Role and mechanism of LMO7 in doxorubicin‑induced cardiac dilatation

DING Kehan; WANG Le; YU Wenjun; LI Yang; WANG Chenyang; ZHAO Jinping

doi:10.14188/j.1671-8852.2024.0191

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Role and mechanism of LMO7 in doxorubicin‑induced cardiac dilatation

更新时间：2026-11-05

- Role and mechanism of LMO7 in doxorubicin‑induced cardiac dilatation
- Medical Journal of Wuhan University Vol. 46, Issue 6, Pages: 716-722(2025)
- 作者机构：
  
  武汉大学中南医院心血管外科/心脏大血管外科微创诊疗湖北省工程研究中心/武汉市结构性心脏病微创诊疗临床医学研究中心湖北武汉 430071
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0191
  CLC： R654.2
- Received：20 March 2024，
  
  Published：25 June 2025
- 稿件说明：
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丁柯晗,王乐,余文军等.LMO7在阿霉素诱导的心脏扩张中的作用及机制[J].武汉大学学报（医学版）,2025,46(06):716-722.

DING Kehan,WANG Le,YU Wenjun,et al.Role and mechanism of LMO7 in doxorubicin‑induced cardiac dilatation[J].Medical Journal of Wuhan University,2025,46(06):716-722.
丁柯晗,王乐,余文军等.LMO7在阿霉素诱导的心脏扩张中的作用及机制[J].武汉大学学报（医学版）,2025,46(06):716-722. DOI： 10.14188/j.1671-8852.2024.0191.

DING Kehan,WANG Le,YU Wenjun,et al.Role and mechanism of LMO7 in doxorubicin‑induced cardiac dilatation[J].Medical Journal of Wuhan University,2025,46(06):716-722. DOI： 10.14188/j.1671-8852.2024.0191.

摘要

目的

探讨LMO7在阿霉素诱导的心脏扩张中导致心肌细胞凋亡的作用及机制，为阿霉素（DOX）心脏毒性的改善提供新思路。

方法

使用8周龄雄性小鼠，随机分为两组（

=7），一组腹腔注射4 mg·kg

-1

剂量的DOX构建心脏扩张疾病模型，另一组注射等体积的PBS溶液。5周后进行心脏超声检测后，获取小鼠心脏组织、Masson染色、LMO7免疫组化染色。蛋白印迹法（Western Blot）检测小鼠心脏LMO7、α‑SMA、Collagen Ⅰ、HSPA8、PI3K/p‑PI3K、AKT/p‑AKT的表达。体外实验：使用LMO7敲低腺病毒（Ad‑GFP‑SH LMO7）转染原代心肌细胞，分为对照组和LMO7敲低组。敲低组在不含血清的培养基中利用LMO7敲低腺病毒转染原代心肌细胞，12 h后使用含有1 μmol•L

-1

的DOX培养基（不含血清）换液，继续培养24 h后收取细胞；对照组则使用GFP对照腺病毒原代心肌细胞，步骤相同。检测LMO7、Caspase 9、Caspase 3、BAX/Bcl2、HSPA8、PI3K/p‑PI3K、AKT/p‑AKT的表达。采用

检验分析数据统计学差异。

结果

心脏超声显示相比于对照组小鼠，DOX注射5周后的小鼠心脏功能出现了明显的下降（

0.05），DOX注射小鼠心脏中LMO7、α‑SMA、Collagen Ⅰ、Caspase 9、Caspase 3、BAX/Bcl2表达显著增加（

0.05），免疫组化显示DOX注射组LMO7的含量显著高于对照组，Masson染色显示DOX注射组小鼠心脏中出现了大量的纤维化；相比于Ctrl组原代心肌细胞，DOX处理的原代心肌细胞中LMO7、Caspase 9、Caspase 3、BAX/Bcl2、HSPA8、p‑PI3K/PI3K、p‑AKT/AKT表达显著增加（

0.05）；使用Ad‑GFP‑SH LMO7敲低LMO7后，相比于未敲低组，LMO7、Caspase 9、Caspase 3、BAX/Bcl2

、

表达显著降低（

0.05），HSPA8、p‑PI3K/PI3K、p‑AKT/AKT表达显著上升（

0.05）。

结论

LMO7的敲减会抑制阿霉素诱导的心脏扩张，其潜在机制可能是通过降低HSPA8含量来抑制PI3K‑AKT通路活化。

Abstract

Objective

To investigate the role and mechanism of LMO7 in myocardial cell apoptosis in doxorubicin (DOX)‑induced cardiac dilatation

and to provide new ideas for improving the cardiotoxicity of DOX.

Methods

Eight‑week‑old male mice were randomly divided into two groups (

=7): One group was intraperitoneally injected with 4 mg·kg

-1

DOX to establish a dilated heart disease model(DOX injection group)

and the other group was injected with the same volume of PBS solution(control group). After 5 weeks

cardiac ultrasound was performed

and mouse heart tissues were collected for Masson staining and LMO7 immunohistochemical staining. Western Blot was used to detect the expression of LMO7

α‑SMA

Collagen Ⅰ

HSPA8

PI3K/p‑PI3K

and AKT/p‑AKT in mouse hearts.

In vitro

experiments: primary cardiomyocytes were transfected using LMO7 knockdown adenovirus (Ad⁃GFP⁃SH LMO7) and divided into control and LMO7 knockdown groups. In the knockdown group

primary cardiomyocytes were transfected with LMO7 knockdown adenovirus in serum⁃free medium for 12 h. After 12 h

the cells

were exchanged with DOX medium (serum⁃free) containing 1 μmol•L

-1

and the cells were harvested after 24 h of further incubation; in the control group

the primary cardiomyocytes were transfected with the GFP⁃control adenovirus using the same procedure. The expression of LMO7

Caspase 9

Caspase 3

BAX/Bcl2

HSPA8

PI3K/p‑PI3K

and AKT/p‑AKT was detected. Statistical analysis of the data was performed using a t‑test to analyze the statistical differences.

Results

The cardiac ultrasound revealed a significant decrease in cardiac function in mice after 5 weeks of DOX injection as compared with the control group (

0.05). The expression of LMO7

α‑SMA

Collagen Ⅰ

Caspase 9

Caspase 3

and BAX/Bcl2 in the hearts of the DOX injection group increased significantly (

0.05). Immunohistochemistry showed that the content of LMO7 in the DOX injection group was significantly higher than that in the control group. Masson's staining revealed extensive fibrosis in the hearts of mice in the DOX injection group. Compared with those in the control group

the expression of LMO7

Caspase 9

Caspase 3

BAX/Bcl2

HSPA8

p‑PI3K/PI3K

and as compared with those in the non‑knockdown cardiomyocyte ‑AKT/AKT increased significantly in primary cardiomyocytes of the DOX injection group (

0.05). After knocking down LMO7 using Ad‑GFP‑SH LMO7

the expression of LMO7

Caspase 9

Caspase 3

and BAX/Bcl2 significantly decreased(

0.05)

while the expression of HSPA8

p‑PI3K/PI3K

and p‑AKT/AKT significantly increased (

0.05).

Conclusion

Knockdown of LMO7 inhibits doxorubicin‑induced cardiac dilation

and its potential mechanism may involve reducing HSPA8 content to inhibit PI3K‑AKT pathway activation.

关键词

Keywords

references

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