Chondroitin sulfate supplementation improves clinical outcomes in a murine model of necrotizing enterocolitis.
Chondroitin sulfate supplementation improves clinical outcomes in a murine model of necrotizing enterocolitis.
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DOI：
10.14814/phy2.15819
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发表时间：
2023-09
影响因子：
2.5
通讯作者：
中科院分区：
文献类型：
--
作者：
坏死性小肠结肠炎（NEC）仍然是早产儿的一种毁灭性疾病，缺乏医疗管理选择。硫酸软骨素（CS）是人类母乳（HM）中天然存在的糖胺聚糖（GAG），已被证明可以减少炎症。我们假设在实验性NEC模型中补充CS会改变微生物多样性，有利于改变细胞因子谱，并且（像其他含硫化合物一样）通过eNOS途径改善实验性NEC的结果。在5天大的幼犬中诱导NEC。共研究6组（n = 9-15 /组）：(1)母乳喂养WT和(2)配方奶喂养对照组，(3)WT NEC, (4) WT NEC + CS, (5) eNOS KO（基因敲除）NEC, (6) eNOS KO NEC + CS。监测幼崽的临床疾病评分和体重。在出生后的第9天，幼崽被杀死。收集直肠粪便，用16s rRNA测序进行微生物组分析。使用完善的损伤评分系统对肠段进行组织学检查，并对肠段进行均质化和细胞因子分析。采用GraphPad Prism进行数据分析，p < 0.05为差异有统计学意义。与单独使用NEC相比，在配方中添加CS可改善实验NEC结果。在WT和eNOS KO小鼠中，CS补充对NEC的改善效果相似。与单独使用NEC相比，添加CS不会导致微生物变化。我们的数据表明，尽管补充CS改善了NEC的预后，但这种保护不是通过eNOS途径或微生物多样性的改变来实现的。CS治疗NEC确实改善了肠道细胞因子谱，进一步的实验将探索CS在改变这种疾病免疫途径中的机制作用。
Necrotizing enterocolitis (NEC) continues to be a devastating disease in preterm neonates and has a paucity of medical management options. Chondroitin sulfate (CS) is a naturally occurring glycosaminoglycan (GAG) in human breast milk (HM) and has been shown to reduce inflammation. We hypothesized that supplementation with CS in an experimental NEC model would alter microbial diversity, favorably alter the cytokine profile, and (like other sulfur compounds) improve outcomes in experimental NEC via the eNOS pathway. NEC was induced in 5‐day‐old pups. Six groups were studied (n = 9–15/group): (1) WT breastfed and (2) Formula fed controls, (3) WT NEC, (4) WT NEC + CS, (5) eNOS KO (knockout) NEC, and (6) eNOS KO NEC + CS. Pups were monitored for clinical sickness score and weights. On postnatal day 9, the pups were killed. Stool was collected from rectum and microbiome analysis was done with 16 s rRNA sequencing. Intestinal segments were examined histologically using a well‐established injury scoring system and segments were homogenized and analyzed for cytokine profile. Data were analyzed using GraphPad Prism with p < 0.05 considered significant. CS supplementation in formula improved experimental NEC outcomes when compared to NEC alone. CS supplementation resulted in similar improvement in NEC in both the WT and eNOS KO mice. CS supplementation did not result in microbial changes when compared to NEC alone. Our data suggest that although CS supplementation improved outcomes in NEC, this protection is not conferred via the eNOS pathway or alteration of microbial diversity. CS therapy in NEC does improve the intestinal cytokine profile and further experiments will explore the mechanistic role of CS in altering immune pathways in this disease.
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影响因子：
3.6
作者：
Knowles TA;Hosfield BD;Pecoraro AR;Li H;Shelley WC;Markel TA
通讯作者：
Markel TA
DOI：
10.15585/mmwr.mm6648a1
发表时间：
2017-12-08
期刊：
MMWR. Morbidity and mortality weekly report
影响因子：
--
作者：
Boundy EO;Perrine CG;Nelson JM;Hamner HC
通讯作者：
Hamner HC
影响因子：
2.5
作者：
Coppa, Giovanni V.;Gabrielli, Orazio;Volpi, Nicola
通讯作者：
Volpi, Nicola
DOI：
10.1152/ajpgi.00444.2016
发表时间：
2017-05-01
影响因子：
4.5
作者：
Jensen, Amanda R.;Drucker, Natalie A.;Markel, Troy A.
通讯作者：
Markel, Troy A.
影响因子：
2.4
作者：
Drucker, Natalie A.;Jensen, Amanda R.;Markel, Troy A.
通讯作者：
Markel, Troy A.