Sirtuin 2(SIRT2)inhibition or Sirt2 knocko ut in animal models protects against the development of neurodegenerative diseases and cerebral ischemia.However,the role of SIRT2 in traumatic brain injury(TBI)remains uncle...Sirtuin 2(SIRT2)inhibition or Sirt2 knocko ut in animal models protects against the development of neurodegenerative diseases and cerebral ischemia.However,the role of SIRT2 in traumatic brain injury(TBI)remains unclear.In this study,we found that knockout of Sirt2 in a mouse model of TBI reduced brain edema,attenuated dis ruption of the blood-brain barrie r,decreased expression of the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome,reduced the activity of the effector caspase-1,reduced neuroinflammation and neuronal pyroptosis,and improved neurological function.Knoc kout of Sirt2 in a mechanical stretch injury cell model in vitro also decreased expression of the NLRP3 inflammasome and pyroptosis.Our findings suggest that knockout of Sirt2 is neuro protective against TBI;therefore.Sirt2 could be a novel to rget for TBI treatment.展开更多
AIM： To observe the attenuation of ethanol extract of Herba Scutellaria barbata （SE） against diabetic retinopathy （DR） and its engaged mechanism. METHODS： C57BL/6J mice were intraperitoneally injected with stre...AIM： To observe the attenuation of ethanol extract of Herba Scutellaria barbata （SE） against diabetic retinopathy （DR） and its engaged mechanism. METHODS： C57BL/6J mice were intraperitoneally injected with streptozotocin （STZ, 55 mg/kg） for 5 consecutive days to induce diabetes, The diabetic mice were orally given with SE （100, 200 mg/kg） for lmo at lmo after STZ injection. Blood-retinal barrier （BRB） breakdown was detected by using Evans blue permeation assay. Real-time polymerase chain reaction （RT-PCR）, Western blot and immunofiuorescence staining were used to detect mRNA and protein expression. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum contents of tumor necrosis factor-e （TNF-a） and interleukin （IL）-II. RESULTS： SE （100, 200 mg/kg） reversed the breakdown of BRB in STZ-induced diabetic mice. The decreased expression of retinal claudin-1 and claudin-19, which are both tight junction （T J） proteins, was reversed by SE. SE decreased the increased serum contents and retinal mRNA expression of TNF-a and IL-113. SE also decreased the increased retinal expression of intercellular cell adhesion molecule-1 （ICAM-1）. SE reduced the increased phosphorylation of nuclear factor kappa B （NFKB） p65 and its subsequent nuclear translocation in retinas from STZ- induced diabetic mice. Results of Western blot and retinal immunofluorescence staining of ionized calcium-binding adapter molecule 1 （Ibal） demonstrated that SE abrogated the activation of microglia cells in STZ-induced diabetic mice. CONCLUSION： SE attenuates the development of DR by inhibiting retinal inflammation and restoring the decreased expression of TJ proteins including claudin-1 and claudin-19.展开更多
基金supported by the National Nature Science Foundation of China,Nos.81671207 and 81974189(both to HLT)。
文摘Sirtuin 2(SIRT2)inhibition or Sirt2 knocko ut in animal models protects against the development of neurodegenerative diseases and cerebral ischemia.However,the role of SIRT2 in traumatic brain injury(TBI)remains unclear.In this study,we found that knockout of Sirt2 in a mouse model of TBI reduced brain edema,attenuated dis ruption of the blood-brain barrie r,decreased expression of the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome,reduced the activity of the effector caspase-1,reduced neuroinflammation and neuronal pyroptosis,and improved neurological function.Knoc kout of Sirt2 in a mechanical stretch injury cell model in vitro also decreased expression of the NLRP3 inflammasome and pyroptosis.Our findings suggest that knockout of Sirt2 is neuro protective against TBI;therefore.Sirt2 could be a novel to rget for TBI treatment.
基金Supported by the National Natural Science Foundation of China(No.81173517No.81322053)
文摘AIM： To observe the attenuation of ethanol extract of Herba Scutellaria barbata （SE） against diabetic retinopathy （DR） and its engaged mechanism. METHODS： C57BL/6J mice were intraperitoneally injected with streptozotocin （STZ, 55 mg/kg） for 5 consecutive days to induce diabetes, The diabetic mice were orally given with SE （100, 200 mg/kg） for lmo at lmo after STZ injection. Blood-retinal barrier （BRB） breakdown was detected by using Evans blue permeation assay. Real-time polymerase chain reaction （RT-PCR）, Western blot and immunofiuorescence staining were used to detect mRNA and protein expression. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum contents of tumor necrosis factor-e （TNF-a） and interleukin （IL）-II. RESULTS： SE （100, 200 mg/kg） reversed the breakdown of BRB in STZ-induced diabetic mice. The decreased expression of retinal claudin-1 and claudin-19, which are both tight junction （T J） proteins, was reversed by SE. SE decreased the increased serum contents and retinal mRNA expression of TNF-a and IL-113. SE also decreased the increased retinal expression of intercellular cell adhesion molecule-1 （ICAM-1）. SE reduced the increased phosphorylation of nuclear factor kappa B （NFKB） p65 and its subsequent nuclear translocation in retinas from STZ- induced diabetic mice. Results of Western blot and retinal immunofluorescence staining of ionized calcium-binding adapter molecule 1 （Ibal） demonstrated that SE abrogated the activation of microglia cells in STZ-induced diabetic mice. CONCLUSION： SE attenuates the development of DR by inhibiting retinal inflammation and restoring the decreased expression of TJ proteins including claudin-1 and claudin-19.
