
Feng
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Liwei
L
Wu
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Xiya
X
Lu
Department of Gastroenterology, Shanghai Tenth Hospital, School of Clinical Medicine of Nanjing Medical University, Shanghai 200072, China.
Rong
R
Zhang
The School of Medicine of Soochow University, Suzhou 215006, China.
Linqiang
L
Li
The School of Medicine of Soochow University, Suzhou 215006, China.
Keran
K
Cheng
The School of Medicine of Soochow University, Suzhou 215006, China.
Yuqing
Y
Zhou
The School of Medicine of Soochow University, Suzhou 215006, China.
Shunfeng
S
Zhou
The School of Medicine of Soochow University, Suzhou 215006, China.
Rui
R
Kong
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Fan
F
Wang
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Weiqi
W
Dai
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Kan
K
Chen
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Yujing
Y
Xia
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Jie
J
Lu
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Yingqun
Y
Zhou
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Yan
Y
Zhao
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Chuanyong
C
Guo
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004121:Dimethyl Sulfoxide; D004789:Enzyme Activation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D008111:Liver Function Tests; D008297:Male; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009285:Naphthoquinones / Q000494:pharmacology / Q000627:therapeutic use*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction
D016207:Cytokines; D018836:Inflammation Mediators; D009285:Naphthoquinones; D020011:Protective Agents; C016101:shikonin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D004121:Dimethyl Sulfoxide