Protective effects of parthenolide on intestinal barrier function in septic rats

Ningke GUO; Han SHE; Lei TAN; Yuanqun ZHOU; Xiaoyong PENG; Tao LI; Liangming LIU

doi:10.16016/j.2097-0927.202205042

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Protective effects of parthenolide on intestinal barrier function in septic rats

Monographic Reports: Treatment of war wound and traumatic shock | 更新时间：2026-01-09

- Protective effects of parthenolide on intestinal barrier function in septic rats
- Journal of Army Medical University Vol. 44, Issue 20, Pages: 2068-2074(2022)
- 作者机构：
  
  1.453000 河南新乡，新乡医学院第三附属医院外科
  2.400042 重庆，陆军特色医学中心战伤休克与输血研究室，创伤、烧伤与复合伤国家重点实验室
- 作者简介：
- 基金信息：
  
  the Key Program of National Natural Science Foundation of China(81830065)
- DOI：10.16016/j.2097-0927.202205042
  CLC： R285.5;R322.45;R631.2
- Received：10 May 2022，
  
  Revised：2022-07-14，
  
  Published：30 October 2022
- 稿件说明：
移动端阅览
Ningke GUO, Han SHE, Lei TAN, et al. Protective effects of parthenolide on intestinal barrier function in septic rats[J]. Journal of Army Medical University, 2022, 44(20): 2068-2074.
DOI：

Ningke GUO, Han SHE, Lei TAN, et al. Protective effects of parthenolide on intestinal barrier function in septic rats[J]. Journal of Army Medical University, 2022, 44(20): 2068-2074. DOI： 10.16016/j.2097-0927.202205042.

摘要

目的

探讨小白菊内酯(parthenolide，PTL)对脓毒症大鼠肠屏障功能的保护作用。

方法

采用盲肠结扎穿孔(cecal ligation and puncture，CLP)制作脓毒症大鼠模型，将SD大鼠(雌雄不拘，200±20 g)随机分为6组：正常对照(Normal)组、脓毒症(Sep)组、常规治疗(LR)组(乳酸林格氏液复苏+多巴胺+头孢呋辛钠)和小白菊内酯1、5、10 mg/kg治疗(PTL)组(常规治疗基础上分别给予3种浓度小白菊内酯)。观察各组大鼠动脉血压的变化、存活率和存活时间的变化，确定小白菊内酯治疗脓毒症大鼠的最佳浓度；观察最佳浓度小白菊内酯对脓毒症大鼠肠通透性和肠道病理、血炎症细胞因子水平及肝肾功能的影响。

结果

与正常对照组比较，脓毒症组大鼠存活率与存活时间显著降低，平均动脉压(mean arterial blood pressure，MAP)明显下降，血炎症细胞因子水平升高，肝肾功能损伤；常规治疗可一定程度改善脓毒症大鼠存活率和存活时间，降低血炎症细胞因子水平，改善肝肾功能。1、5、10 mg/kg小白菊内酯组大鼠存活率较常规治疗组分别升高6.3%、43.8%、18.8%，平均动脉血压分别上升1.4%、12.8%、7.1%；其中5 mg/kg组效果最好。小白菊内酯可显著改善脓毒症大鼠肠屏障功能，表现为肠伊文思蓝(Evans blue，EB)含量较常规治疗降低55.1%，血D-乳酸浓度降低69.5%，肠上皮结构改善，上皮细胞坏死减少。小白菊内酯还可显著降低血炎症细胞因子水平，改善脓毒症大鼠肝肾功能。

结论

小白菊内酯对脓毒症大鼠肠屏障功能具有明显的保护作用，其机制可能与抑制脓毒症炎症反应有关。

Abstract

Objective

To investigate the protective effects of parthenolide (PTL) on intestinal barrier function in septic rats.

Methods

The septic model of rats was established by cecal ligation and puncture (CLP)

and SD rats (200±20 g

male/female) were randomly divided into 6 groups: normal control (NC) group

sepsis (Sep) group

conventional treatment (LR) group (lactated Ringer's solution resuscitation+dopamine+cefuroxime sodium)

and parthenolide (PTL) groups (1

5 and 10 mg/kg parthenolide respectively on the basis of LR group). The changes of arterial blood pressure

survival rate and survival time of rats in each group were observed

and the optimal concentration of parthenolide in the treatment was determined. Moreover

the effects of parthenolide (at the optimal concentration) on the intestinal permeability

intestinal pathology

inflammatory cytokine levels

as well as liver and kidney functions in septic rats were further investigated.

Results

As compared with the NC group

the survival rate and survival time of septic rats were significantly decreased

so was the mean arterial pressure (MAP)

while the levels of blood inflammatory cytokines were increased

and the liver and kidney functions were damaged. Conventional treatment improved the survival rate and survival time of septic rats to a certain extent

reduced the levels of inflammation cytokines and alleviated the liver and kidney damages. When compared with the LR group

the survival rates of 1

and 10 mg/kg PTL groups were increased by 6.3%

43.8%

and 18.8%

respectively

and the MAP in the PTL groups was elevated by 1.4%

12.8%

and 7.1%

respectively

with those of 5 mg/kg PTL more significant. Further research found that PTL remarkably ameliorated the intestinal barrier function in septic rats

shown as a 55.1% reduction in the content of intestinal Evans blue (EB)

a 69.5% decline in blood D-lactic acid concentration as compared with the LR group (

0.05)

along with an improvement in intestinal epithelial structure

and a decrease in epithelial cell necrosis. In addition

PTL reduced the inflammatory cytokine levels greatly and improved the liver and kidney functions in septic rats.

Conclusion

PTL shows obvious protective effects on the intestinal barrier function of septic rats

and its mechanism may be related to the inhibition of septic inflammatory response.

关键词

Keywords

references

SHE H, ZHU Y, DENG H Y, et al . Protective effects of dexmedetomidine on the vascular endothelial barrier function by inhibiting mitochondrial fission via ER/mitochondria contact[J ] . Front Cell Dev Biol, 2021, 9: 636327. DOI: 10.3389/fcell.2021.636327.

陈作. 脓毒症诱导的肠损伤及其防治措施的研究进展[J]. 实用医技杂志, 2018, 25(12): 1372-1373. DOI: 10.19522/j.cnki.1671-5098.2018.12.024.

CHEN Z. Research progress on sepsis-induced intestinal injury and its prevention and treatment[J]. J Pract Med Tech, 2018, 25(12): 1372-1373. DOI: 10.19522/j.cnki.1671-5098.2018.12.024

ADELMAN M W, WOODWORTH M H, LANGELIER C, et al . The gut microbiome's role in the development, maintenance, and outcomes of Sepsis [J ] . Crit Care, 2020, 24(1): 278. DOI: 10.1186/s13054-020-02989-1..

曹钰, 柴艳芬, 邓颖, 等. 中国脓毒症/脓毒性休克急诊治疗指南(2018)[J]. 临床急诊杂志, 2018, 19(9): 567-588. DOI: 10.13201/j.issn.1009-5918.2018.09.001.

CAO Y, CHAI Y F, DENG Y, et al . Guidelines for emergency treatment of sepsis/septic shock in China (2018)[J ] . J Clin Emerg, 2018, 19(9): 567-588. DOI: 10.13201/j.issn.1009-5918.2018.09.001.

王哲, 王佳贺. 小白菊内酯药理作用的研究进展[J]. 中医药导报, 2019, 25(23): 112-115. DOI: 10.13862/j.cnki.cn43-1446/r.2019.23.029.

WANG Z, WANG J H. Advances in studies on pharmacological effect of parthenolide[J]. Guid J Tradit Chin Med Pharm, 2019, 25(23): 112-115. DOI: 10.13862/j.cnki.cn43-1446/r.2019.23.029.

SIVARAJASINGAM S P, IMAMI N, JOHNSON M R. Myometrial cytokines and their role in the onset of labour[J]. J Endocrinol, 2016, 231(3): R101-R119. DOI: 10.1530/JOE-16-0157.

乔会敏, 陈林玉, 杜媛媛, 等. 小白菊内酯对脑缺血大鼠的脑保护作用及机制[J]. 河北医药, 2021, 43(8): 1161-1164, 1169. DOI: 10.3969/j.issn.1002-7386.2021.08.008.

QIAO H M, CHEN L Y, DU YY, et al . Neuroprotective effects and action mechanism of parthenolide in rats with cerebral ischemia[J ] . Hebei Med J, 2021, 43(8): 1161-1164, 1169. DOI: 10.3969/j.issn.1002-7386.2021.08.008.

HUA R Y, EDEY L F, O'DEA K P, et al . CCR2 mediates the adverse effects of LPS in the pregnant mouse[J ] . Biol Reprod, 2020, 102(2): 445-455. DOI: 10.1093/biolre/ioz188.

王洪晨, 周赫男, 郑丹阳, 等. 周细胞微囊泡对脓毒症大鼠肺损伤的保护作用[J]. 第三军医大学学报, 2021, 43(13): 1185-1191. DOI: 10.16016/j.1000-5404.202101031.

WANG H C, ZHOU H N, ZHENG D Y, et al . Pericyte derived microvesicles protects septic rats against lung injury[J ] . J Third Mil Med Univ, 2021, 43(13): 1185-1191. DOI: 10.16016/j.1000-5404.202101031.

朱娱, 吴跃, 张杰, 等. 线粒体靶向抗氧化肽SS-31对脓毒症大鼠血管通透性的保护作用[J]. 第三军医大学学报, 2019, 41(3): 199-205. DOI: 10.16016/j.1000-5404.201808002.

ZHU Y, WU Y, ZHANG J, et al . Mitochondria-targeted peptide SS-31 protects septic rats against vascular permeability[J ] . J Third Mil Med Univ, 2019, 41(3): 199-205. DOI: 10.16016/j.1000-5404.201808002.

郑丹阳. 间充质干细胞微囊泡对脓毒症肠屏障及肺血管屏障功能的保护作用及机制[D]. 重庆: 陆军军医大学, 2021.

ZHENG D Y. The protective effects and mechanisms of mesenchymal stem cell-derived microvesicles on intestinal barrier and pulmonary vascular barrier function during sepsis[D]. Chongqing: Army Medical University, 2021.

王军, 张乐, 郭丽萍, 等. 小白菊内酯通过NF-κB信号通路对LPS诱导的气道上皮细胞IL-8分泌水平影响的研究[J]. 临床和实验医学杂志, 2019, 18(17): 1823-1827. DOI: 10.3969/j.issn.1671-4695.2019.17.009.

WANG J, ZHANG L, GUO L P, et al . The effect of parithenolide on the level of IL-8 in LPS-induced airway epithelium cells by via NF-κB signaling pathway[J ] . J Clin Exp Med, 2019, 18(17): 1823-1827. DOI: 10.3969/j.issn.1671-4695.2019.17.009..

HU Q Y, REN H J, LI G W, et al . STING-mediated intestinal barrier dysfunction contributes to lethal sepsis[J ] . EBioMedicine, 2019, 41: 497-508. DOI: 10.1016/j.ebiom.2019.02.055.

XU Z, LI D, QU W, et al . Card9 protects sepsis by regulating Ripk2-mediated activation of NLRP3 inf-lammasome in macrophages. Cell DeathDis, 2022, 13(5): 502. Published 2022 May26. DOI: 10.1038/s41419-022-04938-y.

KIM E, TRAN M, SUN Y Y, et al . Isolation and analyses of Lamina propria lymphocytes from mouse intestines[J ] . STAR Protoc, 2022, 3(2): 101366. DOI: 10.1016/j.xpro.2022.101366..

IBA T, LEVY J H. Inflammation and thrombosis: roles of neutrophils, platelets and endothelial cells and their interactions in Thrombus formation during sepsis[J]. J Thromb Haemost, 2018, 16(2): 231-241. DOI: 10.1111/jth.13911.

PARK J H, KANG Y H, HWANG S C, et al . Parthenolide has negative effects on in vitro enhanced osteogenic phenotypes by inflammatory cytokine TNF-α via inhibiting JNK signaling[J ] . Int J Mol Sci, 2020, 21(15): 5433. DOI: 10.3390/ijms21155433 ..

HUANG M, CAI S L, SU J Q. The pathogenesis of sepsis and potential therapeutic targets[J]. Int J Mol Sci, 2019, 20(21): 5376. DOI: 10.3390/ijms20215376.

ZHANG Z, ZHANG K, ZHANG M, et al . Parthenolide suppresses T helper 17 and alleviates experimental autoimmune encephalomyelitis[J ] . Front Immunol. 2022;13: 856694. DOI: 10.3389/fimmu.2022.856694.

KONG F C, ZHANG J Q, ZENG C, et al . Inhibitory effects of parthenolide on the activity of NF-κB in multiple myeloma via targeting TRAF6[J ] . J Huazhong Univ Sci Technolog Med Sci, 2015, 35(3): 343-349. DOI: 10.1007/s11596-015-1435-0.

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