Objective： To examine modulations caused by cyclooxygenase-2 （COX-2） inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possib...Objective： To examine modulations caused by cyclooxygenase-2 （COX-2） inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possible mechanisms. Methods： Celecoxib （a COX-2 inhibitor） was administered 45 min prior to pilocarpine administration. The effects of COX-2 inhibitors on mlPSCs （miniature GABAergic inhibitory postsynaptic currents） of CA3 pyramidal cells in the hippocampus were recorded. Expressions of COX-2, c-Fos, newly generated neurons, and activated microgliosis were analyzed by immunohistochemistry, and expressions of c^-subunit of y-amino butyric acid （GABAA） receptors and mitogen-activated protein kinase/extracellular signal-regulated protein kinase （MAPK/ERK） activity were detected by Western blotting. Results： Pretreatment with celecoxib showed protection against pilocarpine-induced seizures. Celecoxib prevented microglia activation in the hilus and inhibited the abnormal neurogenesis and astrogliosis in the hippocampus by inhibiting MAPK/ERK activity and c-Fos transcription. Celecoxib also up-regulated the expression of GABAA receptors. NS-398 （N-2-cyclohexyloxy-4-nitrophenyl-methanesulfonamide）, another COX-2 inhibitor, enhanced the frequency and decay time of mIPSCs. Conclusion： The COX-2 inhibitor celecoxib decreased neuronal excitability and prevented epileptogenesis in pilocarpine-induced status epilepticus rats. Celecoxib regulates synaptic reorganization by inhibiting astrogliosis and ectopic neurogenesis by attenuating MAPK/ERK signal activity, mediated by a GABAergic mechanism.展开更多
This paper reported the contents variation analysis ofγ-amino butyric acid(GABA)in Semen sojae praeparatum(SSP)which is a famous traditional Chinese medicine.High performance liquid chromatography(HPLC)was used and G...This paper reported the contents variation analysis ofγ-amino butyric acid(GABA)in Semen sojae praeparatum(SSP)which is a famous traditional Chinese medicine.High performance liquid chromatography(HPLC)was used and GABA was derivatized by online pre-column derivatization with o-phthalaldehyde(OPA).To validate this method,the precision,stability,repeatability and recovery were discussed.In the concentration range from 0.0125 to 0.400 mg/m L,the calibration curve for GABA was linear and the regression equation was obtained with correlation coefficient(R2)of 0.9999.Relatively high levels of GABA exist in SSP and the content changes of GABA at different time points during the fermenting process were detected.At the"yellow cladding"stage,GABA level was very low or even undetectable;the"secondary fermentation"stage witnessed a rapid increase of GABA content to 1.39-5.52 mg/g,which remained stable after 18 days of"secondary fermentation".This study demonstrated that GABA was generated at the"secondary fermentation"stage,revealing the significance and rationality of the"secondary fermentation"stage in the fermenting process of SSP.On the other hand,it suggested the downside of taking soy isoflavones as the only measurement in existing quality assessment and optimization approach for the fermenting process of SSP.展开更多
文摘Objective： To examine modulations caused by cyclooxygenase-2 （COX-2） inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possible mechanisms. Methods： Celecoxib （a COX-2 inhibitor） was administered 45 min prior to pilocarpine administration. The effects of COX-2 inhibitors on mlPSCs （miniature GABAergic inhibitory postsynaptic currents） of CA3 pyramidal cells in the hippocampus were recorded. Expressions of COX-2, c-Fos, newly generated neurons, and activated microgliosis were analyzed by immunohistochemistry, and expressions of c^-subunit of y-amino butyric acid （GABAA） receptors and mitogen-activated protein kinase/extracellular signal-regulated protein kinase （MAPK/ERK） activity were detected by Western blotting. Results： Pretreatment with celecoxib showed protection against pilocarpine-induced seizures. Celecoxib prevented microglia activation in the hilus and inhibited the abnormal neurogenesis and astrogliosis in the hippocampus by inhibiting MAPK/ERK activity and c-Fos transcription. Celecoxib also up-regulated the expression of GABAA receptors. NS-398 （N-2-cyclohexyloxy-4-nitrophenyl-methanesulfonamide）, another COX-2 inhibitor, enhanced the frequency and decay time of mIPSCs. Conclusion： The COX-2 inhibitor celecoxib decreased neuronal excitability and prevented epileptogenesis in pilocarpine-induced status epilepticus rats. Celecoxib regulates synaptic reorganization by inhibiting astrogliosis and ectopic neurogenesis by attenuating MAPK/ERK signal activity, mediated by a GABAergic mechanism.
基金the National Natural Science Foundation of China(81660664,82060709,82060699)the Natural Science Foundation of Jiangxi Province(20192ACBL21032,20192BBGL70051)China Scholarship Council(201908360259)。
文摘This paper reported the contents variation analysis ofγ-amino butyric acid(GABA)in Semen sojae praeparatum(SSP)which is a famous traditional Chinese medicine.High performance liquid chromatography(HPLC)was used and GABA was derivatized by online pre-column derivatization with o-phthalaldehyde(OPA).To validate this method,the precision,stability,repeatability and recovery were discussed.In the concentration range from 0.0125 to 0.400 mg/m L,the calibration curve for GABA was linear and the regression equation was obtained with correlation coefficient(R2)of 0.9999.Relatively high levels of GABA exist in SSP and the content changes of GABA at different time points during the fermenting process were detected.At the"yellow cladding"stage,GABA level was very low or even undetectable;the"secondary fermentation"stage witnessed a rapid increase of GABA content to 1.39-5.52 mg/g,which remained stable after 18 days of"secondary fermentation".This study demonstrated that GABA was generated at the"secondary fermentation"stage,revealing the significance and rationality of the"secondary fermentation"stage in the fermenting process of SSP.On the other hand,it suggested the downside of taking soy isoflavones as the only measurement in existing quality assessment and optimization approach for the fermenting process of SSP.
