基于皮肤“微环境污染”的人参皂苷Rg3修复糖尿病皮肤损伤的作用机理研究

Study on the Mechanism of Ginsenoside Rg3 in Repairing Diabetic Skin Damage Based on Skin "Micro-environmental Pollution"

目的探究人参皂苷Rg3(Ginsenoside Rg3,Rg3)修复糖尿病(diabetes mellitus,DM)皮肤损伤的作用及分子机理。方法雄性SD(Sprague Dawley,SD)大鼠建立DM模型,随机分为正常组、模型组、氨基胍(amino guanidirig,AG)组、人参皂苷Rg3高、低剂组。上述大鼠灌胃4周后背部皮肤等面积全层切除,手术后第21天皮肤创面取材。检测大鼠皮肤中晚期糖基化终末产物(Advanced glycation end products,AGEs)和创面中P物质(Substance P,SP)的表达量;观察皮肤真皮层内胶原分布及相对胶原含量;检测碱性成纤维细胞生长因子(Basic fibroblast growth factor,bFGF)的含量并观察其被糖基化的程度;观察人参皂Rg3对AGEs干预后人脐静脉内皮细胞(HUVEC)的生长情况;同时检测血清中过氧化氢(H_(2)O_(2))、丙二醛(MDA)、谷胱甘肽(GSH)的水平。结果与模型组比较,给予人参皂苷Rg3治疗后:AGEs在皮肤组织中的蓄积较少;SP的含量增加(P<0.05);胶原增多且交织成网;bFGF的表达高于模型组(P<0.01),糖基化程度不明显;HUVEC细胞凋亡率明显下降(P<0.05或P<0.01);血清中H_(2)O_(2)、MDA含量显著下降(P<0.05),GSH含量上升(P<0.05)。结论人参皂苷Rg3对DM大鼠皮肤损伤具有明显修复作用,与临床观察研究结果一致。阐明了人参皂苷Rg3改善DM皮肤“微环境污染”、调节皮肤组织功能异常的“隐形损害”的分子作用机理,可多靶点修复DM皮肤损伤。

Objective To explore the effect and mechanism of ginsenoside Rg3 in repairing diabetic skin injury.Methods Male SD rats were established DM model and randomly divided into normal group, model group,aminoguanidine group, high and low dose Ginsenoside Rg3 groups. After 4 weeks of intragastric administration, the skin of the back was resected with equal area, and the skin samples of the wound were taken on the 21stday after injury. The skin samples were taken to detect the stratification of AGEs and SP in the wound;The distribution of collagen in the dermis was observed and its relative content was detected;The content of bFGF was detected and the degree of glycosylation was observed;the apoptosis rate of HUVEC cells treated with AGEs by Ginsenoside Rg3 was calculated;the levels of H_(2)O_(2), MDA and GSH were detected in serum.Results Compared with the model group, after Ginsenoside Rg3 treatment, the accumulation of AGEs in the skin tissue was less;the content of SP increased(P<0.05);collagen increased significantly and interwoven into a network and the relative content increased;the expression of bFGF was higher than that in the model group(P<0.01);The degree of glycosylation was not obvious;the apoptosis rate of HUVEC cells was significantly decreased(P<0.05 or P<0.01);the contents of H_(2)O_(2) and MDA in serum were significantly decreased(P<0.05), and the content of GSH was increased(P<0.05). Conclusion Ginsenoside Rg3 has obvious repairing effect on skin damage in DM rats, which is consistent with the clinical observation and research results. The molecular mechanism of ginsenoside Rg3 to improve the "microenvironmental pollution" of DM skin and regulate the "invisible damage" of abnormal skin tissue function is elucidated, and it can repair DM skin damage with multiple targets.