The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

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.

血清LDH、CK-MB、CK及cTnI在新生儿缺血缺氧性脑病中的变化和探讨

目的:探讨LDH、CK-MB、CK及cTnI含量在新生儿缺血缺氧性脑病中的变化特点。方法:72例不同时期患儿中均测定血清LDH、CK-MB、CK及cTnI含量的变化,所得的数据采用统计学处理。结果:患儿血清中LDH、CK-MB、CK及cTnI含量与对照组比较,均在急性期有明显的升高,其中LDH、CK-MB、CK表现明显P<0.01,cTnI与对照组间比较变化差异不明显,P<0.05。轻、重度(HIE)患儿在急性期和恢复期有明显的差异LDHP<0.01、CK-MB、CKP<0.05,而cTnI则无明显统计学意义P>0.05。结论:不同时期的新生儿缺血缺氧性脑病中的血清LDH、CK-MB、CK及cTnI含量的测定对临床很有意义,可帮助确定新生儿缺血缺氧性后脑组织损伤的严重程度和预后判断。