Effect and mechanisms of Polygonatum kingianum (polygonati rhizome) on wound healing in diabetic rats.
Effect and mechanisms of Polygonatum kingianum (polygonati rhizome) on wound healing in diabetic rats.
复制标题
DOI：
10.1016/j.jep.2022.115612
复制
发表时间：
2022-08
影响因子：
5.4
通讯作者：
Pan-Yue Qin;Ya-Jing Xu;Xiang-Duo Zuo;Jun-Hua Duan;Qiu Bin;Xue-Fang Li;Jing-Ping Li;Yu Jie
中科院分区：
文献类型：
--
作者：
Pan-Yue Qin;Ya-Jing Xu;Xiang-Duo Zuo;Jun-Hua Duan;Qiu Bin;Xue-Fang Li;Jing-Ping Li;Yu Jie
民族药理学相关性糖尿病皮肤病是糖尿病最严重和最常见的并发症之一。研究发现，高血糖会导致糖代谢异常。葡萄糖增加引起的皮肤微环境污染和晚期糖基化终产物沉积介导的氧化应激可导致隐形皮肤损伤，它们之间的相互作用是导致糖尿病大鼠皮肤伤口难以愈合的关键因素。因此，促进愈合的主要任务是降低血糖水平，缓解晚期糖基化终末产物的沉积。 【摘要】：黄精(PolygonatumkingianumCollett&Hemsl,PK)为天冬科植物,产于中国云南,是白族、哈尼族、佤族等民族防治糖尿病的传统药物。本研究目的研究PK提取物对糖尿病大鼠皮肤创面愈合的影响,探讨PK对创面微环境污染、抗氧化应激信号通路及创面皮肤组织潜在损伤的调节机制。灌胃PK提取物4周，再继续灌胃2周，观察并计算伤口愈合率。采用扫描电镜观察创面边缘皮肤组织的病理形态变化。 Western blotting用于检测蛋白表达。免疫组化检测CD34、AGEs、bFGF、VEGF的表达。采用荧光定量PCR检测皮肤组织中Nrf2/HO-1信号通路。采用试剂盒检测血清生化指标和炎性细胞因子水平。结果PK治疗后，DM病灶大鼠创面愈合率显着提高（P<0.001），皮肤组织炎症细胞浸润减少，新生血管数量增多，表皮和真皮增厚。皮肤中葡萄糖、AGEs、RAGE蛋白和RAGE mRNA含量显着降低（P<0.05、P<0.01、P<0.001），而Nrf2 mRNA、HO-1 mRNA、CD34、bFGF和VEGF表达显着升高（P<0.05、P<0.01、P<0.001）。皮肤中SOD、GSH、MMP-9、MMP-2水平降低(P<0.05,P<0.01,P<0.001),TIMP-2水平升高(P<0.001)。血浆中GSP、GHb、ICAM-1降低（P<0.05、P<0.01、P<0.001），T-AOC、SOD、FINS升高（P<0.05、P<0.01）。血浆和创面皮肤组织中MDA、TNF-、IL-6、IL-2、IFN-γ水平降低（P<0.05、P<0.01、P<0.001）。结论PK可减少创面边缘皮肤组织中炎症细胞浸润和葡萄糖含量，减少皮肤和血浆中炎症因子，增加血管生成，从而提高创面愈合率。 PK可缓解糖尿病大鼠体内AGEs和糖代谢紊乱造成的微环境污染，并通过Nrf 2/HO-1信号通路诱导抗氧化活性，从而减少氧化损伤，抵消内源性皮肤损伤和隐性损伤。
Ethnopharmacological relevanceDiabetic dermatopathy is one of the most serious and common complications of diabetes. It has been found that high glucose can lead to abnormal glycometabolism. The skin microenvironment pollution caused by the increase in glucose and the oxidative stress mediated by the deposition of advanced glycation end products can lead to invisible skin injury, and the interaction between them is the key factor that makes the skin wounds of diabetic rats difficult to heal. Therefore, the main task of promoting healing is to reduce blood glucose levels and relieve the deposition of advanced glycation end products. PolygonatumkingianumCollett & Hemsl (PK) of Asparagaceae is planted in Yunnan, China, and is used by the Bai, Hani and Wa nationalities as a traditional medicine for preventing and treating diabetes.Aim of the studyTo study the effects of PK extract on skin wound healing in diabetic rats and to explore the regulatory mechanism of PK on wound microenvironment pollution, the antioxidative stress signaling pathway and latent injury of wound skin tissue.MethodsFirst, wounds were prepared after diabetic rats were given PK extract by gavage for 4 weeks, and then gavage was continued for 2 weeks to observe and calculate the wound healing rate. A scanning electron microscope was used to observe the pathomorphological changes in the skin tissue at the edge of the wound. Western blotting was used to detect protein expression. Immunohistochemistry was used to detect the expression of CD34, AGEs, bFGF and VEGF. The Nrf2/HO-1 signaling pathway in skin tissue was detected by fluorescence quantitative PCR. Serum biochemical indicators and inflammatory cytokine levels were detected by a kit.ResultsAfter PK treatment, the wound healing rate increased significantly (P< 0.001), the infiltration of inflammatory cells in skin tissue of DM lesion rats decreased, the number of new blood vessels increased, and the epidermis and dermis thickened. The content of glucose, AGEs, RAGE protein and RAGE mRNA in skin decreased significantly (P< 0.05,P< 0.01,P< 0.001), while the expression of Nrf2 mRNA, HO-1 mRNA, CD34, bFGF and VEGF increased significantly (P< 0.05,P< 0.01,P< 0.001). The levels of SOD, GSH, MMP-9 and MMP-2 in skin decreased (P< 0.05,P< 0.01,P< 0.001), but the level of TIMP-2 increased (P< 0.001). GSP, GHb and ICAM-1 in plasma decreased (P< 0.05,P< 0.01,P< 0.001), while T-AOC, SOD and FINS increased (P< 0.05,P< 0.01). The levels of MDA, TNF-, IL-6, IL-2 and IFN-γ in plasma and wound skin tissue decreased (P< 0.05,P< 0.01,P< 0.001).ConclusionPK can reduce the infiltration of inflammatory cells and glucose content in the skin tissue at the edge of the wound, reduce inflammatory factors in skin and plasma, and increase angiogenesis, thus improving the wound healing rate. PK can alleviate the microenvironment pollution caused by AGEs and glucose metabolism disorder in diabetic rats and induce antioxidant activity through the Nrf 2/HO-1 signaling pathway, thus reducing oxidative damage and offsetting endogenous skin damage and hidden damage.