We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation r...We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.展开更多
目的建立不同剂量双酚S(Bisphenol S,BPS)暴露动物实验模型,分析大鼠尿液中BPS内暴露水平的动态变化。方法通过灌胃给药建立对照组、1μg/kg低剂量组、100μg/kg中剂量组和10 mg/kg高剂量组Sprague Dawley(SD)大鼠暴露模型,使用超高效...目的建立不同剂量双酚S(Bisphenol S,BPS)暴露动物实验模型,分析大鼠尿液中BPS内暴露水平的动态变化。方法通过灌胃给药建立对照组、1μg/kg低剂量组、100μg/kg中剂量组和10 mg/kg高剂量组Sprague Dawley(SD)大鼠暴露模型,使用超高效液相色谱-串联质谱法(Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry,UPLC-MS/MS)内标法检测大鼠在连续6周暴露不同剂量BPS后其尿样中BPS含量的变化。结果目标物BPS在0.2~100μg/L的范围内呈良好线性关系,r^(2)≥0.998,方法检出限为0.01μg/L,定量限为0.03μg/L。对大鼠尿液的检测结果表明,随着暴露时间的增加,BPS在各剂量组大鼠体内的生物累积效应明显,尿液中BPS的内暴露水平在给药的6周中持续升高,且从给药后的第一周开始,尿液BPS含量的组间差异均有统计学意义(P<0.05)。结论本研究成功建立了不同剂量BPS暴露的SD大鼠动物实验模型,准确测定了大鼠连续6周尿液中双酚S的内暴露水平,为BPS毒理学剂量-效应关系研究提供参考。展开更多
基金supported by the National Natural Science Foundation of China,Nos.82271327(to ZW),82072535(to ZW),81873768(to ZW),and 82001253(to TL).
文摘We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.
文摘目的建立不同剂量双酚S(Bisphenol S,BPS)暴露动物实验模型,分析大鼠尿液中BPS内暴露水平的动态变化。方法通过灌胃给药建立对照组、1μg/kg低剂量组、100μg/kg中剂量组和10 mg/kg高剂量组Sprague Dawley(SD)大鼠暴露模型,使用超高效液相色谱-串联质谱法(Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry,UPLC-MS/MS)内标法检测大鼠在连续6周暴露不同剂量BPS后其尿样中BPS含量的变化。结果目标物BPS在0.2~100μg/L的范围内呈良好线性关系,r^(2)≥0.998,方法检出限为0.01μg/L,定量限为0.03μg/L。对大鼠尿液的检测结果表明,随着暴露时间的增加,BPS在各剂量组大鼠体内的生物累积效应明显,尿液中BPS的内暴露水平在给药的6周中持续升高,且从给药后的第一周开始,尿液BPS含量的组间差异均有统计学意义(P<0.05)。结论本研究成功建立了不同剂量BPS暴露的SD大鼠动物实验模型,准确测定了大鼠连续6周尿液中双酚S的内暴露水平,为BPS毒理学剂量-效应关系研究提供参考。
