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大肠杆菌 H10407 诱导腹泻的分子机制及其通过丝柏(Simarouba amara(Aubl.))生物活性物质的免疫调节作用进行控制。

Molecular mechanism of Escherichia coli H10407 induced diarrhoea and its control through immunomodulatory action of bioactives from Simarouba amara (Aubl.).

机构信息

Department of Microbiology, Kuvempu University, Jnana Sahyadri, Shankaraghatta, Shivamogga, 577451, Karnataka, India.

Niranthara Scientific Solutions Pvt. Ltd, Bengaluru, 560060, Karnataka, India.

出版信息

J Microbiol. 2021 Apr;59(4):435-447. doi: 10.1007/s12275-021-0423-2. Epub 2021 Feb 25.

DOI:10.1007/s12275-021-0423-2
PMID:33630248
Abstract

Enterotoxigenic Escherichia coli (ETEC) infection is a major cause of death in children under the age of five in developing countries. ETEC (O78:H11:CFA/I:LT:ST) mechanism has been studied in detail with either heat labile (LT) or heat stable (ST) toxins using in vitro and in vivo models. However, there is no adequate information on ETEC pathogenesis producing both the toxins (LT, ST) in BALB/c mice model. In this study, female mice have been employed to understand ETEC H10407 infection induced changes in physiology, biochemical and immunological patterns up to seven days post-infection and the antidiarrhoeal effect of Simarouba amara (Aubl.) bark aqueous extract (SAAE) has also been looked into. The results indicate that BALB/c is sensitive to ETEC infection resulting in altered jejunum and ileum histomorphology. Withal, ETEC influenced cAMP, PGE2, and NO production resulting in fluid accumulation with varied Na, K, Cl, and Ca levels. Meanwhile, ETEC subverted expression of IL-1β, intestine alkaline phosphatase (IAP), and myeloperoxidase (MPO) in jejunum and ileum. Our data also indicate the severity of pathogenesis reduction which might be due to attainment of equilibrium after reaching optimum rate of infection. Nevertheless, degree of pathogenesis was highly significant (p < 0.01) in all the studied parameters. Besides that, SAAE was successful in reducing the infectious diarrhoea by inhibiting ETEC H10407 in intestine (jejunum and ileum), and shedding in feces. SAAE decreased cAMP, PGE2, and fluid accumulation effectively and boosted the functional activity of immune system in jejunum and ileum IAP, MPO, IL-1β, and nitric oxide.

摘要

产肠毒素性大肠杆菌(ETEC)感染是发展中国家 5 岁以下儿童死亡的主要原因。已经使用体外和体内模型详细研究了 ETEC(O78:H11:CFA / I:LT:ST)机制,无论是使用不耐热(LT)还是耐热(ST)毒素。然而,在 BALB/c 小鼠模型中产生两种毒素(LT,ST)的 ETEC 发病机制没有足够的信息。在这项研究中,使用雌性小鼠来了解 ETEC H10407 感染诱导的生理,生化和免疫模式的变化,直至感染后 7 天,并研究了苦配巴(Simarouba amara(Aubl.)树皮水提取物(SAAE)的抗腹泻作用。结果表明,BALB / c 对 ETEC 感染敏感,导致空肠和回肠组织形态发生改变。尽管如此,ETEC 影响 cAMP,PGE2 和 NO 的产生,导致液体积累并伴有不同的 Na,K,Cl 和 Ca 水平。同时,ETEC 颠覆了空肠和回肠中 IL-1β,肠碱性磷酸酶(IAP)和髓过氧化物酶(MPO)的表达。我们的数据还表明,发病机制的严重程度降低可能是由于达到最佳感染率后达到平衡。尽管如此,所有研究参数的发病机制程度均具有高度显著性(p <0.01)。此外,SAAE 通过抑制肠(空肠和回肠)中的 ETEC H10407 和粪便中的脱落,成功地减少了传染性腹泻。 SAAE 有效地减少了 cAMP,PGE2 和液体积累,并增强了空肠和回肠中 IAP,MPO,IL-1β和一氧化氮的免疫系统功能活性。

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