芍药甘草汤对急性肺损伤大鼠肠道菌群的影响
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篇名: 芍药甘草汤对急性肺损伤大鼠肠道菌群的影响
TITLE: Effects of Shaoyao gancao decoction on intestinal flora in rats with acute lung injury
摘要: 目的 研究芍药甘草汤(SGD)对急性肺损伤(ALI)大鼠的改善作用及对肠道菌群的影响。方法将60只大鼠按随机数字表法分为正常组(CON组,生理盐水)、模型组(MOD组,生理盐水)、阳性对照组(DEX组,5mg/kg地塞米松)和芍药甘草汤低、中、高剂量组(SGD-L、SGD-M、SGD-H组,给药剂量以生药量计分别为5.8、11.6、23.2g/kg),每组10只。各组大鼠每天灌胃1次,灌胃体积均为10mL/kg,连续7d。末次灌胃30min后,CON组大鼠气道滴注等体积生理盐水,其余各组大鼠气道滴注脂多糖(5mg/kg)建立ALI模型。造模12h后,计算大鼠肺组织湿/干重比,检测大鼠肺泡灌洗液(BALF)中白细胞介素1β(IL-1β)、IL-6和肿瘤坏死因子α(TNF-α)含量,以苏木素-伊红染色后观察肺组织病理形态学变化。采用16SrRNA测序技术分析大鼠粪便中菌群,并分析差异菌属与炎症因子的相关性。结果与MOD组比较,SGD各剂量组大鼠肺组织炎症细胞浸润均减少,肺泡隔增厚和肺泡水肿情况均有所改善;肺组织湿/干重比及BALF中IL-1β、IL-6、TNF-α水平均显著降低(P<0.05或P<0.01)。SGD(中剂量)可以改善ALI大鼠肠道菌群紊乱,恢复肠道菌群的多样性与丰富度,调节菌群结构,降低乳杆菌属、链球菌属和大肠埃氏菌属-志贺氏菌属的相对丰度,并增加厚壁菌属、毛螺菌属、瘤胃球菌属、梭状芽孢杆菌属、杜氏杆菌属和阿克曼菌属的相对丰度。相关性分析发现,乳杆菌属、链球菌属、大肠埃氏菌属-志贺氏菌属的相对丰度与炎症因子IL-1β、IL-6和TNF-α的水平呈显著正相关(P<0.05或P<0.01);毛螺菌属、杜氏杆菌属、厚壁菌属的相对丰度与上述炎症因子的水平呈显著负相关(P<0.05或P<0.01)。结论SGD可能通过减轻大鼠肺组织损伤和炎症反应、调节菌群结构来改善ALI。
ABSTRACT: OBJECTIVE To study the improvement effects of Shaoyao gancao decoction (SGD) on acute lung injury (ALI) in rats and its effects on the intestinal flora. METHODS Sixty SD rats were randomly divided into normal group (CON group, normal saline), model group (MOD group, normal saline), positive control group (DEX group, 5 mg/kg dexamethasone), SGD low-dose, medium-dose and high-dose groups (SGD-L, SGD-M, SGD-H groups, 5.8, 11.6, 23.2 g/kg, calculated by crude drug), with 10 rats in each group. Each group was given relevant medicine 10 mL/kg intragastrically, for 7 consecutive days. Thirty minutes after the last administration, CON group was given constant volume of normal saline via airway infusion, and other groups were given lipopolysaccharide (5 mg/kg) via airway infusion to induce ALI model. After 12 hours of modeling, the lung tissue wet/dry weight ratio was calculated, and the contents of interleukin 1β (IL-1β), IL-6 and tumor necrosis factor α(TNF-α) in rat bronchial alveolar lavage fluid (BALF) were all detected; the pathological changes of lung tissue were observed after hematoxylin-eosin staining. The intestinal flora of rat feces was analyzed by 16S rRNA sequencing technology, and the correlation of differential bacteria genera with inflammatory factors was also analyzed. RESULTS Compared with MOD group, the infiltration of inflammatory cells in the lung tissue of rats in each SGD dose group was decreased, and the thickening of alveolar septum and pulmonary edema improved; lung tissue wet/dry weight ratio, the levels of IL-1β, IL-6 and TNF-α in BALF significantly decreased (P<0.05 or P<0.01). SGD (low dose) could improve the intestinal flora disorder in ALI rats, restore the diversity and richness of intestinal flora, regulate the structure of flora, reduce the abundance of Lactobacillus, Streptococcus and Escherichia-Shigella, and increase the abundance of Firmicutes, Lachnospira, Ruminococcus, Clostridia,Dubosiella and Akkermansia. Through correlation analysis, it was found that the relative abundance of Lactobacillus, Streptococcus and Escherichia-Shigella was positively related to the levels of inflammatory factor IL-1β, IL-6 and TNF-α (P<0.05 or P<0.01). The relative abundance of Lachnospira, Dubosiella, Firmicutes was significantly negatively correlated with the levels of inflammatory factors mentioned above (P<0.05 or P<0.01). CONCLUSIONS SGD may improve ALI by reducing lung tissue injury and inflammatory response and regulating flora structure in rats.
期刊: 2023年第34卷第17期
作者: 张甘纯;刘文;宋信莉;刘兴德;舒万芬;秦琴;王洪鑫
AUTHORS: ZHANG Ganchun,LIU Wen,SONG Xinli,LIU Xingde,SHU Wanfen,QIN Qin,WANG Hongxin
关键字: 芍药甘草汤;急性肺损伤;肠道菌群;16S rRNA测序;炎症反应
KEYWORDS: Shaoyao gancao decoction; acute lung injury; intestinal flora; 16S rRNA sequencing; inflammatory response
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