大黄素调节HMGB1/NF-κB信号通路对宫内炎症致早产大鼠脑损伤的保护作用  

Protective effect of emodin on brain injury induced by intrauterine inflammation in premature birth rats by regulating HMGB1/NF-κB signaling pathway

作　　者：喻龙凤 洪海柳 郎冰凝 黄赞怡 YU Longfeng;HONG Hailiu;LANG Bingning;HUANG Zanyi(Department of Obstetrics,Hainan Women and Children Medical Center,Haikou,Hainan 570100,China;Department of Gynecology,Hainan Women and Children Medical Center,Haikou,Hainan 570100,China)

机构地区：[1]海南省妇女儿童医学中心产科,海南海口570100 [2]海南省妇女儿童医学中心妇科,海南海口570100

出　　处：《中国优生与遗传杂志》2024年第2期281-289,共9页Chinese Journal of Birth Health & Heredity

基　　金：海南省卫生健康行业科研项目(22A200099)。

摘　　要：目的 探讨大黄素调节高迁移率族蛋白B1(HMGB1)/核转录因子-κB(NF-κB)信号通路对宫内炎症致早产大鼠脑损伤的保护作用机制。方法 制备孕鼠后腹腔内注射脂多糖建立宫内炎症致早产大鼠模型,随机分为模型组、大黄素低剂量(25 mg/kg)组、大黄素高剂量(50 mg/kg)组、空载质粒组、大黄素高剂量(50 mg/kg)+HMGB1过表达组,每组10只,另制备10只孕鼠腹腔内注射等剂量生理盐水作对照组,每组孕鼠所产的仔鼠随机选出10只,采用大黄素和质粒分组处理各组孕鼠和仔鼠后,检测各组孕鼠所生仔鼠活产数及出生体质量;H-E染色检测各组孕鼠子宫及胎盘病理形态变化;斜坡实验及圆筒实验检测各组仔鼠神经行为学能力;TUNEL染色检测各组仔鼠海马及脑皮质神经元凋亡;酶联免疫吸附法(ELISA)测定各组仔鼠脑组织与血清促炎因子环氧化酶-2(COX-2)、白细胞介素-6(IL-6)水平;蛋白免疫印迹法检测各组仔鼠脑组织HMGB1/NF-κB通路蛋白表达。结果 与对照组比较,模型组子宫及胎盘病理评分、转头所用时间、海马及脑皮质神经元凋亡率、脑组织与血清COX-2、IL-6水平、脑组织HMGB1蛋白表达及p-NF-κB p65/NF-κB p65升高(P<0.05),仔鼠活产数及出生体质量、碰触桶壁次数降低(P<0.05)。与模型组比较,大黄素低剂量组、大黄素高剂量组子宫及胎盘病理评分、转头所用时间、海马及脑皮质神经元凋亡率、脑组织与血清COX-2、IL-6水平、脑组织HMGB1蛋白表达及p-NF-κB p65/NF-κB p65均降低(P<0.05),仔鼠活产数及出生体质量、碰触桶壁次数均升高(P<0.05);HMGB1过表达可减弱大黄素高剂量对宫内炎症致早产孕鼠子宫、胎盘损伤和早产症状的改善作用,拮抗其对仔鼠的脑保护作用。结论 大黄素可通过抑制HMGB1/NF-κB信号激活而减少促炎因子产生,减轻孕鼠子宫、胎盘损伤,提升仔鼠神经行为能力并缓解其脑损伤。Objective To explore the protective mechanism of emodin on brain injury in premature birth rats induced by intrauterine inflammation by regulating high-mobility group protein B1(HMGB1)/nuclear transcription factor-κB(NF-κB)signaling pathway.Methods Pregnant rats were injected intraperitoneally with lipopolysaccharide to establish the model of premature birth induced by intrauterine inflammation.They were randomly divided into model group,low dose emodin(25 mg/kg) group,high dose emodin(50 mg/kg) group,empty plasmid group,and high dose emodin(50 mg/kg)+HMGB1overexpression group,with 10 rats in each group,10 pregnant rats were injected with an equal dose of physiological saline intraperitoneally as the control group,10 offspring rats of pregnant rats in each group were randomly selected,after treatment with emodin and plasmid,the number of live births and birth weight of offspring of pregnant rats in each group were measured.The pathological morphological changes of uterus and placenta were detected by H-E staining.The slope experiment and cylinder experiment were used to test the neuroethology ability of offspring rats in each group.TUNEL staining was used to detect neuronal apoptosis in the hippocampus and cerebral cortex of offspring rats in each group;enzyme linked immunosorbent assay(ELISA) was used to determine the levels of pro-inflammatory factor cyclooxygenase-2(COX-2) and interleukin-6(IL-6)in the brain tissue and serum of the offspring in each group.Western blot was used to detect the expression of HMGB1/NF-κB pathway proteins in the brain tissues of offspring rats in each group.Results Compared with the control group,the pathological scores of uterus and placenta,the time of turning head,the apoptosis rate of neurons in hippocampus and cerebral cortex,the levels of COX-2 and IL-6 in brain tissue and serum,the expression of HMGB1 protein in brain tissue,and p-NF-κB p65/NF-κB p65 in the model group increased(P<0.05),the number of live births,birth weight of offspring,and the number of times of touchi

关 键 词：大黄素 HMGB1/NF-κB 宫内炎症 早产 脑损伤 

分 类 号：R285.5[医药卫生—中药学]