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贵州医科大学法医学院/法医司法鉴定中心,贵阳 550004
刘江金,Email:191760377@qq.com,研究方向:法医病理学。
张桥军,Email:540372758@qq.com。
收稿:2024-06-13,
修回:2024-12-08,
录用:2024-12-10,
纸质出版:2025-08-28
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刘江金,张健,王承飞,等.cGAS-STING信号通路在不同程度冠状动脉粥样硬化病变下的表达研究[J].重庆医科大学学报,2025,50(8):1109-1114.
Liu Jiangjin,Zhang Jian,Wang Chengfei,et al.Expression of the cyclic GMP-AMP synthase-stimulator of interferon genes signaling pathway in human coronary atherosclerotic lesions with different degrees of stenosis[J].Journal of Chongqing Medical University,2025,50(8):1109-1114.
刘江金,张健,王承飞,等.cGAS-STING信号通路在不同程度冠状动脉粥样硬化病变下的表达研究[J].重庆医科大学学报,2025,50(8):1109-1114. DOI: 10.13406/j.cnki.cyxb.003789.
Liu Jiangjin,Zhang Jian,Wang Chengfei,et al.Expression of the cyclic GMP-AMP synthase-stimulator of interferon genes signaling pathway in human coronary atherosclerotic lesions with different degrees of stenosis[J].Journal of Chongqing Medical University,2025,50(8):1109-1114. DOI: 10.13406/j.cnki.cyxb.003789.
目的
2
观察不同程度冠状动脉粥样硬化病变下心肌组织的病理改变,检测冠脉内环状鸟嘌呤核苷酸腺嘌呤核苷酸合成酶(cyclic gmp-amp synthase,cGAS)-干扰素基因刺激物(stimulator of interferon genes,STING)信号通路蛋白的表达水平,探讨cGAS-STING在冠心病的发生发展过程中所发挥的作用。
方法
2
筛选符合条件的冠心病案例及对照案例,分5组:冠状动脉正常为对照组,其余4组按照冠脉狭窄程度分别为Ⅰ、Ⅱ、Ⅲ、Ⅳ级分组,常规苏木精伊红染色观察和评估冠脉病理情况、免疫印迹检测冠脉组织内cGAS-STING通路下游蛋白表达水平,Elisa检测冠脉炎症因子水平,并利用相关性分析方法分析cGAS-STING信号通路下游蛋白和炎症因子的表达水平与冠心病发生发展的关系。
结果
2
①与对照组相比,镜下观察到其余4组冠脉呈现不同程度的管壁增厚和管腔狭窄等病理改变且狭窄程度逐级递增;②Ⅰ、Ⅱ、Ⅲ、Ⅳ级冠脉狭窄的冠脉组织中的cGAS-STING信号通路下游蛋白以及炎症因子表达情况较对照组增高且为逐级增高的趋势;③cGAS-STING信号通路下游蛋白在冠脉组织中的表达与冠心病发生发展呈现正相关(cGAS,
r
=0.927,
P
<
0.001;p-Sting,
r
=0.889,
P
<
0.001;p-TBK1,
r
=0.910,
P
<
0.001;p-IRF3,
r
=0.936,
P
<
0.001;IFN-1,
r
=0.936,
P
<
0.001;肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α),
r
=0.945,
P
<
0.001;白细胞介素-1β(interleukin-1 beta,IL-1β),
r
=0.962,
P
<
0.001;白细胞介素-6(interleukin-6,IL-6),
r
=0.933,
P
<
0.001)。
结论
2
cGAS-STING信号通路下游蛋白以及炎症因子的表达水平差异有统计学意义,此信号通路可能可作为治疗冠心病的潜在靶点。
Objective
2
To observe the pathological changes of myocardial tissue under differentdegrees of coronary atherosclerotic lesions,to measure the expression levels of proteins associated with the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in coronary arteries,and to investigate the role of cGAS-STING in the development and progression of coronary heart disease.
Methods
2
Eligible cases of coronary heart disease and control cases were selected and divided into control group with normal coronary arteries and grade Ⅰ,Ⅱ,Ⅲ,and Ⅳ coronary artery stenosis groups. HE staining was used to observe and evaluate the pathological conditions of coronary arteries,Western blotting was used to measure the expression levels of downstream proteins of the cGAS-STING pathway in coronary tissue,and ELISA was used to measure the levels of inflammatory factors in coronary tissue. A correlation analysis was performed to investigate the correlation of the expression levels of downstream proteins of the cGAS-STING signaling pathway and related inflammatory factors with the development and progression of coronary heart disease.
Results
2
Microscopic examination showed that compared with the control group,the other four groups had varying degrees of pathological changes such as vascular wall thickening and luminal stenosis,with a gradual increase in the degree of stenosis from grade Ⅰ to grade Ⅳ coronary lesions. Compared with the control group,the grade Ⅰ,Ⅱ,Ⅲ,and Ⅳ coronary artery stenosis groups had significant increases in the expression levels of downstream proteins of the cGAS-STING signaling pathway and related inflammatory factors in coronary tissue,with a trend of increase from grade Ⅰ to grade Ⅳ coronary lesions. The expression levels of downstream proteins of the cGAS-STING signaling pathway in coronary tissue were positively correlated with the development and progression of coronary heart disease(cGAS:
r
=0.927,
P
<
0.001;p-Sting:
r
=0.889,
P
<
0.001;p-TBK1:
r
=0.910,
P
<
0.001;p-IRF3:
r
=0.936,
P
<
0.001;IFN-1:
r
=0.936,
P
<
0.001;TNF-α:
r
=0.945,
P
<
0.001;IL-1β:
r
=0.962,
P
<
0.001;IL-6:
r
=0.933,
P
<
0.001).
Conclusion
2
There are significant differences in the expression levels of downstream proteins of the cGAS-STING signaling pathway and related inflammatory factors,and this signaling pathway may be a potential target for the treatment of coronary heart disease.
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