摘要
目的:观察雷公藤内酯酮对急性单核细胞白血病小鼠的抗肿瘤作用,并基于抗炎和调控肠道菌群探讨其作用机制。方法:BALB/c裸雌性小鼠20只,皮下注射急性单核细胞白血病细胞株(U937)建立白血病模型,根据肿瘤体积随机分为2组,每组8只。雷公藤内酯酮组按10 mg/kg剂量灌胃给药,对照组灌胃给予等体积生理盐水1次/d。连续给予2周后,处死小鼠收集样本。苏木精-伊红(HE)染色观察瘤体坏死情况,免疫组织化学(IHC)检测肿瘤组织中磷酸化核因子κB抑制蛋白(p-IκB)、磷酸化κB抑制因子激酶(p-IKK)、磷酸化核因子κB(p-NF-κB)蛋白表达情况,酶联免疫吸附试验法(ELISA)检测血清中炎症介质含量,16S核糖体核糖核酸(16S rRNA)测序法分析小鼠肠道菌群的变化。结果:与对照组比较,雷公藤内酯酮组小鼠肿瘤体积增长较慢,抑瘤率为43.5%;雷公藤内酯酮组小鼠肿瘤组织坏死较多;血清炎症介质肿瘤坏死因子-α(TNF-α)、白细胞介素1β(IL-1β)和C-反应蛋白(CRP)含量均明显降低(P<0.05);肿瘤组织p-IκB、p-IKK和p-NF-κB的表达量显著降低(P<0.05,);肠道菌群Alpha多样性指数显著升高(P<0.01),Beta多样性显示2组小鼠的菌群结构组成差异较大;在门水平上,p__Tenericutes丰度明显升高(P<0.05);p__Bacteroidetes、p__Firmicutes的丰度增加,p__Proteobacteria丰度减少。在属水平,雷公藤内酯酮上调有益菌g__Lachnospiraceae_NK4A136_group、g__Alloprevotella、g__Ruminiclostridium_9等丰度,下调条件致病菌g__Alistipes、 g__Enterorhabdus和Ruminiclostridium_6丰度。结论:雷公藤内酯酮具有一定的抗急性单核细胞白血病作用,其作用机制可能与抗炎、改善肠道菌群结构有关。
Objective:To observe the anti-tumor effects of triptonide on acute monocytic leukemia(AML) in mice and explore its mechanism based on anti-inflammatory activity and modulation of gut microbiota.Methods:Twenty female BALB/c nude mice were subcutaneously injected with AML cell line(U937) to establish a leukemia model.Mice were randomly divided into two groups based on tumor volume,with 8 mice per group.The triptonide group was administered by gavage at a dose of 10 mg/kg,while the control group received an equal volume of physiological saline once daily.After 2 weeks of treatment,mice were euthanized,and samples were collected.Hematoxylin-eosin(HE) staining was used to observe tumor necrosis;immunohistochemistry(IHC) was used to detect protein expression of p-IκB,p-IKK,and p-NF-κB in tumor tissues;enzyme-linked immunosorbent assay(ELISA) was used to measure serum inflammatory mediator levels;16S rRNA sequencing was used to analyze changes in gut microbiota.Results:Compared with the control group,the triptonide group showed slower tumor growth with a tumor inhibition rate of 43.5%.Tumor tissues in the triptonide group exhibited more necrosis.Serum levels of inflammatory mediators TNF-α,IL-1β,and CRP were significantly reduced(P<0.05).Expression levels of p-IκB,p-IKK,and p-NF-κB in tumor tissues were significantly decreased(P<0.05).Gut microbiota alpha diversity index significantly increased(P<0.01),and beta diversity showed substantial differences in microbiota composition between the two groups.At the phylum level,the abundance of p__Tenericutes was significantly increased(P<0.05),while p__Bacteroidetes and p__Firmicutes abundance increased,and p__Proteobacteria abundance decreased.At the genus level,triptonide upregulated beneficial bacteria such as g__Lachnospiraceae_NK4A136_group,g__Alloprevotella,and g__Ruminiclostridium_9,and downregulated pathogenic bacteria such as g__Alistipes,g__Enterorhabdus,and Ruminiclostridium_6.Conclusion:Triptonide exhibits anti-AML effects,and its mechanism may be related to i
作者
付宛鑫
宋丽霞
洪坤
程金来
周子玉
朱亚英
谭余庆
刘丽
赵保胜
FU Wanxin;SONG Lixia;HONG Kun;CHENG Jinlai;ZHOU Ziyu;ZHU Yaying;TAN Yuqing;LIU Li;ZHAO Baosheng(College of Life Sciences,Beijing University of Chinese Medicine,Beijing 102488,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Beijing Research Institute of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《世界中医药》
CAS
北大核心
2024年第13期1946-1953,共8页
World Chinese Medicine
基金
中央级公益性科研院所基本科研业务费专项(ZZ13-YQ-054,ZXKT22041)。
