Effects of Shaoyao gancao decoction on intestinal flora in rats with acute lung injury

ZHANG Ganchun; LIU Wen; SONG Xinli; LIU Xingde; SHU Wanfen; QIN Qin; WANG Hongxin

doi:10.6039/j.issn.1001-0408.2023.17.03

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Effects of Shaoyao gancao decoction on intestinal flora in rats with acute lung injury

更新时间：2023-09-14

- Effects of Shaoyao gancao decoction on intestinal flora in rats with acute lung injury
- ZHONGGUO YAOFANG Vol. 34, Issue 17, Pages: 2063-2068(2023)
- 作者机构：
  
  1.贵州中医药大学药学院，贵阳　550025
  2.贵州医科大学药学院，贵阳　550025
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.17.03
  CLC： R965;R285
- Published：15 September 2023，
  
  Received：12 March 2023，
  
  Revised：06 August 2023，
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张甘纯,刘文,宋信莉等.芍药甘草汤对急性肺损伤大鼠肠道菌群的影响 ^Δ[J].中国药房,2023,34(17):2063-2068.

ZHANG Ganchun,LIU Wen,SONG Xinli,et al.Effects of Shaoyao gancao decoction on intestinal flora in rats with acute lung injury[J].ZHONGGUO YAOFANG,2023,34(17):2063-2068.
张甘纯,刘文,宋信莉等.芍药甘草汤对急性肺损伤大鼠肠道菌群的影响 ^Δ[J].中国药房,2023,34(17):2063-2068. DOI： 10.6039/j.issn.1001-0408.2023.17.03.

ZHANG Ganchun,LIU Wen,SONG Xinli,et al.Effects of Shaoyao gancao decoction on intestinal flora in rats with acute lung injury[J].ZHONGGUO YAOFANG,2023,34(17):2063-2068. DOI： 10.6039/j.issn.1001-0408.2023.17.03.

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，5 mg/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、23.2 g/kg），每组10只。各组大鼠每天灌胃1次，灌胃体积均为10 mL/kg，连续7 d。末次灌胃30 min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（5 mg/kg）建立ALI模型。造模12 h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16S rRNA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（

＜0.05或

＜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（

＜0.05或

＜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（

＜0.05或

＜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 （

＜0.05 or

＜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 （

＜0.05 or

＜0.01）. The relative abundance of

Lachnospira

，

Dubosiella

，

Firmicutes

was significantly negatively correlated with the levels of inflammatory factors mentioned above （

＜0.05 or

＜0.01）.

CONCLUSIONS

SGD may improve ALI by reducing lung tissue injury and inflammatory response and regulating flora structure in rats.

关键词

芍药甘草汤急性肺损伤肠道菌群16S rRNA测序炎症反应

Keywords

acute lung injuryintestinal flora16S rRNA sequencinginflammatory response

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