老鹳草素对LPS诱导的小鼠急性肺损伤的影响及机制研究

王静; 李雪; 朱庆林; 王文婷; 李宛蓉; 江仁义; 黄蒙蒙; 郜静欣; 尹陈晨

doi:10.16016/j.2097-0927.202204188

您当前的位置：

首页 >

文章列表页 >

老鹳草素对LPS诱导的小鼠急性肺损伤的影响及机制研究

基础医学 | 更新时间：2026-01-09

- 老鹳草素对LPS诱导的小鼠急性肺损伤的影响及机制研究
- Effect of geraninn on acute lung injury induced by lipopolysaccharide in mice
- 陆军军医大学学报 2022年44卷第22期页码：2300-2306
- 作者机构：
  
  234000 安徽宿州, 安徽省宿州市宿州学院生物与食品工程学院
- 作者简介：
  
  [王静，E-mail: 919706556@qq.com WANG Jing, E-mail: 919706556@qq.com
- 基金信息：
  
  安徽省创新训练项目(S202010379065);安徽省自然科学基金青年项目(2208085QH261);宿州学院科研平台开放课题(2020ykf19)
- DOI：10.16016/j.2097-0927.202204188
  中图分类号： R285.5;R392.32;R563
- 收稿：2022-04-25，
  
  修回：2022-05-18，
  
  纸质出版：2022-11-30
- 稿件说明：
移动端阅览
王静, 李雪, 朱庆林, 等. 老鹳草素对LPS诱导的小鼠急性肺损伤的影响及机制研究[J]. 陆军军医大学学报, 2022,44(22):2300-2306.

Jing WANG, Xue LI, Qinglin ZHU, et al. Effect of geraninn on acute lung injury induced by lipopolysaccharide in mice[J]. Journal of Army Medical University, 2022, 44(22): 2300-2306.
王静, 李雪, 朱庆林, 等. 老鹳草素对LPS诱导的小鼠急性肺损伤的影响及机制研究[J]. 陆军军医大学学报, 2022,44(22):2300-2306. DOI： 10.16016/j.2097-0927.202204188.

Jing WANG, Xue LI, Qinglin ZHU, et al. Effect of geraninn on acute lung injury induced by lipopolysaccharide in mice[J]. Journal of Army Medical University, 2022, 44(22): 2300-2306. DOI： 10.16016/j.2097-0927.202204188.

摘要

目的

研究老鹳草素(

geraniin

)对脂多糖(lipopolysaccharide，LPS)诱导的小鼠急性肺损伤(acute lung injury，ALI)的保护作用机制。

方法

48只BALB/c小鼠(雌性，4周龄，18~22g)随机分为空白组(control组)、LPS组、地塞米松组(Dex组，2 mg/kg)、老鹳草素低剂量组(LD组，10 mg/kg)、老鹳草素中剂量组(MD组，20 mg/kg)、老鹳草素高剂量组(HD组，40 mg/kg)，每组8只。空白组和LPS组灌胃生理盐水，地塞米松组灌胃地塞米松，老鹳草素各剂量组灌胃相应剂量的药物，生理盐水与各个受试药物均每日1次，连续3 d。末次给药1 h后，除空白组外的其余各组均鼻内滴注LPS(4 mg/kg)构建急性肺损伤模型。造模6 h后，检测各组小鼠肺湿干(wet-to-dry，W/D)质量比。采用HE染色法观察肺组织的病理学改变，测定血液及肺泡灌洗液(bronchoalveolar lavage fluid，BALF)中炎性细胞数；采用酶联免疫吸附法(ELISA)检测血清及BALF中白细胞介素6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子α(TNF-α)含量；采用免疫组织化学法检测磷酸化核因子-κBp65(p-NF-κBp65)的表达。

结果

与空白组相比，LPS组小鼠肺泡结构破坏、炎性细胞浸润，血清及BALF中IL-6、IL-1β、TNF-α含量、肺W/D比值、BALF中巨噬细胞数目及中性粒细胞数目、肺组织中p-NF-κBp65的相对表达量均显著升高(

0.01)。与LPS组比较，各给药组中的肺组织病理状态明显得到改善；血清及BALF中IL-6、IL-1β、TNF-α含量、肺W/D比值、BALF中巨噬细胞数目及中性粒细胞数目、肺组织中p-NF-κBp65的相对表达量均显著降低(

0.05)。

结论

老鹳草素对小鼠急性肺损伤具有保护作用，其作用机制可能与其抑制p-NF-κBp65表达、从而减少炎症因子IL-6、IL-1β、TNF-α分泌有关。

Abstract

Objective

To explore the protective mechanism of

geraninn

on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice.

Methods

Forty-eight BALB/c mice (female

4 weeks old

18~22 g) were randomly divided into 6 groups (

=8): the blank group(control group)

the LPS group

the dexamethasone group (Dex group

2mg/kg)

the

geraninn

low dose group (LD group

10 mg/kg)

the

geraninn

medium dose group (MD g

ruop

20 mg/kg) and the

geraninn

high dose group (HD group

40 mg/kg). The mice in blank group and LPS group were fed with normal saline

the mice in the Dex group were fed with dexamethasone and the mice in

geraniin

groups were given corresponding dose of drugs. Normal saline and all tested drugs were given once a day for 3 d. In 1 h later after the last administration

the acute lung injury model was established by using intranasal drip of LPS (4 mg/kg) in all groups except the blank group. In 6 h after modeling

the wet-to-dry (W/D) weight ratio of the lung tissues of mice in each group was collected. The pathological changes of lung tissue were observed by HE staining

and the number of inflammatory cells in broncho alveolar lavage fluid (BALF) and blood was measured; The levels of interleukin-6 (IL-6)

interleukin-1β and tumor necrosis factor α (TNF-α) in plasma and BALF were detected by ELISA. The amount of p-NF-κBp65 was detected by immunohistochemical method.

Results

Compared with the blank group

the alveolar structure in LPS group was destroyed

inflammatory cell infiltrated

and the contents of IL-6

IL-1β and TNF-α in serum and BALF in the LPS group increased; The W/D weight ratio of the lung tissues

the number of macrophages and neutrophils in BALF and serum

the relative expression of p-NF-κBp65 in lung tissue also increased(

0.01). Compared with the LPS group

pathological state of the lung tissues improved obviously among the groups (except the blank group); The contents of IL-6

IL-1β

TNF-α in the serum and BALF

the W/D ratio of the lung tissues

the numbers of macrophages and neutrophils in BALF and the relative expression of p-NF-κBp65 of the lung tissue decreased evidently(

0.05).

Conclusion

Geraninn

has a protective effect on acute lung injury in mice

and its mechanism may be related to the effect that

geraninn

lead

s to repression of p-NF-κB p65 and reduces the expression of inflammatory factors (IL-6

IL-1β and TNF-α).

关键词

Keywords

references

BELLANI G, PHAM T, LAFFEY J, et al . Incidence of acute respiratory distress syndrome: reply[J ] . JAMA, 2016, 316(3): 347. DOI: 10.1001/jama.2016.6471.

BAO H, GAO F Y, XIE G G, et al . Angiotensin-converting enzyme 2 inhibits apoptosis of pulmonary endothelial cells during acute lung injury through suppressing miR-4262[J ] . Cell Physiol Biochem, 2015, 37(2): 759-767. DOI: 10.1159/000430393.

JIA H P, SODHI C P, YAMAGUCHI Y, et al . Pulmonary epithelial TLR4 activation leads to lung injury in neonatal necrotizing enterocolitis[J ] . J Immunol, 2016, 197(3): 859-871. DOI: 10.4049/jimmunol.1600618.

ROCCO P R M, NIEMAN G F. ARDS: what experimental models have taught us[J]. Intensive Care Med, 2016, 42(5): 806-810. DOI: 10.1007/s00134-016-4268-9.

JIANG K F, GUO S, YANG C, et al . Barbaloin protects against lipopolysaccharide (LPS)-induced acute lung injury by inhibiting the ROS-mediated PI3K/AKT/NF-κB pathway[J ] . Int Immunopharmacol, 2018, 64: 140-150. DOI: 10.1016/j.intimp.2018.08.023.

李倩, 买吾拉江·阿不都热衣木, 徐芳, 等. 老鹳草素药理研究进展[J]. 中国中医药信息杂志, 2016, 23(8): 125-128. DOI: 10.3969/j.issn.1005-5304.2016.08.034.

LI Q, ABUDUREYIMU M W L J, XU F, et al . Research progress in pharmaceutical activities of geraniin [J ] . Chin J Inf Tradit Chin Med, 2016, 23(8): 125-128. DOI: 10.3969/j.issn.1005-5304.2016.08.034..

KANG K A, LEE I K, ZHANG R, et al . Radio protective effect of geraniin via the inhibition of apoptosis triggered by γ-radiation-induced oxidative stress[J ] . Cell Biol Toxicol, 2011, 27(2): 83-94. DOI: 10.1007/s10565-010-9172-4..

LI J Y, HUANG H, FENG M Q, et al . In vitro and in vivo anti-hepatitis B virus activities of a plant extract from Geranium carolinianum L[J ] . Antiviral Res, 2008, 79(2): 114-120. DOI: 10.1016/j.antiviral.2008.03.001..

曹志敏, 唐明美, 文强, 等. 内毒素所致急性肺损伤动物模型的研究进展[J]. 实验动物科学, 2017, 34(1): 62-65, 70. DOI: 1006-6179(2017)01-0062-04.

CAO Z M, TANG M M, WEN Q, et al . Research progress of endotoxin-induced ALI models[J ] . Lab Animal Sci, 2017, 34(1): 62-65, 70. DOI: 1006-6179(2017)01-0062-04.

刘畅, 程晓丹, 孙家安, 等. 绿原酸通过调控miR-223/NLRP3轴减轻脂多糖诱导的小鼠急性肺损伤的机制[J]. 中南大学学报(医学版), 2022, 47(3): 280-288. DOI: 10.11817/j.issn.1672-7347.2022.240248.

LIU C, CHENG X D, SUN J A, et al . Mechanism of chlorogenic acid reducing lipopolysaccharide-induced acute lung injury in mice by regulating miR-223/NLRP3 axis[J ] . J Central South Univ Med Sci, 2022, 47(3): 280-288. DOI: 10.11817/j.issn.1672-7347.2022.240248.

秦臻, 汪勃, 谭赵霞, 等. 姜黄素抑制TLR4/HMGB1通路保护脂多糖诱导急性肺损伤的作用[J]. 中国胸心血管外科临床杂志, 2020, 27(6): 685-688. DOI: 10.7507/1007-4848.202002050.

QIN Z, WANG B, TAN Z X, et al . Curcumin inhibits toll-like receptor 4/high mobility group box 1 pathway to protect lipopolysaccharide-induced acute lung injury[J ] . Chin J Clin Thorac Cardiovasc Surg, 2020, 27(6): 685-688. DOI: 10.7507/1007-4848.202002050.

邱建磊. 谷氨酰胺对机械通气肺损伤的保护作用及机制[D]. 济南: 山东大学, 2018.

QIU J L. Theprotective effect and mechanisms of glutamine on ventilator-induced lung injury[D]. Jinan: Shandong University, 2018.

BRACKETT D J, LERNER M R, LACQUEMENT M A, et al . A synthetic lipopolysaccharide-binding peptide based on the neutrophil-derived protein CAP37 prevents endotoxin-induced responses in conscious rats[J ] . Infect Immun, 1997, 65(7): 2803-2811. DOI: 10.1128/iai.6 5.7.2803-2811.1997.

WANG J, LIU Y T, XIAO L, et al . Anti-inflammatory effects of apigenin in lipopolysaccharide-induced inflammatory in acute lung injury by suppressing COX-2 and NF-kB pathway[J ] . Inflammation, 2014, 37(6): 2085-2090. DOI: 10.1007/s10753-014-9942-x.

BAYSTON K F, COHEN J. Bacterial endotoxin and current concepts in the diagnosis and treatment of endotoxaemia[J]. J Med Microbiol, 1990, 31(2): 73-83. DOI: 10.1099/00222615-31-2-73.

MENDEN H, WELAK S, COSSETTE S, et al . Lipopolysaccharide (LPS)-mediated angiopoietin-2-dependent autocrine angiogenesis is regulated by NADPH oxidase 2 (Nox2) in human pulmonary microvascular endothelial cells[J ] . J Biol Chem, 2015, 290(9): 5449-5461. DOI: 10.1074/jbc.M114.600692.

RAHMAN I, SKWARSKA E, MACNEE W. Attenuation of oxidant/antioxidant imbalance during treatment of exacerbations of chronic obstructive pulmonary disease[J]. Thorax, 1997, 52(6): 565-568. DOI: 10.1136/thx.52.6.565.

DUANY L, LEAROYD J, MELITON A Y, et al . Inhibition of Pyk2 blocks lung inflammation and injury in a mouse model of acute lung injury[J ] . Respir Res, 2012, 13(1): 4. DOI: 10.1186/1465-9921-13-4.

WANG J, MA C H, WANG S M. Effects of acteoside on lipopolysaccharide-induced inflammation in acute lung injury via regulation of NF-κB pathway in vivo and in vitro [J ] . Toxicol Appl Pharmacol, 2015, 285(2): 128-135. DOI: 10.1016/j.taap.2015.04.004..

LI Y C, YEH C H, YANG M L, et al . Luteolin suppresses inflammatory mediator expression by blocking the Akt/NFκB pathway in acute lung injury induced by lipopolysaccharide in mice[J ] . Evid Based Complement Alternat Med, 2012, 2012: 383608. DOI: 10.1155/2012/383608.

DOLINAY T, KIM Y S, HOWRYLAK J, et al . Inflammasome-regulated cytokines are critical mediators of acute lung injury[J ] . Am J Respir Crit Care Med, 2012, 185(11): 1225-1234. DOI: 10.1164/rccm.201201-0003OC.

YOSHINARI D, TAKEYOSHI I, KOIBUCHI Y, et al . Effects of a dual inhibitor of tumor necrosis factor-alpha and interleukin-1 on lipopolysaccharide-induced lung injury in rats: involvement of the p38 mitogen-activated protein kinase pathway[J ] . Crit Care Med, 2001, 29(3): 628-634. DOI: 10.1097/00003246-200103000-00029.

SUSANTITAPHONG P, PERIANAYAGAM M C, TIGHIOUART H, et al . Tumor necrosis factor alpha promoter polymorphism and severity of acute kidney injury[J ] . Nephron Clin Pract, 2013, 123(1/2): 67-73. DOI: 10.1159/000351684.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

SIRT3在肺泡Ⅱ型上皮细胞氧化应激及线粒体生物合成中的作用及机制研究

右美托咪定预处理周细胞增强细胞治疗对脓毒症小鼠急性肺损伤的保护作用

靶向抗ICAM-1的载伊马替尼和液态氟碳脂质体对内毒素诱导的急性肺损伤/急性呼吸窘迫综合征模型小鼠的治疗研究

小鼠急性肾损伤致远端肺凋亡和程序性坏死的时程变化

隐丹参酮减轻LPS诱导的ARDS小鼠早期肺纤维化及机制研究