Effects of <italic style="font-style: italic">Xiaochengqi Decoction </italic>（小承气汤） on Intestinal Flora in Rats with Acute Severe Traumatic Brain Injury

Lingling PENG; Renjiu LIANG; Ling NING; Yiheng DU; Guihua HUANG

doi:10.13288/j.11-2166/r.2022.12.013

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Effects of Xiaochengqi Decoction （小承气汤） on Intestinal Flora in Rats with Acute Severe Traumatic Brain Injury

更新时间：2022-06-10

- Effects of Xiaochengqi Decoction （小承气汤） on Intestinal Flora in Rats with Acute Severe Traumatic Brain Injury
- Journal of Traditional Chinese Medicine Vol. 63, Issue 12, Pages: 1170-1178(2022)
- 作者机构：
  
  1.广西中医药大学，广西壮族自治区南宁市青秀区五合大道13号，530200
  2.广西医科大学第一附属医院
  3.湖南中医药大学
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2022.12.013
  CLC：
- Received：26 November 2021，
  
  Revised：2022-02-28，
  
  Published：17 June 2022
- 稿件说明：
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彭玲玲,梁仁久,宁玲等.小承气汤对重型颅脑损伤模型大鼠急性期肠道菌群的影响[J].中医杂志,2022,63(12):1170-1178.

PENG Lingling,LIANG Renjiu,NING Ling,et al.Effects of Xiaochengqi Decoction （小承气汤） on Intestinal Flora in Rats with Acute Severe Traumatic Brain Injury[J].Journal of Traditional Chinese Medicine,2022,63(12):1170-1178.
彭玲玲,梁仁久,宁玲等.小承气汤对重型颅脑损伤模型大鼠急性期肠道菌群的影响[J].中医杂志,2022,63(12):1170-1178. DOI： 10.13288/j.11-2166/r.2022.12.013.

PENG Lingling,LIANG Renjiu,NING Ling,et al.Effects of Xiaochengqi Decoction （小承气汤） on Intestinal Flora in Rats with Acute Severe Traumatic Brain Injury[J].Journal of Traditional Chinese Medicine,2022,63(12):1170-1178. DOI： 10.13288/j.11-2166/r.2022.12.013.

摘要

目的

从肠道菌群角度探讨小承气汤治疗重型颅脑损伤（sTBI）的可能作用机制。

方法

将 90只SD大鼠随机分为正常组、假手术组、模型组、金双歧组、小承气汤组，每组18只。模型组、金双歧组、小承气汤组大鼠采用Freeney's自由落体法制作sTBI大鼠模型，造模成功6 h后，金双歧组、小承气汤组分别给予金双歧6.17 g/kg和小承气汤2.78 g/kg灌胃干预，正常组、假手术组、模型组给予2.78 ml/（kg·d）生理盐水灌胃。干预7 d后观察大鼠神经功能缺损（NSS）评分，HE染色观察脑、结肠组织病理改变，16S rRNA测序技术分析大鼠结肠菌群的变化，蛋白质免疫印迹法检测大鼠脑、结肠组织白细胞介素1β（IL-1β）表达，酶联免疫吸附试验检测血清IL-1β含量。

结果

假手术组与正常组各指标差异均无统计学意义（

＞0.05）。与正常组比较，模型组大鼠体重下降、NSS评分升高（

＜0.01）。HE染色显示，模型组大鼠神经细胞排列紊乱，大量神经元坏死，散在存活的神经细胞肿胀、间质疏松，结肠黏膜完整性破坏、肠腺排列紊乱、肠间隙增宽、黏膜水肿，脑、结肠组织和血清IL-1β水平升高（

＜0.01），模型组大鼠肠道菌群多样性香农（Shannon）和辛普森（Simpson）指数下降，厚壁菌门、螺旋体门相对丰度下降，拟杆菌门、变形菌门、迷踪菌门、放线菌门、广古菌门相对丰度升高，毛螺科、瘤胃菌科、拟杆菌科_S24-7_组、螺旋体科相对丰度明显下降，拟杆菌科、迷踪菌科、肠杆菌科、产碱杆菌科相对丰度上升，毛螺科_NK4A136_组、毛螺科_UCG-005、罗姆布茨菌属、罗氏菌属、普雷沃氏菌_NK3B31_组、普雷沃氏菌_UCG-001、异普雷沃氏菌属、螺旋体_2相对丰度明显下降，拟杆菌属、埃希志贺菌、副拟杆菌属、迷踪门菌属相对丰度上升（

＜0.05或

＜0.01）。与模型组比较，小承气汤组和金双歧组大鼠体重升高、NSS评分下降（

＜0.05或

＜0.01），脑和结肠组织病理改变减轻，脑、结肠组织和血清IL-1β水平均显著下降（

＜0.01），小承气汤组较金双歧组血清IL-1β下降程度更显著（

＜0.05）。与模型组比较，小承气汤组肠道菌群Shannon、Observed_species指数上升（

＜0.01），除了广古菌门、拟杆菌科_S24-7_组、普雷沃氏_UCG-001无明显变化之外，小承气汤逆转了模型组中发生改变菌群的相对丰度变化趋势（

＜0.05）。

结论

小承气汤可以改善sTBI模型大鼠肠道菌群失调，促进产短链脂肪酸等有益菌生长，抑制产内毒素有害菌，减轻继发炎症反应，这可能是其治疗sTBI的作用机制之一。

Abstract

Objective

To explore the possible mechanism of

Xiaochengqi Decoction

（小承气汤， XCQD） in the treatment of rats with acute severe traumatic brain injury （sTBI） from the perspective of intestinal flora.

Methods

A total of 90 SD rats were randomly divided into normal group， sham operation group， model group， golden bifid group and XCQD group， with 18 rats in each group. The sTBI rat model was made using Freeney

s free fall method in the model group， golden bifid group and XCQD group. Six hours after successful modeling， 6.17 g/kg of golden bifid and 2.78 g/kg of XCQD was given into the corresponding group by gavage， respectively， while 2.78 ml/（kg·d） of normal saline were administered by gavage in the normal group， sham operation group and model group. After seven days of intervention， the neurological severity score （NSS） was assessed. Pathological changes of brain tissue and colon were observed through hematoxylin eosin （HE） staining， and changes of colon flora were analyzed by 16S rRNA sequencing. The expression of interleukin-1beta （IL-1β） in brain and colon tissue was detected by Western blotting， and serum IL-1β level was detected by enzyme-linked immunosorbent assay （ELISA）.

Results

There was no significant difference between the normal and sham operation group in all outcomes （

＞0.05）. Compared with the normal group， the model group had reduced weight and increased NSS （

＜0.01）. HE staining showed that there was brain tissue structure disorder， abundant necrotic neurons， cell swelling and interstitial edema of the scattered living nerve cells， destruction of mucosal integrity， disorder of intestinal gland arrangement， widening of intestinal space and mucosal edema in the model group. Compared with those in the normal group， the expression of IL-1β in brain and colon tissue and the serum IL-1β level in the model group significantly increased （

＜0.01）. The Shannon and Simpson diversity indexes in the model group decreased； the relative abundance of Firmicutes and Spirochetes decreased， while the abundance of Bacteroidetes， Proteobacteria， Elusimicrobia， Actinobacteria， and Euryarchaeota increased； the relative abundance of Lachnospiraceae， Ruminococcaceae， Bacteroidales_S24-7 group and Spirochaetaceae decreased significantly， while the abundance of Bacteroideae， Enterobacteriaceae， Elusimicrobiaceae and Alcaligenaceae increased； the relative abundance of Lachnospiraceae_NK4A136_group， Lachnospiraceae_UCG-005， Romboutsia， Poseburia， Prevotellaceae_NK3B31_group， Prevotellaceae_UCG-001， Alloprevotella and Treponema_2 decreased， and the abundance of Bacteroides， Escherichia-Shigella， Parabacteroides and Elusimicrobium increased （

＜0.05 or

＜0.01）. Compared with the model group， the XCQD and the golden bifid group had higher weight of the rats and lower NSS （

＜0.05 or

＜0.01）， as well as decreased pathological changes in the brain and colon tissue， the expression of IL-1β in brain and colon tissue， and the serum IL-1β level （

＜0.01）， with more decreases of serum IL-1β level in the XCQD group （

＜0.05）. Compared with the model group， the Shannon and Observed_species indexes of the intestinal flora in the XCQD group increased （

＜0.01）. The abondance of those changed in model group were reversed in the opposite direction except Euryarchaeota， Bacteroidales_S24-7 group and Prevotella-UCG-001 （

＜0.05）.

Conclusion

XCQD can improve intestinal flora imbalance， promote the growth of beneficial bacteria producing short chain fatty acids， inhibit harmful bacteria producing endotoxin， and reduce the secondary inflammatory response， which may explain its mechanism in treatment of sTBI model rats.

关键词

Keywords

references

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Effects of Xiaochengqi Decoction （小承气汤） on Intestinal Flora in Rats with Acute Severe Traumatic Brain Injury

DOI：10.13288/j.11-2166/r.2022.12.013

摘要

Abstract

关键词

Keywords

references