BACKGROUND: Ischemia/reperfusion is the main cause of hepatic damage in liver transplantation. Immediate early genes (IEGs) encode proteins can regulate expression of cellular response genes after injury, and is assoc...BACKGROUND: Ischemia/reperfusion is the main cause of hepatic damage in liver transplantation. Immediate early genes (IEGs) encode proteins can regulate expression of cellular response genes after injury, and is associated with tissue repair and cell apoptosis. The purpose of this re- search was to investigate the effects of preconditioning on expression of immediate early genes c-fos and c-jun follow- ing hepatic ischemia/reperfusion (IR) and its roles in cellu- lar regeneration and apoptosis. METHODS: Ninety-six Wistar rats were randomly divided into IR group and hepatic ischemic preconditioning (IPC) group, and each group was further divided into eight sub- groups (n =6). The model of partial liver ischemia/reper- fusion was used. The rats were subjected to 60-minute liver ischemia, preceded by 10-minute preconditioning. After 0-, 0.5-, 1-, 2-, 4-, 8-, 12-, 24-hour reperfusion, the se- rum and liver tissue in each group were collected to detect the level of serum ALT/AST, liver histopathology, expres- sion of c-fos, and c-jun mRNA. Flow cytometer was used to detect Ki67 and Sub-G1 as the quantity indicators of cell regeneration and apoptosis respectively. RESULTS: Compared with IR group, IPC group showed a significantly lower ALT/AST level in 0. 5-hour sub-group to 8-hour sub-group (P<0.05). Ki67 elevated significantly at 0.5, 1, 2 hours, but decreased significantly at 24 hours ( P < 0 . 05). Ap index decreased significantly after 1-hour reperfusion(P<0.05). Expressions of c-fos and c-jun mR- NA were low, especially c-jun at 0.5, 1 and 2 hours after reperfusion. CONCLUSION: Ischemic preconditioning can protect liver cells against ischemia/reperfusion injury, and this protec- tive effect may be related to influence transcription levels of c-fos and c-jun.展开更多
The effect of Batroxobin on expression of c-Jun in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemistry methods. The results showed that...The effect of Batroxobin on expression of c-Jun in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats for searching a goal were significantly longer than those of sham-operated rats, and at the same time c-Jun expression of left temporal ischemic region was significantly increased. However, the mean reaction time and distance of Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of c-Jun immune reactive cells of Batroxobin-treated rats was also less than that of ischemic group. In conclusion, Batroxobin can improve spatial memory disorder in temporal ischemic rats, and the down-regulation of the expression of c-Jun is probably related to the neuroprotective mechanism.展开更多
The micro RNA（mi RNA） let-7 was one of the first mi RNAs to be discovered, and is highly conserved and widely expressed among species. let-7 expression increases in brain tissue after cerebral ischemia/reperfusion i...The micro RNA（mi RNA） let-7 was one of the first mi RNAs to be discovered, and is highly conserved and widely expressed among species. let-7 expression increases in brain tissue after cerebral ischemia/reperfusion injury; however, no studies have reported let-7 effects on nerve injury after cerebral ischemia/reperfusion injury. To investigate the effects of let-7 gene knockdown on cerebral ischemia/reperfusion injury, we established a rat model of cerebral ischemia/reperfusion injury. Quantitative reverse transcription-polymerase chain reaction demonstrated that 12 hours after cerebral ischemia/reperfusion injury, let-7 expression was up-regulated, peaked at 24 hours, and was still higher than that in control rats after 72 hours. Let-7 gene knockdown in rats suppressed microglial activation and inflammatory factor release, reduced neuronal apoptosis and infarct volume in brain tissue after cerebral ischemia/reperfusion injury. Western blot assays and luciferase assays revealed that mitogen-activated protein kinase phosphatase-1（MKP1） is a direct target of let-7. Let-7 enhanced phosphorylated p38 mitogen-activated protein kinase（MAPK） and c-Jun N-terminal kinase（JNK） expression by down-regulating MKP1. These findings suggest that knockdown of let-7 inhibited the activation of p38 MAPK and JNK signaling pathways by up-regulating MKP1 expression, reduced apoptosis and the inflammatory reaction, and exerted a neuroprotective effect following cerebral ischemia/reperfusion injury.展开更多
文摘BACKGROUND: Ischemia/reperfusion is the main cause of hepatic damage in liver transplantation. Immediate early genes (IEGs) encode proteins can regulate expression of cellular response genes after injury, and is associated with tissue repair and cell apoptosis. The purpose of this re- search was to investigate the effects of preconditioning on expression of immediate early genes c-fos and c-jun follow- ing hepatic ischemia/reperfusion (IR) and its roles in cellu- lar regeneration and apoptosis. METHODS: Ninety-six Wistar rats were randomly divided into IR group and hepatic ischemic preconditioning (IPC) group, and each group was further divided into eight sub- groups (n =6). The model of partial liver ischemia/reper- fusion was used. The rats were subjected to 60-minute liver ischemia, preceded by 10-minute preconditioning. After 0-, 0.5-, 1-, 2-, 4-, 8-, 12-, 24-hour reperfusion, the se- rum and liver tissue in each group were collected to detect the level of serum ALT/AST, liver histopathology, expres- sion of c-fos, and c-jun mRNA. Flow cytometer was used to detect Ki67 and Sub-G1 as the quantity indicators of cell regeneration and apoptosis respectively. RESULTS: Compared with IR group, IPC group showed a significantly lower ALT/AST level in 0. 5-hour sub-group to 8-hour sub-group (P<0.05). Ki67 elevated significantly at 0.5, 1, 2 hours, but decreased significantly at 24 hours ( P < 0 . 05). Ap index decreased significantly after 1-hour reperfusion(P<0.05). Expressions of c-fos and c-jun mR- NA were low, especially c-jun at 0.5, 1 and 2 hours after reperfusion. CONCLUSION: Ischemic preconditioning can protect liver cells against ischemia/reperfusion injury, and this protec- tive effect may be related to influence transcription levels of c-fos and c-jun.
文摘The effect of Batroxobin on expression of c-Jun in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats for searching a goal were significantly longer than those of sham-operated rats, and at the same time c-Jun expression of left temporal ischemic region was significantly increased. However, the mean reaction time and distance of Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of c-Jun immune reactive cells of Batroxobin-treated rats was also less than that of ischemic group. In conclusion, Batroxobin can improve spatial memory disorder in temporal ischemic rats, and the down-regulation of the expression of c-Jun is probably related to the neuroprotective mechanism.
基金supported by the National Natural Science Foundation of China,No.81460193
文摘The micro RNA（mi RNA） let-7 was one of the first mi RNAs to be discovered, and is highly conserved and widely expressed among species. let-7 expression increases in brain tissue after cerebral ischemia/reperfusion injury; however, no studies have reported let-7 effects on nerve injury after cerebral ischemia/reperfusion injury. To investigate the effects of let-7 gene knockdown on cerebral ischemia/reperfusion injury, we established a rat model of cerebral ischemia/reperfusion injury. Quantitative reverse transcription-polymerase chain reaction demonstrated that 12 hours after cerebral ischemia/reperfusion injury, let-7 expression was up-regulated, peaked at 24 hours, and was still higher than that in control rats after 72 hours. Let-7 gene knockdown in rats suppressed microglial activation and inflammatory factor release, reduced neuronal apoptosis and infarct volume in brain tissue after cerebral ischemia/reperfusion injury. Western blot assays and luciferase assays revealed that mitogen-activated protein kinase phosphatase-1（MKP1） is a direct target of let-7. Let-7 enhanced phosphorylated p38 mitogen-activated protein kinase（MAPK） and c-Jun N-terminal kinase（JNK） expression by down-regulating MKP1. These findings suggest that knockdown of let-7 inhibited the activation of p38 MAPK and JNK signaling pathways by up-regulating MKP1 expression, reduced apoptosis and the inflammatory reaction, and exerted a neuroprotective effect following cerebral ischemia/reperfusion injury.
