摘要
目的探究大黄素对感染性早产大鼠的改善作用及机制。方法构建感染性早产大鼠模型,将其分成模型组、大黄素组(60 mg/kg,灌胃)、核因子κB(NF-κB)抑制蛋白激酶(IKK)激活组(2μg pcDNA3.1-IKK重组质粒,尾静脉注射)、大黄素+IKK激活组(灌胃60 mg/kg大黄素+尾静脉注射2μg pcDNA3.1-IKK重组质粒),每组14只。另取14只受孕雌鼠作为对照组。各组大鼠给予相应药物干预7 d。检测大鼠子宫肌条肌张力和血清中炎症指标[白细胞介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)]和氧化应激指标[超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)]水平;观察大鼠子宫组织病理学形态变化;检测大鼠子宫组织中NOD样受体蛋白3(NLRP3)、剪切型胱天蛋白酶1(cleaved-caspase-1)和IKK/NF-κB抑制蛋白(IκB)/NF-κB信号通路相关蛋白表达水平。结果与对照组相比,模型组大鼠子宫平滑肌出现了大量炎症细胞浸润,细胞分布不规则;子宫肌条肌张力和血清中IL-1β、IL-6、TNF-α、MDA水平以及子宫组织中NLRP3、cleaved-caspase-1、IKK、IκB、NF-κB p65蛋白表达水平均显著升高(P<0.05),血清中SOD、CAT水平均显著降低(P<0.05)。与模型组相比,大黄素组大鼠子宫平滑肌层炎症细胞浸润现象减轻,各定量指标均明显改善(P<0.05);IKK激活组大鼠子宫平滑肌层炎症细胞浸润现象加重,各定量指标均进一步恶化(P<0.05)。激活IKK可明显减弱大黄素对感染性早产大鼠上述指标的改善作用(P<0.05)。结论大黄素可能通过抑制IKK/IκB/NF-κB信号通路活性,减轻炎症反应和氧化应激,从而改善感染性早产大鼠子宫平滑肌收缩。
OBJECTIVE To explore the ameliorative effect and mechanism of emodin on infectious preterm rats.METHODS The infectious preterm rat model was established and divided into model group,emodin group(60 mg/kg,i.g.),IKK activation group(2μg pcDNA3.1-IKK recombinant plasmid via tail vein),emodin+IKK activation group(i.g.60 mg/kg emodin+2μg pcDNA3.1-IKK recombinant plasmid via tail vein),with 14 rats in each group.Another 14 pregnant female rats were set up as control group.Each group received corresponding intervention for 7 days.The muscle tension of the uterine muscle strip,and the indicator levels of serum inflammation[interleukin 1β(IL-1β),IL-6,tumor necrosis factorα(TNF-α)]and oxidative stress[superoxide dismutase(SOD),malondialdehyde(MDA),catalase(CAT)]were detected;the pathological morphological changes of uterine tissue in rats were observed;the protein expressions of NOD-like receptor protein 3(NLRP3),cleaved-caspase-1 and IKK/IκB/NF-κB signaling pathway were detected.RESULTS Compared with control group,a large number of inflammatory cells infiltrated into the smooth muscle layer of uterus in model group with irregular cell distribution;the uterine muscle strip muscle tone,serum levels of IL-1β,IL-6,TNF-αand MDA,protein expressions of NLRP3,cleaved-caspase-1,IKK,IκB and NF-κB p65 in uterine tissue were significantly increased in model group,and the serum levels of SOD and CAT were significantly decreased(P<0.05).Compared with the model group,the infiltration of inflammatory cells in the uterine smooth muscle layer was reduced in the emodin group,and all quantitative indexes were significantly improved(P<0.05);the infiltration of inflammatory cells in the uterine smooth muscle layer was increased in IKK activation group,and all quantitative indexes further deteriorated(P<0.05).Activation of IKK could significantly reduce the improvement effect of emodin on the above indexes in infectious preterm rats(P<0.05).CONCLUSIONS Emodin can relieve inflammation and oxidative stress in infectious preterm rats by inhibiting the IKK/IκB/NF-κB signaling pathway,thus improving uterine smooth muscle contraction.
作者
曹定娅
武晓娟
付婷婷
宋兵
CAO Dingya;WU Xiaojuan;FU Tingting;SONG Bing(Dept.of Prenatal Diagnosis,the Third Hospital Affiliated to Guangzhou Medical University,Guangzhou 510150,China;Guangdong Provincial Key Laboratory of Obstetrics Major Diseases,Guangzhou 510150,China;Dept.of Obstetrics and Gynecology,the Third Hospital Affiliated to Guangzhou Medical University,Guangzhou 510150,China)
出处
《中国药房》
CAS
北大核心
2024年第21期2629-2633,共5页
China Pharmacy
基金
广州市卫生健康科技项目(No.20221A011088)。
