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自体条件血清通过抑制STING通路激活对糖尿病小鼠伤口愈合的影响

Effect of Application of Autologous Conditioned Serum on Wound Healing in Diabetic Mice Through Inhibition of STING Pathway Activation.

作者信息

Li Hongxia

机构信息

Blood Transfusion Department, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China.

出版信息

Biochem Genet. 2025 Feb;63(1):623-633. doi: 10.1007/s10528-024-10734-4. Epub 2024 Mar 13.

DOI:10.1007/s10528-024-10734-4
PMID:38478149
Abstract

Slow wound healing in diabetic patients is a common complication of diabetes. Autologous conditioned serum (ACS) therapy is an emerging and safe biological therapy, and may accelerate the wound healing in diabetes. To investigate the effect of ACS in promoting wound healing in diabetic mice and its possible mechanism. Twenty-four six-week-old male C57BL/6 J mice were selected and divided into 5 groups, including control group (Ctrl), diabetic wound group (DW), ACS treatment group (DW+ACS) and STING pathway validation group (DW+ACS+DMXAA), with six mice in each group. Intervention was initiated after the back incision was performed, and wound healing was assessed on day 0, day 7, and day 14, and wound healing was assessed by hematoxylin and eosin (HE) staining of skin tissue on day 14. At the same time, the wound healing of the fibroblast markers collagen I and α-SMA was measured by immunohistochemistry and western blot. ACS treatment significantly accelerated the diabetic wound according to the wound area and HE staining results. Meanwhile, collagen I and α-SMA concentration evaluated by immunohistochemistry and western blot were remarkably elevated under the ACS interference. The STING signaling pathway was obviously activated in diabetic wound tissues. After the addition of DMXAA, an agonist of STING, the healing function of ACS was dramatically reversed. The application of ACS promotes wound healing in diabetic mice by enhancing fibroblasts. Meanwhile, the STING signaling pathway was inactivated by ACS interference. Hence, ACS can be used in the treatment of wound healing of Diabetes.

摘要

糖尿病患者伤口愈合缓慢是糖尿病常见的并发症。自体条件血清(ACS)疗法是一种新兴且安全的生物疗法,可能会加速糖尿病患者的伤口愈合。为了研究ACS促进糖尿病小鼠伤口愈合的效果及其可能机制。选取24只六周龄雄性C57BL/6 J小鼠,分为5组,包括对照组(Ctrl)、糖尿病伤口组(DW)、ACS治疗组(DW+ACS)和STING通路验证组(DW+ACS+DMXAA),每组6只。背部切口后开始干预,在第0天、第7天和第14天评估伤口愈合情况,并在第14天通过苏木精-伊红(HE)染色皮肤组织评估伤口愈合情况。同时,通过免疫组织化学和蛋白质印迹法检测成纤维细胞标志物I型胶原蛋白和α-平滑肌肌动蛋白(α-SMA)的伤口愈合情况。根据伤口面积和HE染色结果,ACS治疗显著加速了糖尿病伤口的愈合。同时,在ACS干预下,通过免疫组织化学和蛋白质印迹法评估的I型胶原蛋白和α-SMA浓度显著升高。糖尿病伤口组织中STING信号通路明显激活。添加STING激动剂DMXAA后,ACS的愈合功能显著逆转。ACS的应用通过增强成纤维细胞促进糖尿病小鼠伤口愈合。同时,ACS干扰使STING信号通路失活。因此,ACS可用于治疗糖尿病伤口愈合。

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