【摘要】 目的 在猪全层皮肤切除模型中，观察负载白藜芦醇的猪小肠黏膜下层（small intestine submucosa, SIS）脱细胞基质对创面炎性反应和瘢痕形成的影响，评价愈合质量。方法 自2022年3月至2022年7月，新疆医科大学第一附属医院整形美容外科将SIS脱细胞基质胶和白藜芦醇（resveratrol, Rev）溶液配制成膜片状的负载白藜芦醇的SIS脱细胞基质(Rev/SIS)。取小型猪3只，在每只猪背建立4个4 cm×4 cm的全层皮肤缺损创面，按照不同治疗手段随机分为4组：生理盐水纱布组（对照组）、白藜芦醇组（Rev组）、SIS脱细胞基质组（SIS组）和负载白藜芦醇的SIS脱细胞基质组（Rev/SIS组）。分别记录术后第7、14、21、28天的创面愈合及术后第42天的瘢痕形成状况；采集创缘组织行组织学检查和免疫组化染色分析，评估愈合过程中的炎性浸润和再血管化水平，以及所形成瘢痕组织的皮肤厚度和胶原沉积情况；并分别在术后第3、7天检测各组创面中炎性因子肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、M1型巨噬细胞标志物i NOS和M2型巨噬细胞标志物ARG-1的m RNA相对表达量。结果 术后第7、14、21天，SIS组和Rev/SIS组创面残留率均显著低于对照组（P<0.05），术后第21天Rev/SIS组创面残留率低于SIS组（P<0.001），术后第28天除Rev/SIS组外其余3组创面均未完全愈合；术后第42天Rev/SIS组瘢痕面积最小，质地柔软，扁平且无明显色沉。Rev/SIS组TNF-a、IL-6 m RNA表达量均低于对照组（P<0.05）,3种治疗手段均能降低创面i NOS m RNA表达（P<0.001)，但以Rev/SIS组最为显著（P<0.05），且Rev/SIS组的ARG-1 m RNA表达高于其余3组（P<0.05），该组创面炎性浸润程度最低，再血管化水平最高。其余3组瘢痕的表皮、真皮厚度均低于对照组（P<0.01），也以Rev/SIS组改善最为显著（P<0.0001)，且该组胶原沉积与正常皮肤相似，排列有序。结论 尽管SIS脱细胞基质和白藜芦醇单独使用也可能产生抗炎效应，在促进创面愈合的同时，减少瘢痕形成面积，有效提高愈合质量；但二者联合应用的效果更为显著，Rev/SIS脱细胞基质为开发新型皮肤创面敷料提供了一种潜在选择。更多还原

【Abstract】 Objective To observe the effect of resveratrol loaded Ssmall intestine submucosa(SIS) acellular matrix on wound inflammatory and scar formation in a porcine full-thickness skin resection model, then to evaluate the healing quality. Methods SIS acellular matrixloaded with Resveratrol(Rev/SIS) was prepared by SIS acellular matrix gel and Resveratrol(Rev) solution in the Department of Plastic Surgery of the First Affiliated Hospital of Xinjiang Medical University from March to July in 2022. Three miniature pigs were selected and four wounds of 4 cm×4 cm were made on the back of each pig. According to different treatments, they were randomly divided into4 groups: control group, resveratrol group(Rev), SIS acellular matrix group(SIS) and SIS acellular matrix group loaded with resveratrol(Rev/SIS). Wound healing on day 7, 14, 21, 28 after operation and scar formation on day 42 after operation were recorded. The wound margin tissues were collected for histological examination and immunohistochemical staining analysis, and the levels of inflammatory infiltration and revascularization during the healing process were evaluated, as well as the skin thickness and collagen deposition of the scar. The relative m RNA expression of inflammatory factors TNF-α, IL-6, M1 macrophage marker i NOS and M2 macrophage marker ARG-1 in wounds of each group were detected on day 3 and 7 after operation respectively. Results On day 7, 14 and 21 after operation, the wound residual rate in SIS and Rev/SIS groups was significantly lower than in control group(P<0.05), the wound residual rate in Rev/SIS group was lower than in SIS group on day 21(P<0.001), and the wounds in the other three groups except Rev/SIS group were not completely healed on day28; On day 42, the scar area in Rev/SIS group was the smallest, with soft, flat texture and no obvious color sedimentation. The m RNA expressions of TNF-α and IL-6 in Rev/SIS group were lower than those in control group(P<0.05). The m RNA expression of i NOS in wounds was decreased by all three treatments(P<0.001), with the most significance in Rev/SIS group(P<0.05). The m RNA expression of ARG-1 in Rev/SIS group was higher than in the other three groups(P<0.05), with the slightest inflammatory infiltration and the best revascularization in Rev/SIS group. The epidermic and dermal thickness of scars in the other three groups were lower than in the control group(P<0.01), and the most significant improvement was detected in the Rev/SIS group(P<0.0001). The collagen deposition in Rev/SIS group was similar to the normal skin and arranged in an orderly manner. Conclusion Although SIS acellular matrix and resveratrol may have anti-inflammatory effects alone, which can promote wound healing, reduce the area of scar and improve the healing quality effectively. However, the combination is more effective, the Rev/SIS acellular matrix provides a potential option for the development of new skin wound dressings.更多还原