三七皂苷R1不同给药方式对皮肤创伤愈合作用的影响

Effects of notoginsenoside R1 on cutaneous wound healing in mice through different ways of administration

目的研究不同给药方式给予三七皂苷R1对小鼠皮肤创伤愈合的影响。方法采用小鼠皮肤创伤模型,经灌胃(ig)、腹腔注射(ip)、皮肤给药(tdd)3种方式给予三七皂苷R1(30 mg·kg^(-1)),每日1次,持续14 d。隔天拍照并计算伤口愈合率。腹腔注射组造模后d 1、3、7采集伤口皮肤组织,HE染色观察伤口病理变化;ELISA法检测伤口组织中TNF-α、IL-1β、VCAM-1、ICAM-1的表达;实时定量RT-PCR方法检测伤口中COL1A1、COL3A1、TGF-β1、PDGF、VEGF的m RNA表达。结果伤口面积统计结果显示,3种方式给予三七皂苷R1均有效促进小鼠皮肤伤口愈合,腹腔注射组更为明显;HE染色结果显示,三七皂苷R1能有效促进创伤边缘肉芽组织生长,加速胶原纤维的形成,减少炎症细胞浸润;ELISA结果显示,三七皂苷R1能有效降低组织中多种炎症因子蛋白表达;实时定量RT-PCR结果显示,三七皂苷R1对生长因子TGF-β1、PDGF、VEGF的m RNA表达有上调作用。结论在3种不同给药方式中,腹腔注射给予三七皂苷R1对抑制伤口炎症反应、促进皮肤伤口愈合作用最强。

Aim To study the effects of notoginsenoside R1 on cutaneous wound healing in mice through different ways of administration. Methods The cutaneous wound models were operated on the back of the ICR mice by punch. Then 30 mg·kg^（-1） of notoginsenoside R1 was given by intragastric administration（ ig）,intraperitoneal injection（ip） and transdermal delivery（ tdd）. Each group was injected once a day and lasted totally 14 days. Photos were taken for the cutaneous wound of each group on day 0,day 1,day 3,day 5,day 7,day 9,day 11,day 13 and day 14,respectively. The tissues of back skin around the wound were collected on day 1,day 3 and day 7. The growth of granulation tissue,collagen fiber formation and inflammatory cell infiltration in cutaneous wound edge were observed by HE. ELISA was used to detect the protein expression of tumor necrosis factor-alpha（ TNF-α）,interleukin-1 beta（ IL-1β）, vascular cell adhesion molecule-1（ VCAM-1） and intercellular cell adhesion molecule-1（ ICAM-1）. The real-time RT-PCR was used to detect m RNA expression levels of collagen type I alpha 1 chain（ COL1 A1）,collagen type Ⅲ alpha 1 chain（ COL3 A1）,transforming growth factor-beta 1（ TGF-β1）,platelet derived growth factor（ PDGF）and vascular endothelial growth factor（ VEGF） in wounds. Results Notoginsenoside R1 with these different ways of administration was effective in promoting cutaneous wound healing in mice,and the effect of intraperitoneal injection was more significant, as was shown in wound area（ % of Day 0） analysis. HE staining showed that notoginsenoside R1 could promote the growth of granulosa tissue,accelerate the formation of collagen fibers and reduce the infiltration of inflammatory cells. ELISA results indicated that notoginsenoside R1 effectively reduced the protein expression of various inflammatory factors in wound tissues. Realtime RT-PCR results showed that notoginsenoside R1 markedly up-regulated the m RNA levels of various growth factors,including TGF-β1,PDGF and VEGF.Conclusions Intraperitoneal injection of notoginsenoside R1 shows potent effects on inhibiting inflammation around the wound. Thus,intraperitoneal injection is the best among these different ways of notoginsenoside R1 administration which could promote cutaneous wound healing.