Objective: To investigate the effect of 5-aminolevulinic(ALA)-photodynamic therapy(PDT) on the expressions of MMP-9, MMP-13 and TIMP-1 of hypertrophic scar model in rabbit ears, and analyze the possible therapeutic me...Objective: To investigate the effect of 5-aminolevulinic(ALA)-photodynamic therapy(PDT) on the expressions of MMP-9, MMP-13 and TIMP-1 of hypertrophic scar model in rabbit ears, and analyze the possible therapeutic mechanisms of ALA-PDT treatment to hypertrophic scars of rabbit ears. Methods: The experimental animals were randomly divided into normal control, negative control, high concentration of ALA-PDT, low concentration of ALA-PDT and PDT groups. The latter three groups received ALA-PDT treatment or PDT treatment once a week for 3 weeks. The specimens of the rabbits were collected respectively 1, 2 and 3 months after treatment to be used for RT-PCR and Western-blot test. Results: 1, 2 and 3 months after PDT treatment, the expressions of MMP-9 and MMP-13(including mRNA and protein) in hypertrophic scar tissues of three treatment groups were significantly higher than those of the negative control group(P<0.01), and the expression of TIMP-1 mRNA and protein of three treatment groups were significantly lower than that of the negative control group(P<0.01). There were also significant differences between high-concentration ALA-PDT treatment group and the low one(P<0.05). Conclusion: ALA-PDT is effective in treating hypertrophic scars of rabbit ears, and its possible therapeutic mechanisms are that ALA-PDT treatment generates oxidation activation effect to activate the activity of MMPs and induces the photoaging of fibroblasts of hypertrophic scar tissues of rabbit ears to inhibit the activity of TIMPs, which causes the up-regulation of MMPs and the down-regulation of TIMPs. Because of this, the degradation of collagen and ECM is accelerated and the formation of scars is suppressed.展开更多
Background:The role of autophagy in the formation of hypertrophic scars(HS)remains unclear.This study aimed to explore the role and potential mechanism of autophagy during the development of HS.Methods:RNA and protein...Background:The role of autophagy in the formation of hypertrophic scars(HS)remains unclear.This study aimed to explore the role and potential mechanism of autophagy during the development of HS.Methods:RNA and protein expression levels of Beclin-1,p62,and LC3II in normal skin tissues and HS specimens from different patients were examined.Autophagy inducers and inhibitors were used to cure established HS in rabbit ears,and the expression of Beclin-1,p62,and LC3II at the RNA and protein level was determined.Lastly,the effects of autophagy inducers and inhibitors on HS development were analyzed.Results:Compared to normal skin tissues,the expression of LC3II and Beclin-1 was higher(P<0.05),while that of p62 was lower(P<0.05)in HS tissues.In addition,the LC3II/LC3I ratio was increased during HS formation,and the altered expression of the three proteins stabilized after one year.Administration of autophagy inducers enhanced the formation of HS as well as the expression levels of LC3II and Beclin-1 but decreased p62 expression.Meanwhile,administration of autophagy inhibitors increased the expression of LC3II,Beclin-1,and p62,along with reduced HS formation.Conclusion:Autophagic activity increased during HS initiation and subsequent stabilization.In addition,autophagy inhibitors were able to inhibit HS formation by suppressing autophagy,whereas autophagy inducers promoted scar hyperplasia by enhancing autophagy。展开更多
目的:他克莫司是临床广泛应用的一种药物,其对增生性瘢痕是否产生作用并无相关报道,为此提出并证实了他克莫司可以抑制兔耳瘢痕增生。方法:建立兔耳增生性瘢痕模型,选10只新西兰大耳白兔双耳腹侧用打孔器制作直径1cm圆形创面,伤后14天...目的:他克莫司是临床广泛应用的一种药物,其对增生性瘢痕是否产生作用并无相关报道,为此提出并证实了他克莫司可以抑制兔耳瘢痕增生。方法:建立兔耳增生性瘢痕模型,选10只新西兰大耳白兔双耳腹侧用打孔器制作直径1cm圆形创面,伤后14天创面上皮化后给药,每只兔左耳为空白对照组涂等剂量凡士林软膏,右耳为他克莫司治疗组。分别在伤后14天、21天2、8天3、5天和49天采集标本,行HE染色,观察形态学差异;Real-t i me PCR检测纤维化相关因子TGF-β1、TGF-β2、Col l agen-α1等的表达。结果:HE染色可见他克莫司组成纤维细胞数量及胶原纤维较对照组明显减少,PCR结果可见TGF-β1、TGF-β2及Col l agen-α1表达较对照组在各时间点均减少。结论:实验组较对照组瘢痕明显减轻,证明他克莫司显著抑制兔耳瘢痕增生,可作为临床上治疗及预防瘢痕增生的全新疗法。展开更多
目的研究二氢青蒿素对兔耳增生性瘢痕增生的影响。方法选取20只成年新西兰大耳白兔建立兔耳增生性瘢痕动物模型,待伤口上皮化后,将其随机分成两组,每组10只。对照组灌胃给予10 m L的生理盐水,实验组灌胃给予10 m L的二氢青蒿素,1次/天,...目的研究二氢青蒿素对兔耳增生性瘢痕增生的影响。方法选取20只成年新西兰大耳白兔建立兔耳增生性瘢痕动物模型,待伤口上皮化后,将其随机分成两组,每组10只。对照组灌胃给予10 m L的生理盐水,实验组灌胃给予10 m L的二氢青蒿素,1次/天,连续给予1周。记录观察术后20 d和50 d 2组兔耳瘢痕的发生和兔耳瘢痕的大小。结果对照组兔耳瘢痕的发生率大于实验组兔耳瘢痕的发生率,差异有统计学意义(P<0.05),表明二氢青蒿素具有降低兔耳瘢痕发生的疗效;对照组兔耳瘢痕大于实验组兔耳瘢痕,差异有统计学意义(P<0.050),表明二氢青蒿素具有治疗兔耳瘢痕的作用。结论二氢青蒿素对兔耳增生性瘢痕具有显著的疗效,作为一种有效的药物,值得对其做进一步的研究。展开更多
基金Supported by the National Natural Science Foundation of China(30901298)
文摘Objective: To investigate the effect of 5-aminolevulinic(ALA)-photodynamic therapy(PDT) on the expressions of MMP-9, MMP-13 and TIMP-1 of hypertrophic scar model in rabbit ears, and analyze the possible therapeutic mechanisms of ALA-PDT treatment to hypertrophic scars of rabbit ears. Methods: The experimental animals were randomly divided into normal control, negative control, high concentration of ALA-PDT, low concentration of ALA-PDT and PDT groups. The latter three groups received ALA-PDT treatment or PDT treatment once a week for 3 weeks. The specimens of the rabbits were collected respectively 1, 2 and 3 months after treatment to be used for RT-PCR and Western-blot test. Results: 1, 2 and 3 months after PDT treatment, the expressions of MMP-9 and MMP-13(including mRNA and protein) in hypertrophic scar tissues of three treatment groups were significantly higher than those of the negative control group(P<0.01), and the expression of TIMP-1 mRNA and protein of three treatment groups were significantly lower than that of the negative control group(P<0.01). There were also significant differences between high-concentration ALA-PDT treatment group and the low one(P<0.05). Conclusion: ALA-PDT is effective in treating hypertrophic scars of rabbit ears, and its possible therapeutic mechanisms are that ALA-PDT treatment generates oxidation activation effect to activate the activity of MMPs and induces the photoaging of fibroblasts of hypertrophic scar tissues of rabbit ears to inhibit the activity of TIMPs, which causes the up-regulation of MMPs and the down-regulation of TIMPs. Because of this, the degradation of collagen and ECM is accelerated and the formation of scars is suppressed.
基金the National Natural Science Foundation of China(grant no.81872219)Science and Technology Project of Hunan Provincial Health Commission(grant no.B2015-040)+2 种基金Major Scientific and Technological Projects in Hunan Province(grant no.2019SK1010)2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant(grant nos.2020LKSFG18B,2020LKSFG02E)Guangdong University Innovation Team Project(grant no.2021KCXTD047).
文摘Background:The role of autophagy in the formation of hypertrophic scars(HS)remains unclear.This study aimed to explore the role and potential mechanism of autophagy during the development of HS.Methods:RNA and protein expression levels of Beclin-1,p62,and LC3II in normal skin tissues and HS specimens from different patients were examined.Autophagy inducers and inhibitors were used to cure established HS in rabbit ears,and the expression of Beclin-1,p62,and LC3II at the RNA and protein level was determined.Lastly,the effects of autophagy inducers and inhibitors on HS development were analyzed.Results:Compared to normal skin tissues,the expression of LC3II and Beclin-1 was higher(P<0.05),while that of p62 was lower(P<0.05)in HS tissues.In addition,the LC3II/LC3I ratio was increased during HS formation,and the altered expression of the three proteins stabilized after one year.Administration of autophagy inducers enhanced the formation of HS as well as the expression levels of LC3II and Beclin-1 but decreased p62 expression.Meanwhile,administration of autophagy inhibitors increased the expression of LC3II,Beclin-1,and p62,along with reduced HS formation.Conclusion:Autophagic activity increased during HS initiation and subsequent stabilization.In addition,autophagy inhibitors were able to inhibit HS formation by suppressing autophagy,whereas autophagy inducers promoted scar hyperplasia by enhancing autophagy。
文摘目的:他克莫司是临床广泛应用的一种药物,其对增生性瘢痕是否产生作用并无相关报道,为此提出并证实了他克莫司可以抑制兔耳瘢痕增生。方法:建立兔耳增生性瘢痕模型,选10只新西兰大耳白兔双耳腹侧用打孔器制作直径1cm圆形创面,伤后14天创面上皮化后给药,每只兔左耳为空白对照组涂等剂量凡士林软膏,右耳为他克莫司治疗组。分别在伤后14天、21天2、8天3、5天和49天采集标本,行HE染色,观察形态学差异;Real-t i me PCR检测纤维化相关因子TGF-β1、TGF-β2、Col l agen-α1等的表达。结果:HE染色可见他克莫司组成纤维细胞数量及胶原纤维较对照组明显减少,PCR结果可见TGF-β1、TGF-β2及Col l agen-α1表达较对照组在各时间点均减少。结论:实验组较对照组瘢痕明显减轻,证明他克莫司显著抑制兔耳瘢痕增生,可作为临床上治疗及预防瘢痕增生的全新疗法。
文摘目的研究二氢青蒿素对兔耳增生性瘢痕增生的影响。方法选取20只成年新西兰大耳白兔建立兔耳增生性瘢痕动物模型,待伤口上皮化后,将其随机分成两组,每组10只。对照组灌胃给予10 m L的生理盐水,实验组灌胃给予10 m L的二氢青蒿素,1次/天,连续给予1周。记录观察术后20 d和50 d 2组兔耳瘢痕的发生和兔耳瘢痕的大小。结果对照组兔耳瘢痕的发生率大于实验组兔耳瘢痕的发生率,差异有统计学意义(P<0.05),表明二氢青蒿素具有降低兔耳瘢痕发生的疗效;对照组兔耳瘢痕大于实验组兔耳瘢痕,差异有统计学意义(P<0.050),表明二氢青蒿素具有治疗兔耳瘢痕的作用。结论二氢青蒿素对兔耳增生性瘢痕具有显著的疗效,作为一种有效的药物,值得对其做进一步的研究。