Sheng-ji Hua-yu formula promotes diabetic wound healing of re-epithelization via Activin/Follistatin regulation.
Sheng-ji Hua-yu formula promotes diabetic wound healing of re-epithelization via Activin/Follistatin regulation.
复制标题
生肌化瘀方通过激活素/卵泡抑素调节促进糖尿病伤口上皮再生愈合
DOI：
10.1186/s12906-017-2074-8
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发表时间：
2018-01-29
影响因子：
--
通讯作者：
Li FL
中科院分区：
文献类型：
--
作者：
Kuai L;Zhang JT;Deng Y;Xu S;Xu XZ;Wu MF;Guo DJ;Chen Y;Wu RJ;Zhao XQ;Nian H;Li B;Li FL
生肌化瘀方是治疗糖尿病迟发性创面的常用中药之一。然而，阐明三圣化瘀方如何影响糖尿病伤口愈合再上皮化过程中过度炎症的相关分子生物学机制是一个迫切需要完成的任务。本研究的目的是评估促/抗炎因子的非特异性表达对转化生长因子-β（TGF-β）超家族的影响。（激活素和卵泡抑素）在体内糖尿病伤口愈合的再上皮化过程中的作用，并表征激活素/卵泡抑素蛋白表达调节，磷酸化-Smad（pSmad 2），核因子-κ B p50（NF-kB）p50在糖尿病创面愈合中的作用。四肾化瘀方由岳阳市中西医结合医院制剂室配制。通过环形切除伤口模型评价糖尿病伤口愈合活性。通过肉眼评价检查伤口愈合活性。采用真实的时间PCR、Western blot、免疫组化和苏木精-伊红（H&E）染色等方法检测创面组织中活化素/卵泡抑素（Activin/Follistatin）的表达调控、pSmad 2和NF-κ B p50蛋白的表达。肉眼评价分析显示，糖尿病小鼠伤口愈合延迟，四肾化瘀方加快糖尿病小鼠伤口愈合时间。真实的时间PCR分析显示，与正常小鼠伤口相比，糖尿病延迟伤口中激活素/卵泡抑素的mRNA表达更高。Western印迹免疫分析显示损伤后15天通过SJHY配方治疗的激活素/卵泡抑素蛋白水平降低。免疫组织化学研究了创伤后第15天糖尿病SJHY与糖尿病对照小鼠表皮中pSmad 2和NF-κ B p50核染色的减少。H&E染色显示SJHY配方加速糖尿病伤口愈合的再上皮化。本研究发现，糖尿病伤口愈合时间延迟与激活素/卵泡抑素的高表达水平密切相关，从而导致再上皮化过程中的过度炎症。SJHY配方通过降低激活素/卵泡抑素的高表达来加速糖尿病伤口的再上皮化和愈合时间。
Sheng-ji Hua-yu(SJHY) formula is one of the most useful Traditional Chinese medicine (TCM) in the treatment of the delayed diabetic wound. However, elucidating the related molecular biological mechanism of how the SJHY Formula affects excessive inflammation in the process of re-epithelialization of diabetic wound healing is a task urgently needed to be fulfilled. The objectives of this study is to evaluate the effect of antagonisic expression of pro−/anti-inflammatory factors on transforming growth factor-β(TGF-β) superfamily (activin and follistatin) in the process of re-epithelialization of diabetic wound healing in vivo, and to characterize the involvement of the activin/follistatin protein expression regulation, phospho-Smad (pSmad2), and Nuclear factor kappa B p50 (NF-kB) p50 in the diabetic wound healing effects of SJHY formula. SJHY Formula was prepared by pharmaceutical preparation room of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. Diabetic wound healing activity was evaluated by circular excision wound models. Wound healing activity was examined by macroscopic evaluation. Activin/follistatin expression regulation, protein expression of pSmad2 and NF-kB p50 in skin tissue of wounds were analyzed by Real Time PCR, Western blot, immunohistochemistry and hematoxylin and eosin (H&E) staining. Macroscopic evaluation analysis showed that wound healing of diabetic mice was delayed, and SJHY Formula accelerated wound healing time of diabetic mice. Real Time PCR analysis showed higher mRNA expression of activin/follistatin in diabetic delayed wound versus the wound in normal mice. Western Blot immunoassay analysis showed reduction of activin/follistatin proteins levels by SJHY Formula treatment 15 days after injury. Immunohistochemistry investigated the reduction of pSmad2 and NF-kB p50 nuclear staining in the epidermis of diabetic SJHY versus diabetic control mice on day 15 after wounding. H&E staining revealed that SJHY Formula accelerated re-epithelialization of diabetic wound healing. The present study found that diabetic delayed wound healing time is closely related to the high expression level of activin/follistatin, which leads to excessive inflammation in the process of re-epithelization. SJHY Formula accelerates re-epithelialization and healing time of diabetic wounds through decreasing the high expression of activin/follistatin.
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影响因子：
5.1
作者：
Guariguata, L.;Whiting, D. R.;Shaw, J. E.
通讯作者：
Shaw, J. E.
影响因子：
6
作者：
Han, Gangwen;Li, Fulun;Wang, Xiao-Jing
通讯作者：
Wang, Xiao-Jing
影响因子：
3.7
作者：
Noguchi F;Nakajima T;Inui S;Reddy JK;Itami S
通讯作者：
Itami S
影响因子：
3
作者：
Nishikori, Yoriko;Shiota, Naotaka;Okunishi, Hideki
通讯作者：
Okunishi, Hideki
影响因子：
5.1
作者：
Ogurtsova, K.;Fernandes, J. D. da Rocha;Makaroff, L. E.
通讯作者：
Makaroff, L. E.