Simple regulation of c-Jun N-terminal kinase（JNK） or p38 mitogen-activated protein kinase（MAPK） pathways is not enough to trigger cell apoptosis.However,activation of the stress activated pathway（JNK/p38 MAPK） t...Simple regulation of c-Jun N-terminal kinase（JNK） or p38 mitogen-activated protein kinase（MAPK） pathways is not enough to trigger cell apoptosis.However,activation of the stress activated pathway（JNK/p38 MAPK） together with inhibition of the growth factor activated extracellular signal-regulated kinase（ERK） pathway can promote cell apoptosis.We hypothesized that inhibition of the JNK or p38 pro-apoptotic pathway and activating the ERK pathway could be the mechanism of anti-apoptosis following cerebral ischemia/reperfusion injury.To investigate the mechanism of the protective effect of electroacupuncture on cerebral ischemia/reperfusion injury in JNK knockout mice,mouse models of cerebral ischemia/reperfusion injury were established by Longa’s method.Electroacupuncture was conducted at acupoints Chize（LU5）,Hegu（LI4）,Sanyinjiao（SP6） and Zusanli（ST36） 1.5 hours after ischemia/reperfusion injury for 20 minutes,once a day.The neurological function was evaluated using neurological deficit scores.The expression of phospho-extracellular signal-regulated kinase（p-ERK） and phospho-p38（p-p38） in JNK knockout mice was detected using double-labeling immunofluorescence and western blot assay.The m RNA expression of ERK and p38 was measured by quantitative real-time polymerase chain reaction.Electroacupuncture improved neurological function,increased the immunoreactivity and relative expression of p-ERK and reduced that of p-p38 in the cerebral cortex and hippocampus on the injured side.Electroacupuncture increased m RNA expression of ERK,but decreased that of p38 in the cerebral cortex and hippocampus on the injured side.In conclusion,electroacupuncture upregulated the protective ERK pathway and inhibited the pro-apoptotic p38 pathway,thereby exerting a neuroprotective effect and improving the neurological function in JNK knockout mice.展开更多
基金supported by the National Natural Science Foundation of China,No.81173355
文摘Simple regulation of c-Jun N-terminal kinase（JNK） or p38 mitogen-activated protein kinase（MAPK） pathways is not enough to trigger cell apoptosis.However,activation of the stress activated pathway（JNK/p38 MAPK） together with inhibition of the growth factor activated extracellular signal-regulated kinase（ERK） pathway can promote cell apoptosis.We hypothesized that inhibition of the JNK or p38 pro-apoptotic pathway and activating the ERK pathway could be the mechanism of anti-apoptosis following cerebral ischemia/reperfusion injury.To investigate the mechanism of the protective effect of electroacupuncture on cerebral ischemia/reperfusion injury in JNK knockout mice,mouse models of cerebral ischemia/reperfusion injury were established by Longa’s method.Electroacupuncture was conducted at acupoints Chize（LU5）,Hegu（LI4）,Sanyinjiao（SP6） and Zusanli（ST36） 1.5 hours after ischemia/reperfusion injury for 20 minutes,once a day.The neurological function was evaluated using neurological deficit scores.The expression of phospho-extracellular signal-regulated kinase（p-ERK） and phospho-p38（p-p38） in JNK knockout mice was detected using double-labeling immunofluorescence and western blot assay.The m RNA expression of ERK and p38 was measured by quantitative real-time polymerase chain reaction.Electroacupuncture improved neurological function,increased the immunoreactivity and relative expression of p-ERK and reduced that of p-p38 in the cerebral cortex and hippocampus on the injured side.Electroacupuncture increased m RNA expression of ERK,but decreased that of p38 in the cerebral cortex and hippocampus on the injured side.In conclusion,electroacupuncture upregulated the protective ERK pathway and inhibited the pro-apoptotic p38 pathway,thereby exerting a neuroprotective effect and improving the neurological function in JNK knockout mice.
