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维生素D通过调节肠道微生物群改善大鼠脂多糖诱导的重症肺炎。

Vitamin D Improves -Induced Severe Pneumonia in Rats by Regulating Intestinal Microbiota.

作者信息

Hu Jia-Jia, Lin Yu-Sen, Zhang Jing-Cong, Wang Yan-Hong

机构信息

Medical Intensive Care Unit, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.

出版信息

Infect Drug Resist. 2024 Feb 8;17:475-484. doi: 10.2147/IDR.S442330. eCollection 2024.

Abstract

BACKGROUND

In the context of progressively uncontrolled drug resistance of bacteria, the difficulty of treating (KP)-induced pneumonia increases. Searching for drugs other than antibiotics has become an urgent task. Vitamin D (VD), meanwhile, is shown to be capable of treating pneumonia. Therefore, we aimed to explore the effects and mechanisms of VD on KP-infected rats.

METHODS

Male Sprague Dawley rats were divided into the Control, VD, KP and KP+VD groups. A rat pneumonia model was induced using an intratracheal drop of 2.4×10 CFU/mL KP. VD treatment was performed by gavage using 5 μg/kg. Subsequently, the survival of the rats was recorded, and the lungs, bronchoalveolar lavage fluid, and feces of the rats were collected 4 days after KP infection. Next, the water content of lung tissues was measured by the wet-to-dry weight ratio. Histopathological changes of lung tissues were observed by Hematoxylin and Eosin staining and the levels of inflammatory factors (TNF-α, IL-1β, MCP1) were detected using ELISA. The feces of rats in each group were also subjected to 16S rDNA gene analysis of intestinal microbiota.

RESULTS

Compared with the KP group, the KP+VD group showed a significant increase in survival, a significant decrease in water content and bacterial counts in the lungs, a significant improvement in lung injury, and a significant decline in the levels of TNF-α, IL-1β, and MCP1. According to the 16S rDNA sequencing, VD altered the structure of the intestinal bacterial community in the KP-infected rats and made the species richness similar to that of healthy rats. Additionally, the abundance of was significantly increased in the KP+VD group.

CONCLUSION

VD modulates intestinal microbiota to increase the resistance of rats to pneumonia caused by infection.

摘要

背景

在细菌耐药性逐渐失控的背景下,治疗肺炎克雷伯菌(KP)所致肺炎的难度增加。寻找抗生素以外的药物已成为一项紧迫任务。与此同时,维生素D(VD)已被证明能够治疗肺炎。因此,我们旨在探讨VD对感染KP的大鼠的影响及其机制。

方法

将雄性Sprague Dawley大鼠分为对照组、VD组、KP组和KP + VD组。通过气管内滴注2.4×10 CFU/mL的KP建立大鼠肺炎模型。采用5 μg/kg的剂量通过灌胃进行VD治疗。随后,记录大鼠的存活情况,并在KP感染后4天收集大鼠的肺、支气管肺泡灌洗液和粪便。接下来,通过湿重与干重之比测量肺组织的含水量。采用苏木精和伊红染色观察肺组织的组织病理学变化,并使用酶联免疫吸附测定法检测炎症因子(TNF-α、IL-1β、MCP1)的水平。还对每组大鼠的粪便进行肠道微生物群的16S rDNA基因分析。

结果

与KP组相比,KP + VD组的存活率显著提高,肺组织的含水量和细菌计数显著降低,肺损伤显著改善,TNF-α、IL-1β和MCP1的水平显著下降。根据16S rDNA测序结果,VD改变了感染KP的大鼠肠道细菌群落的结构,使其物种丰富度与健康大鼠相似。此外,KP + VD组中 的丰度显著增加。

结论

VD调节肠道微生物群,以提高大鼠对KP感染所致肺炎的抵抗力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b2/10860834/c3cfc9270d0f/IDR-17-475-g0001.jpg

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