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副干酪乳酪杆菌CCFM1317激活Keap1/Nrf2通路缓解小鼠阴道加德纳菌感染

Lacticaseibacillus paracasei CCFM1317 alleviates Gardnerella vaginalis infection in mice by activating expression of Keap1/Nrf2 pathway
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摘要 乳杆菌有助于调节机体抗氧化信号通路,上调抗氧化酶类的表达缓解氧化损伤。该研究旨在探讨特定益生菌对宿主抗氧化能力的提升,及其在调节阴道加德纳菌(Gardnerella vaginalis,GV)感染造成的氧化应激中的作用。通过建立炎症模型和筛选具有抗氧化潜力的乳杆菌,该研究采用1.25μg/mL的脂多糖处理VK2/E6E7细胞24 h,使用CCK-8法确定具有抗氧化潜力的乳杆菌。在动物实验中,采用颈部皮下注射5 mg/mL戊酸雌二醇和阴道注射20μL 1010 CFU/mL的GV建立小鼠感染模型,随后连续10 d灌胃100μL 109 CFU/mL的乳杆菌菌悬液。实验结束后,对不同组别小鼠阴道进行GV载量检测、病理组织切片观察以及抗氧化信号通路Kelch-like ECH-associated protein 1(Keap1)/Nuclear factor erythroid 2-related factor 2(Nrf2)表达检测。研究结果显示,副干酪乳酪杆菌CCFM1317在体外试验中可显著上调细胞活力至109.0%。在动物试验中,口服CCFM1317后,GV载量下降了40.6%,阴道组织的病理切片结果也显示良好表征。进一步地,检测阴道组织Keap1/Nrf2信号通路表达情况,发现CCFM1317可使Keap1 mRNA水平表达显著降低48.6%,Nrf2 mRNA水平表达显著上调(P<0.0001),同时Nrf2含量上升了1.9倍。综上,该研究筛选的副干酪乳酪杆菌CCFM1317具有增强阴道抗氧化能力的特性,能够帮助机体缓解氧化应激。 Lactobacillus species have been recognized for their potential to modulate the antioxidant signalling pathway,thereby upregulating the expression of antioxidant enzymes and mitigating oxidative damage.The study was undertaken to explore the enhancement of host antioxidant capacity by specific probiotics and their role in modulating oxidative stress induced by Gardnerella vaginalis(GV)infection.An inflammatory model was developed by treating VK2/E6E7 cells with 1.25μg/mL lipopolysaccharide(LPS)for 24 hours.The Cell Counting Kit-8(CCK-8)assay was then employed to identify Lactobacilli with antioxidant potential.An animal infection model was established via subcutaneous injection of 5 mg/mL estradiol valerate in the neck and vaginal injection of 20μL containing 1010 CFU/mL GV solution.Subsequently,a 100μL Lactobacillus suspension at a concentration of 109 CFU/mL was gavaged to the mice daily for 10 days.At the end of the experiment,GV load,histopathological assessments,and expression levels of the antioxidant signalling pathway proteins Kelch-like ECH-associated protein 1(Keap1)and nuclear factor erythroid 2-related factor 2(Nrf2)in vaginal tissue of various group were evaluated.Results showed that Lactobacillus paracasei CCFM1317 significantly enhanced cell viability to 109.0% in vitro.In the animal trial,oral administration of CCFM1317 led to a reduction in the GV load by 40.6%.Histopathological examination of vaginal tissue revealed epithelial continuity restoration and a decrease in the severity of inflammatory cell infiltration.Furthermore,investigation of Keap1/Nrf2 signalling pathway expression in vaginal tissue revealed that CCFM1317 markedly decreased Keap1 mRNA expression by 48.6% and significantly increased Nrf2 mRNA expression(P<0.0001),with a 1.9-fold increase in Nrf2 content.These findings demonstrated that L.paracasei CCFM1317 possesses characteristics that enhance vaginal antioxidant defenses and may potentially alleviate oxidative stress-related symptoms during vaginitis.
作者 林如梦 黄小艳 崔树茂 毛丙永 唐鑫 赵建新 张秋香 LIN Rumeng;HUANG Xiaoyan;CUI Shumao;MAO Bingyong;TANG Xin;ZHAO Jianxin;ZHANG Qiuxiang(School of Food Science and Technology,Jiangnan University,Wuxi 214122,China)
出处 《食品与发酵工业》 北大核心 2025年第3期21-27,共7页 Food and Fermentation Industries
基金 国家自然科学基金项目(32372300)。
关键词 乳杆菌 阴道加德纳菌 氧化应激 Keap1/Nrf2信号通路 VK2/E6E7 Lactobacillus Gardnerella vaginalis oxidative stress Keap1/Nrf2 signalling pathway VK2/E6E7
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