遵义医科大学学报2026，Vol.49Issue(5)：493-501,9.
重组DHCR7抑制NF-κB通路改善脓毒症相关性脑病的作用机制
Mechanism of recombinant DHCR7 inhibiting NF-κB pathway to improve sep-sis-related encephalopathy
摘要
Abstract
Objective To investigate the neuroprotective effects and potential mechanisms of exogenous admin-istration of 7-dehydrocholesterol reductase(DHCR7)recombinant protein on sepsis-associated encephalopathy(SAE)induced by lipopolysaccharide(LPS)in mice.Methods C57BL/6J mice were randomly divided into four groups:sham operation group(Sham),SAE model group(LPS),DHCR7 recombinant protein treatment group alone(DHCR7),and SAE model combined with DHCR7 treatment group(LPS+DHCR7).SAE mod-el was established by intraperitoneal injection of LPS(10 mg/kg),followed by intracranial injection of DHCR7 recombinant protein(0.25 μg/μL,2 μL)2 hours after model establishment.Twenty-four hours after admin-istration,the general state of mice in each group was assessed,and brain tissues were collected for HE staining to observe pathological changes.RT-qPCR was used to detect the mRNA expression levels of inflammatory fac-tors(IL-1β,IL-6,TNF-α,LCN2,NF-κB,IκB-α,NOX-2),apoptosis gene caspase-3,and DHCR7.ELISA was used to measure the levels of S100β in brain tissue.Biochemical methods were used to detect the total cholesterol(TC)level in brain tissues.Western blotting was used to verify the changes in related protein expression,in order to explore the possible mechanism by which DHCR7 regulates neuroinflammation to im-prove SAE.Results Mice in the LPS group exhibited obvious signs of infection(listlessness,trembling,pilo-erection,increased eye and nasal secretions,and sticky feces).Significant inflammatory cell infiltration and neuronal shrinkage were observed in brain tissue stained with HE.Compared to the Sham group,the LPS group showed significantly elevated mRNA and protein expression levels of IL-1β,IL-6,TNF-α,LCN2,NF-κB,IκB-α,NOX-2,and caspase-3 in brain tissue,while the expression level of DHCR7 decreased.TC con-tent in brain tissue significantly decreased.After exogenous supplementation with DHCR7 recombinant protein,the aforementioned abnormal changes were alleviated to varying degrees.Conclusion Exogenous DHCR7 re-combinant protein alleviates neuroinflammation in SAE mice by inhibiting the NF-κB pathway through upregula-tion of brain cholesterol levels.关键词
脂多糖/脓毒症相关性脑病/神经炎症/7-脱氢胆固醇还原酶Key words
lipopolysaccharide/sepsis-associated encephalopathy/neuroinflammation/7-dehydrocholesterol reductase分类
医药卫生引用本文复制引用
丁莉,罗遵伟,王兵,沈沛,游安兴,杜娟,薛娇,蒲清瑚,周满红..重组DHCR7抑制NF-κB通路改善脓毒症相关性脑病的作用机制[J].遵义医科大学学报,2026,49(5):493-501,9.基金项目
贵州省卫生健康委科技基金项目(NO:GZWJKJXM0035) （NO:GZWJKJXM0035）
遵义市科技计划项目[NO:遵市科合HZ字(2024)439]. （2024）
