Epicatechin Reduces Diabetic Vascular Smooth Muscle Aging by Regulating the cGAS-STING-IRF3 Pathway

Author：ZHANG Luwei, LIN Hui, CHEN Zhuang, ZHANG Haiqin, TONG Jie, LI Yuanbin

Unit：Hunan Traditional Chinese Medical College, Zhuzhou Hunan 412012, China

Quote：引用：张露微，林辉，陈壮，张海琴，童洁，李媛彬.表儿茶素通过调节cGAS-STING-IRF3通路减轻糖尿病性血管平滑肌衰老[J].中医药导报,2025,31(1):37-41.

DOI：10.13862/j.cn43-1446/r.2025.01.007

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Abstract：Objective: To explore the effect of epicatechin on vascular smooth muscle aging in diabetic mice and its regulatory mechanism on cGAS-STING-IRF3 pathway. Methods: Diabetic mouse models were established by injecting streptozotocin and high-sugar diet. The successful modeling mice were randomly divided into STZ group, epicatechin group and metformin group, with 10 mice in each group. And another 10 normal mice were selected as control group. Mouse aortic smooth muscle cells were randomly divided into control group, high glucose group, epicatechin group, 2′3′-cGAMP+epicatechin group or RU.521 group to observe the expression of aging-related indicators, cell viability, and pathway-related molecules. Results: Compared with normal control group, the levels of aging-related secreted phenotype factors (IL-6, IL-8, IL-1β, TNF-α), the expression of aging-related proteins (P16, P21) and signaling pathway-related proteins (cGAS, STING, p-IRF3, IRF3) were significantly increased in the STZ group and high glucose group (P<0.05). The cell activity of the high glucose group was significantly reduced (P<0.05), while the positive percentage of SA-β-gal staining was apparently increased (P<0.05). Adding epicatechin treatment could improve the above targets significantly (P<0.05). The STING agonist could reverse the protective effect of epicatechin, while cGAS inhibitors could produce similar effects to epicatechin. Conclusion: Epicatechin can alleviate diabetic vascular smooth muscle cell aging, possibly by inhibiting the cGAS-STING-IRF3 signaling pathway.

Key words：diabetes; epicatechin; vascular smooth muscle aging; cGAS-STING-IRF3 signaling pathway; mice

摘要：目的：探究表儿茶素对糖尿病小鼠血管平滑肌衰老的作用及表儿茶素在该过程中对cGAS-STING-IRF3信号通路的调节机制。方法：采用腹腔注射链脲佐菌素（STZ）及高糖饲养建立糖尿病小鼠模型，将造模成功小鼠随机分为STZ组、表儿茶素组、二甲双胍组，每组10只，另取10只正常小鼠为对照组；将小鼠主动脉平滑肌细胞随机分为对照组、高糖组、表儿茶素组、2′3′-cGAMP+表儿茶素组或RU.521组，观察各组衰老相关指标、细胞存活率以及信号通路相关分子表达情况。结果：与对照组比较，STZ组及高糖组的衰老相关分泌表型因子（IL-6、IL-8、IL-1β、TNF-α）的分泌及衰老相关蛋白（P16、P21）、信号通路相关蛋白（cGAS、STING、p-IRF3、IRF3）的表达明显升高（P<0.05），并且高糖组细胞的细胞活性明显降低（P<0.05）、SA-β-gal染色阳性率明显升高（P<0.05）；加入表儿茶素处理后，上述指标能得到明显改善（P<0.05）。STING激动剂能逆转表儿茶素的保护作用，而cGAS抑制剂能产生与表儿茶素相似的作用。结论：表儿茶素可以减轻糖尿病小鼠血管平滑肌细胞衰老，可能是通过抑制cGAS-STING-IRF3信号通路发挥作用。

关键词：糖尿病；表儿茶素；血管平滑肌衰老；cGAS-STING-IRF3信号通路；小鼠

Release time：2025-11-28

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