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
Background In vitro fertilization （IVF） researches have suggested that cystathionine β synthase （CBS） is involved in oocyte development. However, little is known about the regional and cellular expression pattern...Background In vitro fertilization （IVF） researches have suggested that cystathionine β synthase （CBS） is involved in oocyte development. However, little is known about the regional and cellular expression patterns of CBS in the ovary. The purpose of this study was to analyze the localization of CBS in mice ovaries and to investigate the expression profile during follicular development. Methods We used in situ hybridization and immunohistochemical analysis to determine CBS expression in the ovaries of female Balb/c mice. Then the follicles were collected from F1 （C57BL×Balb/c） mice and cultured in vitro. With the method of semi-quantitative RT-PCR, we also investigated the expression profile of CBS during follicular development. Results CBS was absent in the oocytes, although it was ubiquitously expressed in the ovary with the strongest expression in follicular cells at all stages. In late antral follicles, CBS expression was markedly higher in granulosa cells located close to the antrum and in cumulus cells around the oocyte. The semi-quantitative RT-PCR showed that CBS mRNA was detected in follicles at all stages in vitro. In cumulus-oocyte complexes superovulated, CBS expression also increased rapidly. Conclusions CBS was located mainly in the follicular cells in the ovaries. The level of CBS expression is high in follicles during folliculogenesis in mice. Differences in the CBS expression profile between oocyte and follicular cells suggest a role for CBS as a mediator in interactions between oocyte and granulosa cells.展开更多
目的研究胱硫醚β合酶(CBS)基因T833C突变对中青年缺血性卒中/TIA再发的影响。方法对中青年缺血性卒中/TIA患者,采用高压液相色谱法测定血浆总同型半胱氨酸(tHcy)水平,采用扩增阻滞突变体系法(PCR-ARMS)技术检测CBS T833C基因型,跟踪观...目的研究胱硫醚β合酶(CBS)基因T833C突变对中青年缺血性卒中/TIA再发的影响。方法对中青年缺血性卒中/TIA患者,采用高压液相色谱法测定血浆总同型半胱氨酸(tHcy)水平,采用扩增阻滞突变体系法(PCR-ARMS)技术检测CBS T833C基因型,跟踪观察5年内中青年缺血性卒中/TIA的后发事件。结果再发组CBS基因C/C、C/T型和C等位基因频率分别高于非再发组(P<0.05),两组不同基因型血浆tHcy水平比较,再发组中C/C型分别高于C/T和T/T型,C/T高于T/T型(P<0.01);非再发组中C/C和C/T型分别高于T/T型(P<0.01);相同C/T型血浆tHcy水平比较,再发组高于非再发组(P<0.01)。结论 CBS T833C基因突变可能是引起高同型半胱氨酸血症(Hhcy)间接导致中青年缺血性卒中/TIA患者再发的重要遗传危险因素。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.
基金This research was supported by a grant from the Special Funds for Major State Basic Research of China (No.2001CB510303).
文摘Background In vitro fertilization （IVF） researches have suggested that cystathionine β synthase （CBS） is involved in oocyte development. However, little is known about the regional and cellular expression patterns of CBS in the ovary. The purpose of this study was to analyze the localization of CBS in mice ovaries and to investigate the expression profile during follicular development. Methods We used in situ hybridization and immunohistochemical analysis to determine CBS expression in the ovaries of female Balb/c mice. Then the follicles were collected from F1 （C57BL×Balb/c） mice and cultured in vitro. With the method of semi-quantitative RT-PCR, we also investigated the expression profile of CBS during follicular development. Results CBS was absent in the oocytes, although it was ubiquitously expressed in the ovary with the strongest expression in follicular cells at all stages. In late antral follicles, CBS expression was markedly higher in granulosa cells located close to the antrum and in cumulus cells around the oocyte. The semi-quantitative RT-PCR showed that CBS mRNA was detected in follicles at all stages in vitro. In cumulus-oocyte complexes superovulated, CBS expression also increased rapidly. Conclusions CBS was located mainly in the follicular cells in the ovaries. The level of CBS expression is high in follicles during folliculogenesis in mice. Differences in the CBS expression profile between oocyte and follicular cells suggest a role for CBS as a mediator in interactions between oocyte and granulosa cells.
文摘目的研究胱硫醚β合酶(CBS)基因T833C突变对中青年缺血性卒中/TIA再发的影响。方法对中青年缺血性卒中/TIA患者,采用高压液相色谱法测定血浆总同型半胱氨酸(tHcy)水平,采用扩增阻滞突变体系法(PCR-ARMS)技术检测CBS T833C基因型,跟踪观察5年内中青年缺血性卒中/TIA的后发事件。结果再发组CBS基因C/C、C/T型和C等位基因频率分别高于非再发组(P<0.05),两组不同基因型血浆tHcy水平比较,再发组中C/C型分别高于C/T和T/T型,C/T高于T/T型(P<0.01);非再发组中C/C和C/T型分别高于T/T型(P<0.01);相同C/T型血浆tHcy水平比较,再发组高于非再发组(P<0.01)。结论 CBS T833C基因突变可能是引起高同型半胱氨酸血症(Hhcy)间接导致中青年缺血性卒中/TIA患者再发的重要遗传危险因素。
