The long-term enhancement in glutamate receptor mediated excitatory responses has been observed in stroke model. This pathological form of plasticity, termed post-ischemic long-term potentiation （i-LTP）, points to f...The long-term enhancement in glutamate receptor mediated excitatory responses has been observed in stroke model. This pathological form of plasticity, termed post-ischemic long-term potentiation （i-LTP）, points to functional reorganization after stroke. Little is known, however, about whether and how this i-LTP would affect subsequent induction of synaptic plasticity. Here, we first directly confirmed that i-LTP was induced in the endothelin-l-induced ischemia model as in other in vitro models. We also demonstrated increased expression of NR2B, CaMKII and p-CaMKII, which are reminiscent of i-LTP. We further induced LTP of field excitatory post- synaptic potentials （fEPSPs） on CA1 hippocampal neurons in peri-infarct regions of the endothelin-l-induced mini-stroke model. We found that LTP of fEPSPs, induced by high-frequency stimulation, displayed a progressive impairment at 12 and 24 hours after ischemia. Moreover, using in vivo multi-channel recording, we found that the local field potential, which represents electrical property of cell ensembles in more restricted regions, was also dam- pened at these two time points. These results suggest that i-LTP elevates the induction threshold of subsequent synap- tic plasticity. Our data helps to deepen the knowledge of meta-synaptic regulation of plasticity after focal ischemia.展开更多
Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of ...Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of luteolin on nitric oxide （NO） formation in uric acid-stimulated Min6 cells using the Griess method. Next, we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor （NF）-κB. Western blotting assays were also performed to assess the effect of luteolin on the expression of MafA and inducible NO synthase （iNOS） in uric acid-treated cells. Finally, we evaluated the effect of luteolin on uric acidinduced inhibition of glucose-stimulated insulin secretion （GSIS） in Min6 cells and freshly isolated mouse pancreatic islets. We found that luteolin significantly inhibited uric acid-induced NO production, which was well correlated with reduced expression of iNOS mRNA and protein. Furthermore, decreased activity of NF-κB was implicated in inhibition by luteolin of increased iNOS expression induced by uric acid. Besides, luteolin significantly increased MafA expression in Min6 cells exposed to uric acid, which was reversed by overexpression of iNOS. Moreover, luteolin prevented uric acidinduced inhibition of GSIS in both Min6 cells and mouse islets. In conclusion, luteolin protects pancreatic β-cells from uric acid-induced dysfunction and may confer benefit on the protection of pancreatic β-cells in hyperuricemiaassociated diabetes.展开更多
Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is st...Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown. Here, we first established a mini-stroke model by infusion of endothelin-1 （ET-1） into the dorsal hippo- campus or the lateral amygdala, and then investigated how these mini-infarcts affected brain functions associated with these regions. We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory, but not in learning process and recall of tone fear memory. In novel object task, ET-1 in the hippocampus also elimi- nated object identity memory. ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear. These findings suggest that ET-1- induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.展开更多
Background Low potassium dextran （LPD） solution can attenuate acute lung injury （ALl）. However, LPD solution for treating acute kidney injury secondary to ALl has not been reported. The present study was performed...Background Low potassium dextran （LPD） solution can attenuate acute lung injury （ALl）. However, LPD solution for treating acute kidney injury secondary to ALl has not been reported. The present study was performed to examine the renoprotective effect of LPD solution in ALl induced by oleic acid （OA） in piglets. Methods Twelve animals that suffered an ALl induced by administration of OA into the right atrium were divided into two groups： the placebo group （n=6） pretreated with normal saline and the LPD group （n=6）, pretreated with LPD solution. LPD solution was injected intravenously at a dose of 12.5 ml/kg via the auricular vein 1 hour before OA injection. Results All animals survived the experiments with mild histopathological injury to the kidney. There were no significant differences in mean arterial pressure （MAP）, creatinin and renal damage scores between the two groups. Compared with the placebo group, the LPD group had better gas exchange parameters at most of the observation points （（347.0±12.6） mmHg vs. （284.3±11.3） mmHg at 6 hours after ALl, P 〈0.01）. After 6 hours of treatment with OA, the plasma concentrations of NGAL and intedeukin （IL）-6 in both groups increased dramatically compared to baseline （（6.0±0.6） and （2.50±0.08） folds in placebo group; and （2.5±0.5） and （1.40±0.05） folds in LPD group）, but the change of both parameters in the LPD group was significantly lower （P 〈0.01） than in the placebo group. And 6 hours after ALl the kidney tissue concentration of IL-6 in the LPD group （（165.7 ± 22.5） pg·m-1·g-1 protein） was significantly lower （P 〈0.01） than that in placebo group （（67.2± 25.3） pg·m-1·g-1 protein）. Conclusion These findings suggest that pretreatment with LPD solution via systemic administration might attenuate acute kidney injury and the cytokine response of IL-6 in the ALl piglet model induced by OA injection.展开更多
A stereotypical presentation of a hero in a Hollywood action movie would lavishly brag about not only strong muscle but also a large statue(a.k.a.bone structure),ostensibly for an attractive image.Unknown to these mov...A stereotypical presentation of a hero in a Hollywood action movie would lavishly brag about not only strong muscle but also a large statue(a.k.a.bone structure),ostensibly for an attractive image.Unknown to these movie producers is that the bone tissue does send a“sex-related”message,an endocrine message to be exact,to the male reproductive system.Maybe we shouldn’t blame Hollywood for their naivetéafter all;even in the scientific community,there is a long-held traditional belief that regards skeletal bone as merely a structural and supportive tissue.However,this view has been challenged by a series of recent studies.展开更多
基金supported by Major State Basic Research Program of China(Grant No.2013CB733801)
文摘The long-term enhancement in glutamate receptor mediated excitatory responses has been observed in stroke model. This pathological form of plasticity, termed post-ischemic long-term potentiation （i-LTP）, points to functional reorganization after stroke. Little is known, however, about whether and how this i-LTP would affect subsequent induction of synaptic plasticity. Here, we first directly confirmed that i-LTP was induced in the endothelin-l-induced ischemia model as in other in vitro models. We also demonstrated increased expression of NR2B, CaMKII and p-CaMKII, which are reminiscent of i-LTP. We further induced LTP of field excitatory post- synaptic potentials （fEPSPs） on CA1 hippocampal neurons in peri-infarct regions of the endothelin-l-induced mini-stroke model. We found that LTP of fEPSPs, induced by high-frequency stimulation, displayed a progressive impairment at 12 and 24 hours after ischemia. Moreover, using in vivo multi-channel recording, we found that the local field potential, which represents electrical property of cell ensembles in more restricted regions, was also dam- pened at these two time points. These results suggest that i-LTP elevates the induction threshold of subsequent synap- tic plasticity. Our data helps to deepen the knowledge of meta-synaptic regulation of plasticity after focal ischemia.
基金supported by the National Basic Research Program ofChina(2011CB504000,Program 973)the National Natural ScienceFoundation of China(81070656,81171589)the Colleges andUniversities in Jiangsu Province Plans to Graduate Research andInnovation(No.CXZZ12_0562)and Grant(No.100011)from the HealthDepartment of Sichuan Province to D.W
文摘Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of luteolin on nitric oxide （NO） formation in uric acid-stimulated Min6 cells using the Griess method. Next, we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor （NF）-κB. Western blotting assays were also performed to assess the effect of luteolin on the expression of MafA and inducible NO synthase （iNOS） in uric acid-treated cells. Finally, we evaluated the effect of luteolin on uric acidinduced inhibition of glucose-stimulated insulin secretion （GSIS） in Min6 cells and freshly isolated mouse pancreatic islets. We found that luteolin significantly inhibited uric acid-induced NO production, which was well correlated with reduced expression of iNOS mRNA and protein. Furthermore, decreased activity of NF-κB was implicated in inhibition by luteolin of increased iNOS expression induced by uric acid. Besides, luteolin significantly increased MafA expression in Min6 cells exposed to uric acid, which was reversed by overexpression of iNOS. Moreover, luteolin prevented uric acidinduced inhibition of GSIS in both Min6 cells and mouse islets. In conclusion, luteolin protects pancreatic β-cells from uric acid-induced dysfunction and may confer benefit on the protection of pancreatic β-cells in hyperuricemiaassociated diabetes.
基金supported by Major State Basic Research Program of China(Grant No.2013CB733801)
文摘Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown. Here, we first established a mini-stroke model by infusion of endothelin-1 （ET-1） into the dorsal hippo- campus or the lateral amygdala, and then investigated how these mini-infarcts affected brain functions associated with these regions. We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory, but not in learning process and recall of tone fear memory. In novel object task, ET-1 in the hippocampus also elimi- nated object identity memory. ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear. These findings suggest that ET-1- induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 30971380 and No. 31071026） and by the National Excellent Doctoral Dissertation of China.
文摘Background Low potassium dextran （LPD） solution can attenuate acute lung injury （ALl）. However, LPD solution for treating acute kidney injury secondary to ALl has not been reported. The present study was performed to examine the renoprotective effect of LPD solution in ALl induced by oleic acid （OA） in piglets. Methods Twelve animals that suffered an ALl induced by administration of OA into the right atrium were divided into two groups： the placebo group （n=6） pretreated with normal saline and the LPD group （n=6）, pretreated with LPD solution. LPD solution was injected intravenously at a dose of 12.5 ml/kg via the auricular vein 1 hour before OA injection. Results All animals survived the experiments with mild histopathological injury to the kidney. There were no significant differences in mean arterial pressure （MAP）, creatinin and renal damage scores between the two groups. Compared with the placebo group, the LPD group had better gas exchange parameters at most of the observation points （（347.0±12.6） mmHg vs. （284.3±11.3） mmHg at 6 hours after ALl, P 〈0.01）. After 6 hours of treatment with OA, the plasma concentrations of NGAL and intedeukin （IL）-6 in both groups increased dramatically compared to baseline （（6.0±0.6） and （2.50±0.08） folds in placebo group; and （2.5±0.5） and （1.40±0.05） folds in LPD group）, but the change of both parameters in the LPD group was significantly lower （P 〈0.01） than in the placebo group. And 6 hours after ALl the kidney tissue concentration of IL-6 in the LPD group （（165.7 ± 22.5） pg·m-1·g-1 protein） was significantly lower （P 〈0.01） than that in placebo group （（67.2± 25.3） pg·m-1·g-1 protein）. Conclusion These findings suggest that pretreatment with LPD solution via systemic administration might attenuate acute kidney injury and the cytokine response of IL-6 in the ALl piglet model induced by OA injection.
文摘A stereotypical presentation of a hero in a Hollywood action movie would lavishly brag about not only strong muscle but also a large statue(a.k.a.bone structure),ostensibly for an attractive image.Unknown to these movie producers is that the bone tissue does send a“sex-related”message,an endocrine message to be exact,to the male reproductive system.Maybe we shouldn’t blame Hollywood for their naivetéafter all;even in the scientific community,there is a long-held traditional belief that regards skeletal bone as merely a structural and supportive tissue.However,this view has been challenged by a series of recent studies.
