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通过维持肠道屏障功能和调节肠道微生物群对大鼠中暑的预防作用

Preventive Effects of on Heat Stroke in Rats by Sustaining Intestinal Barrier Function and Modulating Gut Microbiota.

作者信息

Li Lei, Wang Man, Chen Jikuai, Xu Zhuoran, Wang Shaokang, Xia Xinyu, Liu Dong, Wang Sheng, Xie Chaoyu, Wu Jianghong, Li Jinfeng, Zhang Jiqianzhu, Wang Meitang, Zhu Jiangbo, Ling Changquan, Xu Shuogui

机构信息

Department of Emergency, Changhai Hospital, Naval Medical University, Shanghai, China.

School of Traditional Chinese Medicine, Naval Medical University, Shanghai, China.

出版信息

Front Microbiol. 2021 Apr 6;12:630841. doi: 10.3389/fmicb.2021.630841. eCollection 2021.

Abstract

Heat stroke (HS) models in rats are associated with severe intestinal injury, which is often considered as the key event at the onset of HS. Probiotics can regulate the gut microbiota by inhibiting the colonization of harmful bacteria and promoting the proliferation of beneficial bacteria. Here, we investigated the preventive effects of a probiotic strain (BL, CMCC 63516) on HS rats as well as its effects on intestinal barrier function and gut microbiota. All rats were randomly divided into four groups: control (Con) + PBS (pre-administration with 1 ml PBS twice a day for 7 days, without HS induction), Con + BL group (pre-administration with 1 ml 1 × 10 CFU/ml BL twice a day for 7 days, without HS induction), HS + PBS (PBS, with HS induction), and HS + BL (BL, with HS induction). Before the study, the BL strain was identified by genomic DNA analysis. Experimental HS was induced by placing rats in a hot and humid chamber for 60 min until meeting the diagnostic criterion of HS onset. Body weight, core body temperature, survival rate, biochemical markers, inflammatory cytokines, and histopathology were investigated to evaluate the preventive effects of BL on HS. D-Lactate, I-FABP, endotoxin, and tight-junction proteins were investigated, and the fluorescein isothiocyanate-dextran (FD-4) test administered, to assess the degree of intestinal injury and integrity. Gut microbiota of rats in each group were analyzed by 16S rRNA sequencing. The results showed that pre-administration with BL significantly attenuated hyperthermia, reduced HS-induced death, alleviated multiple-organ injury, and decreased the levels of serum inflammatory cytokines. Furthermore, BL sustained the intestinal barrier integrity of HS rats by alleviating intestinal injury and improving tight junctions. We also found that BL significantly increased the ratios of two probiotic bacteria, and . In addition, , a candidate biomarker for HS diagnosis, was unexpectedly detected. In summary, BL pre-administration for 7 days has preventative effects on HS that may be mediated by sustaining intestinal barrier function and modulating gut microbiota.

摘要

大鼠中暑(HS)模型与严重的肠道损伤有关,肠道损伤常被认为是中暑发病的关键事件。益生菌可通过抑制有害细菌的定植和促进有益细菌的增殖来调节肠道微生物群。在此,我们研究了一种益生菌菌株(BL,中国医学微生物菌种保藏管理中心63516)对中暑大鼠的预防作用及其对肠道屏障功能和肠道微生物群的影响。所有大鼠随机分为四组:对照组(Con)+ PBS(每天两次腹腔注射1 ml PBS,共7天,未诱导中暑),Con + BL组(每天两次腹腔注射1 ml 1×10 CFU/ml BL,共7天,未诱导中暑),HS + PBS组(PBS,诱导中暑),以及HS + BL组(BL,诱导中暑)。在研究开始前,通过基因组DNA分析对BL菌株进行鉴定。通过将大鼠置于湿热箱中60分钟直至达到中暑发病的诊断标准来诱导实验性中暑。研究体重、核心体温、存活率、生化标志物、炎性细胞因子和组织病理学,以评估BL对中暑的预防作用。检测D-乳酸、肠脂肪酸结合蛋白(I-FABP)、内毒素和紧密连接蛋白,并进行异硫氰酸荧光素-葡聚糖(FD-4)试验,以评估肠道损伤程度和完整性。通过16S rRNA测序分析每组大鼠的肠道微生物群。结果表明,预先给予BL可显著减轻体温过高,降低中暑诱导的死亡,减轻多器官损伤,并降低血清炎性细胞因子水平。此外,BL通过减轻肠道损伤和改善紧密连接来维持中暑大鼠的肠道屏障完整性。我们还发现,BL显著增加了两种益生菌和的比例。此外,意外检测到一种中暑诊断的候选生物标志物。总之,预先给予BL 7天对中暑具有预防作用,其机制可能是通过维持肠道屏障功能和调节肠道微生物群来介导的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b8f/8055866/f7e47c79391d/fmicb-12-630841-g001.jpg

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