Normal tension glaucoma(NTG)is a multifactorial optic neuropathy characterized by normal intraocular pressure,progressive retinal ganglion cell(RGC)death,and glaucomatous visual field loss.Recent studies have describe...Normal tension glaucoma(NTG)is a multifactorial optic neuropathy characterized by normal intraocular pressure,progressive retinal ganglion cell(RGC)death,and glaucomatous visual field loss.Recent studies have described the mechanisms underlying the pathogenesis of NTG.In addition to controlling intraocular pressure,neuroprotection and reduction of RGC degeneration may be beneficial therapies for NTG.In this review,we summarized the main regulatory mechanisms of RGC death in NTG,including autophagy,glutamate neurotoxicity,oxidative stress,neuroinflammation,immunity,and vasoconstriction.Autophagy can be induced by retinal hypoxia and axonal damage.In this process,ischemia can cause mutations of optineurin and activate the nuclear factor-kappa B pathway.Glutamate neurotoxicity is induced by the over-stimulation of N-methyl-D-aspartate membrane receptors by glutamate,which occurs in RGCs and induces progressive glaucomatous optic neuropathy.Oxidative stress also participates in NTG-related glaucomatous optic neuropathy.It impairs the mitochondrial and DNA function of RGCs through the apoptosis signal-regulating kinase-JUN N-terminal kinase pathway.Moreover,it increases inflammation and the immune response of RGCs.Endothelin 1 causes endothelial dysfunction and impairment of ocular blood flow,promoting vasospasm and glaucomatous optic neuropathy,as a result of NTG.In conclusion,we discussed research progress on potential options for the protection of RGCs,including TANK binding kinase 1 inhibitors regulating autophagy,N-methyl-D-aspartate receptor antagonists inhibiting glutamate toxicity,ASK1 inhibitors regulating mitochondrial function,and antioxidants inhibiting oxidative stress.In NTG,RGC death is regulated by a network of mechanisms,while various potential targets protect RGCs.Collectively,these findings provide insight into the pathogenesis of NTG and potential therapeutic strategies.展开更多
A microwave-assisted solid phase synthesis for endothelin 1 is presented.Reduced endothelin 1 was synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy.The who...A microwave-assisted solid phase synthesis for endothelin 1 is presented.Reduced endothelin 1 was synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy.The whole peptide was cleaved from the resin and two disulphide bridges were formed under air oxidation at room temperature.The purity and efficiency of synthesizing the peptide is much higher than other methods used before.展开更多
To investigate the effect of neutrophil activation on pathogenesis of pre eclampsia, neutrophil activation was examined by using flow cytometry to assess the CD11b expression and the levels of plasma endothelin 1 (E...To investigate the effect of neutrophil activation on pathogenesis of pre eclampsia, neutrophil activation was examined by using flow cytometry to assess the CD11b expression and the levels of plasma endothelin 1 (ET 1) and serum NO - 2 were also measured by using non equilibrium radioimmunoassay and by Griess assay in 29 pregnant women with pre eclampsia and 31 normal pregnant women at third trimester. The expression of neutrophil CD11b was significantly elevated in women with pre eclampsia as compared with that of normal pregnant women at third trimester. The mean fluorescence index of CD11b was 438.38±179.91 and 326.97±170.14 respectively ( P < 0.05). The plasma ET 1 level and serum NO 2 concentration in pre eclampsic women (63.69±48.33 pg/ml and 20.03±4.77 μmol/L, respectively) were both significantly increased as compared with those in the normal pregnancy women (29.98±20.25 pg/ml and 15.47±5.47 μmol/L, respectively, P <0.01). The neutrophil CD11b expression was significantly elevated in pre eclampsia. The increased neutrophil activation may cause the damage of vascular endothelium and result in NO release compensatory increase in endothelial cells, suggesting that the neutrophil activation may play a key role in pathogenesis of pre eclampsia.展开更多
The present study was designed to determine the relationship between changes of plasma endothelin 1 concentrations and development of colonic obstruction in sleep.Colons were bound in three sheep with sterilized plas...The present study was designed to determine the relationship between changes of plasma endothelin 1 concentrations and development of colonic obstruction in sleep.Colons were bound in three sheep with sterilized plastic tubes to make pathological model of colonic obstruction.Samples were collected before and after modeling operation on both controls and models.Endothelin 1 concentrations were measured by radioimmunoassay.Plasma ET llevels decreased continually after the modeling operation in the models,it dropped from a basal value of 60 93±18 66 to 34 11±8 22 and 33 54±11 12 pg/mL(P<0 05) on the 3rd and 5 th day,respectively,which were also lower than controls 64 16±12 93 pg/mL(P<0 05).It suggests that colonic obstruction may induce a decrease in plasma endothelin 1 concentrations in sleep.展开更多
Objective To investigate the influence of captoprial and SNP on the release of ET -1 in cultured VSMC of rats. Methods Measurement of endothelin - 1 levels by radioimmljnoassay in various concentrations of captopril a...Objective To investigate the influence of captoprial and SNP on the release of ET -1 in cultured VSMC of rats. Methods Measurement of endothelin - 1 levels by radioimmljnoassay in various concentrations of captopril and/or sodium nitroprusside in cultured vascular smooth muscle cell (VSMC) of rats. Results Both captopril and SNP could reduce the high ET - 1 levels of VSMC which were caused by Ang Ⅱ. There was a linear relationship between Ang Ⅱlevels and ET -1 production ( r = 0. 760, P <0. 001 ) . Conclusion Endothelin - 1 may accelerate the formation and development of atherosclerosis through inhibiting endogenous NO production by VSMC. ACEI or NO inhibition of ET -1 release could reduce atherosclerosis formation.展开更多
基金supported in part by the Technology Foundation of Tianjin Eye Hospital of China, No. YKQN1911 (to WCS)Tianjin Health Science and Technology Project, No. TJWJ2021QN071 (to WCS)Translational Medicine Research Project of State Key Laboratory of Experimental Hematology of China, No. Z21-11 (to BQH)
文摘Normal tension glaucoma(NTG)is a multifactorial optic neuropathy characterized by normal intraocular pressure,progressive retinal ganglion cell(RGC)death,and glaucomatous visual field loss.Recent studies have described the mechanisms underlying the pathogenesis of NTG.In addition to controlling intraocular pressure,neuroprotection and reduction of RGC degeneration may be beneficial therapies for NTG.In this review,we summarized the main regulatory mechanisms of RGC death in NTG,including autophagy,glutamate neurotoxicity,oxidative stress,neuroinflammation,immunity,and vasoconstriction.Autophagy can be induced by retinal hypoxia and axonal damage.In this process,ischemia can cause mutations of optineurin and activate the nuclear factor-kappa B pathway.Glutamate neurotoxicity is induced by the over-stimulation of N-methyl-D-aspartate membrane receptors by glutamate,which occurs in RGCs and induces progressive glaucomatous optic neuropathy.Oxidative stress also participates in NTG-related glaucomatous optic neuropathy.It impairs the mitochondrial and DNA function of RGCs through the apoptosis signal-regulating kinase-JUN N-terminal kinase pathway.Moreover,it increases inflammation and the immune response of RGCs.Endothelin 1 causes endothelial dysfunction and impairment of ocular blood flow,promoting vasospasm and glaucomatous optic neuropathy,as a result of NTG.In conclusion,we discussed research progress on potential options for the protection of RGCs,including TANK binding kinase 1 inhibitors regulating autophagy,N-methyl-D-aspartate receptor antagonists inhibiting glutamate toxicity,ASK1 inhibitors regulating mitochondrial function,and antioxidants inhibiting oxidative stress.In NTG,RGC death is regulated by a network of mechanisms,while various potential targets protect RGCs.Collectively,these findings provide insight into the pathogenesis of NTG and potential therapeutic strategies.
基金supported by the key project of Chinese Ministry of Education(No.109086)
文摘A microwave-assisted solid phase synthesis for endothelin 1 is presented.Reduced endothelin 1 was synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy.The whole peptide was cleaved from the resin and two disulphide bridges were formed under air oxidation at room temperature.The purity and efficiency of synthesizing the peptide is much higher than other methods used before.
文摘To investigate the effect of neutrophil activation on pathogenesis of pre eclampsia, neutrophil activation was examined by using flow cytometry to assess the CD11b expression and the levels of plasma endothelin 1 (ET 1) and serum NO - 2 were also measured by using non equilibrium radioimmunoassay and by Griess assay in 29 pregnant women with pre eclampsia and 31 normal pregnant women at third trimester. The expression of neutrophil CD11b was significantly elevated in women with pre eclampsia as compared with that of normal pregnant women at third trimester. The mean fluorescence index of CD11b was 438.38±179.91 and 326.97±170.14 respectively ( P < 0.05). The plasma ET 1 level and serum NO 2 concentration in pre eclampsic women (63.69±48.33 pg/ml and 20.03±4.77 μmol/L, respectively) were both significantly increased as compared with those in the normal pregnancy women (29.98±20.25 pg/ml and 15.47±5.47 μmol/L, respectively, P <0.01). The neutrophil CD11b expression was significantly elevated in pre eclampsia. The increased neutrophil activation may cause the damage of vascular endothelium and result in NO release compensatory increase in endothelial cells, suggesting that the neutrophil activation may play a key role in pathogenesis of pre eclampsia.
文摘The present study was designed to determine the relationship between changes of plasma endothelin 1 concentrations and development of colonic obstruction in sleep.Colons were bound in three sheep with sterilized plastic tubes to make pathological model of colonic obstruction.Samples were collected before and after modeling operation on both controls and models.Endothelin 1 concentrations were measured by radioimmunoassay.Plasma ET llevels decreased continually after the modeling operation in the models,it dropped from a basal value of 60 93±18 66 to 34 11±8 22 and 33 54±11 12 pg/mL(P<0 05) on the 3rd and 5 th day,respectively,which were also lower than controls 64 16±12 93 pg/mL(P<0 05).It suggests that colonic obstruction may induce a decrease in plasma endothelin 1 concentrations in sleep.
文摘Objective To investigate the influence of captoprial and SNP on the release of ET -1 in cultured VSMC of rats. Methods Measurement of endothelin - 1 levels by radioimmljnoassay in various concentrations of captopril and/or sodium nitroprusside in cultured vascular smooth muscle cell (VSMC) of rats. Results Both captopril and SNP could reduce the high ET - 1 levels of VSMC which were caused by Ang Ⅱ. There was a linear relationship between Ang Ⅱlevels and ET -1 production ( r = 0. 760, P <0. 001 ) . Conclusion Endothelin - 1 may accelerate the formation and development of atherosclerosis through inhibiting endogenous NO production by VSMC. ACEI or NO inhibition of ET -1 release could reduce atherosclerosis formation.
