木犀草素通过激活SIRT1减轻脓毒性心脏损伤

刘彬; 龙军; 司良毅

doi:10.16016/j.2097-0927.202202048

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木犀草素通过激活SIRT1减轻脓毒性心脏损伤

基础医学 | 更新时间：2026-01-09

- 木犀草素通过激活SIRT1减轻脓毒性心脏损伤
- Luteolin alleviates sepsis-induced cardiac injury by activating SIRT1
- 陆军军医大学学报 2022年44卷第21期页码：2165-2173
- 作者机构：
  
  401120 重庆，重庆医科大学附属第三医院心血管疾病中心
- 作者简介：
  
  [司良毅，E-mail：650273@hospital.cqmu.edu.cnSI Liangyi, E-mail: 650273@hospital.cqmu.edu.cn
- 基金信息：
- DOI：10.16016/j.2097-0927.202202048
  中图分类号： R285.5;R541;R631.2
- 收稿：2022-02-14，
  
  修回：2022-04-25，
  
  纸质出版：2022-11-15
- 稿件说明：
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刘彬, 龙军, 司良毅. 木犀草素通过激活SIRT1减轻脓毒性心脏损伤[J]. 陆军军医大学学报, 2022,44(21):2165-2173.

Bin LIU, Jun LONG, Liangyi SI. Luteolin alleviates sepsis-induced cardiac injury by activating SIRT1[J]. Journal of Army Medical University, 2022, 44(21): 2165-2173.
刘彬, 龙军, 司良毅. 木犀草素通过激活SIRT1减轻脓毒性心脏损伤[J]. 陆军军医大学学报, 2022,44(21):2165-2173. DOI： 10.16016/j.2097-0927.202202048.

Bin LIU, Jun LONG, Liangyi SI. Luteolin alleviates sepsis-induced cardiac injury by activating SIRT1[J]. Journal of Army Medical University, 2022, 44(21): 2165-2173. DOI： 10.16016/j.2097-0927.202202048.

摘要

目的

探究木犀草素(luteolin，LTN)改善脓毒性心脏损伤的作用与机制。

方法

采用盲肠结扎穿孔术(caecal ligation perforation

CLP)建立小鼠脓毒症模型，将42只小鼠按随机数字表法分为3组：Sham组、CLP组和CLP+LTN组，每组14只。评估48 h生存情况，使用超声检测心脏功能，Western blot检测SIRT1、p-p65、p65的表达变化，PCR检测炎症因子mRNA表达水平。细胞实验中，使用1 μg/mL LPS处理小鼠巨噬细胞RAW 264.7 12 h，并取其培养基处理小鼠心肌细胞HL-1，加入不同浓度的LTN后，分别使用TNF-α ELISA试剂盒和CCK-8法确定最佳LTN处理浓度。敲低RAW 264.7和HL-1细胞SIRT1表达后，Western blot检测蛋白表达，PCR检测炎性因子mRNA水平，商用试剂盒检测ATP含量，CCK-8检测细胞活力。

结果

与Sham组相比，CLP组小鼠48 h生存率、心功能和SIRT1的表达明显降低(

＜0.05)，而p65的磷酸化水平(p-p65/p65)，TNF-α、IL-1、IL-6的mRNA表达水平显著上升(

＜0.05)，但这些效应均可被LTN治疗抵消(

＜0.05)。在RAW 264.7细胞中，LTN处理可以明显改善LPS引起的SIRT1的表达下降，以及p65磷酸化水平和IL-1、TNF-α、IL-6的mRNA表达水平升高(

＜0.05)，但SIRT1敲低则可抵消LTN的作用(

＜0.05)。在HL-1细胞中，LTN处理可显著减少RAW 264.7+LPS培养基(RLM)处理引起的SIRT1表达、ATP含量和细胞活力下降(

＜0.05)，但该作用在敲低SIRT1后被部分消除(

＜0.05)。

结论

LTN可通过激活SIRT1抑制炎症反应，提高心肌细胞抗炎作用，从而减少脓毒性心功能障碍。

Abstract

Objective

To explore the effect and mechanism of luteolin (LTN) in sepsis-induced cardiac injury.

Methods

Caecal ligation perforation (CLP) was used to establish a septic model in mice

and 42 mice were randomly divided into Sham group

CLP group and CLP+LTN group

with 14 mice in each group. The 48-hour survival rate was observed. Ultrasonography was used to detect cardiac function

Western blotting was employed to detect the expression of SIRT1

p-p65 and p65

and PCR was applied to measure the mRNA levels of inflammatory cytokines. In

in vitro

study

LPS of 1 μg/mL was used to treat mouse macrophagocyte RAW 264.7

and then the medium was used to treat mouse cardiomyocytes HL-1. LPS-treated RAW 264.7 cells and RAW 264.7+LPS medium-treated HL-1 cells were co-cultured with different concentrations of LTN

and the optimal LTN concentration was determined by TNF-α ELISA kit and CCK-8 assay. Then after SIRT1 exp

ression of RAW 264.7 cells and HL-1 cells was knocked down by siRNA

the expression of above proteins was detected by Western blotting

and mRNA expression levels of inflammatory cytokines were measured by PCR

ATP content was detected by reagent kit

and cell viability was detected by CCK-8 assay.

Results

The mice of the CLP group had significantly lower 48-hour survival rate

cardiac function and SIRT1 expression (

0.05)

and increased protein level of p-p65/p65 and mRNA levels of IL-1

TNF-α and IL-6 (

0.05) when compared with the Sham group. However

these effects were reversed by LTN treatment (

0.05). In RAW 264.7 cells

LTN treatment significantly reversed LPS-induced decrease of SIRT1 expression

and increases in protein level of p-p65 and mRNA levels of IL-1

TNF-α and IL-6 (

0.05). Nevertheless

SIRT1 knockdown abolished the effect of LTN (

0.05). In HL-1 cells

LTN treatment significantly reversed the decrease of SIRT1 expression

ATP content and cell viability induced by RAW 264.7+LPS medium (

0.05)

but this effect could be partially eliminated by SIRT1 knockdown (

0.05).

Conclusion

LTN can inhibit inflammatory response and enhance the anti-inflammatory effect of cardiomyocytes by activating SIRT1

and thus reduce sepsis-induced cardiac dysfunction.

关键词

Keywords

references

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