郑州大学学报（医学版）2026，Vol.61Issue(2)：76-81,6.DOI:10.13705/j.issn.1671-6825.2025.03.091
基于TLR4/MyD88/NF-κB通路探讨肉豆蔻提取物对宫内炎症致早产大鼠脑损伤的影响
Effects of nutmeg extract on brain injury in premature rats induced by in-trauterine inflammation based on TLR4/MyD88/NF-κB pathway
摘要
Abstract
Aim:To investigate the effects of nutmeg extract on brain injury in premature rats induced by intrauterine inflammation based on the TLR4/MyD88/NF-κB pathway.Methods:A total of 60 pregnant SD rats were randomly divided into the normal group(n=12)and the modeling group(n=48)at a ratio of 1:4.A premature rat brain injury model in-duced by intrauterine inflammation was constructed by intraperitoneal injection of LPS.The 48 pregnant rats with successful modeling were randomly divided into 4 groups(12 per group):model group,low-dose nutmeg extract group,high-dose nut-meg extract group,and high-dose nutmeg extract+LPS(TLR4 agonist)group.Pregnant rats were continuously intervened for 2 days starting from the 17th day of gestation,and offspring rats were continuously intervened for 7 days after birth.Corre-sponding doses of normal saline,nutmeg extract(5,10 mg/kg)and LPS(0.1 mg/kg)were administered to the rats via in-traperitoneal injection,respectively.After the intervention,the survival number and body weight of offsprings produced by pregnant rats were measured.The neurobehavior of offspring rats was detected by the suspension test and inclined plane test.HE staining was applied to observe the pathological changes in the uterus,placenta from pregnant rats,and brain tissue from offspring rats.The expressions of ionized calcium-binding adapter molecule 1(Iba-1)and glial fibrillary acidic protein(GFAP)in brain tissue of offspring rats were detected by immunofluorescence staining.ELISA was applied to detect the levels of IL-1β,IL-6,and IL-8 in the brain tissue homogenate of offspring rats.The expressions of myelin basic protein(MBP)in brain tissue of offspring rats was detected by immunohistochemistry.Western blot was applied to detect the ex-pression levels of MBP and TLR4/MyD88/NF-κB signaling pathway related proteins in the brain tissue of offspring rats.Results:The survival number,body weight,and suspension test score of the offspring in the model group reduced compared with the normal group;the time taken for the head rotation in the inclined plane test,the expressions of Iba-1 and GFAP in the brain tissue of the offspring,the levels of IL-1β,IL-6,and IL-8 in the brain tissue homogenate of the offspring,the ex-pression of TLR4 and MyD88 proteins in the brain tissue,and the phosphorylation level of NF-κB p65 increased;the expres-sion of MBP in brain tissue of the offspring decreased(P<0.05).There was congestion in the blood vessels of the uterus and placenta tissues of pregnant rats,with disordered and unclear cell arrangement,and a large amount of neutrophil infiltra-tion;the arrangement of paraventricular white matter cells in the brain tissue of offspring rats was disorder and loose,with nerve fibers arranged in a network or strip like pattern,irregular,and a large number of inflammatory cells infiltrating.The changes in the above indexes of the low-dose and high-dose nutmeg extract groups were opposite(P<0.05),and the patho-logical damage to the uterus,placenta,and brain tissue of rats was reduced.LPS weakened the alleviating effects of nutmeg extract on brain injury in premature rats induced by intrauterine inflammation(P<0.05).Conclusion:Nutmeg extract may alleviate brain injury in premature rats induced by intrauterine inflammation by downregulating the TLR4/MyD88/NF-κB signaling pathway.关键词
TLR4/MyD88/NF-κB 通路/肉豆蔻/宫内炎症/早产/脑损伤/大鼠Key words
TLR4/MyD88/NF-κB pathway/nutmeg/intrauterine inflammation/premature/brain injury/rat分类
医药卫生引用本文复制引用
王晓芳,徐敏,邓海云,李若佳,王梅霞,刘洋..基于TLR4/MyD88/NF-κB通路探讨肉豆蔻提取物对宫内炎症致早产大鼠脑损伤的影响[J].郑州大学学报（医学版）,2026,61(2):76-81,6.基金项目
河北省卫生和计划生育委员会科研基金项目(20241709) （20241709）
