Hypertrophic Scar In Rabbit Ears Research Articles

The role of Th1/Th2 cell chemokine expression in hypertrophic scar.

The aim of this study was to study the role of Th1/Th2 cell-associated chemokines in the formation of hypertrophic scars in rabbit ears. Twenty-six New Zealand white rabbits were used to establish the hypertrophic scar model of rabbit ear and the normal scar model of rabbit's back. Two rabbits were sacrificed on days 0 and 21, 28, 35, 42, 49, 56, and 63 after operation. The specimens were stained with haematoxylin-eosin (HE). Scar elevation index (SEI) was used to detect the expression of 10 chemokines related to Th1/Th2 cells in both scar formation expressions. Real-time polymerase chain reaction (PCR) results showed that two chemokines (CXCL10, CXCL12) were highly expressed during the formation of normal scar, and there was almost no expression during the formation of hypertrophic scar (*P < 0.05). The chemokines (CCL2, CCL3, CCL4, CCL5, CCL7, CCL13, CX3CL1) were almost non-expressed in the formation of normal scars but were expressed for a long time in the formation of hypertrophic scars. The four chemokines, CCL2, CCL4, CCL5, and CX3CL1, maintained a long-term high expression level during the formation of hypertrophic scars (P < 0.01). There were also three chemokines (CCL14, CCL19, CCL21) that were almost undetectable in normal scarring, but there was transiently low-level expression (P < 0.05) only during the peak proliferative phase in proliferative scarring. Th1/Th2 cell-associated chemokines are different in the type, quantity and expression, and maintenance time of rabbit ear hypertrophic scars.

Study on physicochemical properties of paeonol-Helix aspersa muller nanogel and its inhibitory effects on hypertrophic scar tissue in rabbit ear

To prepare Helix aspersa muller-paeonol nanogel( PAE-HAM-Gels) with anti-proliferative scar effect,evaluate its skin penetration,retention and irritation,and to investigate its prevention and treatment effect for hypertrophic scar in rabbit ears. The dermal retention,transdermal rate and cumulative permeability of paeonol were investigated in vitro by using the modified Franz diffusion cell and the abdominal skin of suckling pigs,SD rats and KM mice,respectively,and the in vitro permeation curves were drawn. The normal skin of the back of New Zealand rabbits was continuously treated with PAE-HAM-Gels for 7 days,and the physiological state of the skin was observed under light microscope after HE staining by using homologous left and right contrast method. The hypertrophic scar model in rabbit ears was established,and the New Zealand rabbits were randomly divided into blank group,model group,positive drug group,PAE-Gels group and PAE-HAM-Gels group. After 28 days of administration,the scar hyperplasia rate and scar elevation index( SEI) of each group were calculated; the scar tissues were taken and stained with Masson for observation of collagen fibers and muscle fibers hyperplasia under light microscope,and the expression level of TGF-β1 in each group was detected. The Qnof PAE-HAM-Gels in aqueous solution was in line with the Higuchi equation,and its transdermal rate,cumulative permeation and dermal retention in different animal skins were all higher than those of PAE-Gels. The skin of the drug-administered group was intact,without erythema,edema or other phenomena; under light microscope,the subcutaneous tissue and the epidermal cells were neatly arranged with uniform thickness,which showed no difference from the blank group. The scar hyperplasia rate of the PAE-HAM-Gels group was 62. 50%; SEI was 2. 17±0. 33 and TGF-β1 was( 815. 4±34. 69) ng·L~(-1),significantly different from those in model group( P<0. 01). Masson staining showed that as compared with the model group,the number of collagen fibers and muscle fibers was small and the arrangement was loose and tidy in the PAE-HAM-Gels group,with regular arrangement of chondrocytes and a small number of inflammatory cells and microvessels.PAE-HAM-Gels have good transdermal properties and dermal retention without skin irritation,offering a promising therapeutic strategy for transdermal delivery during the prevention and treatment of hypertrophic scar in rabbit ears.

Early intervention of fractional carbon dioxide laser on fresh traumatic scar

To determine the combined therapeutic effect of fractional carbon dioxide laser and silicone gel on fresh traumatic scars using a rabbit ear hypertrophic scar (EHS) model, as well as on human subjects. The rabbit EHS model was established by punching four circular wounds in each ear and respectively treated with carbon dioxide laser, silicone gel, and the combination of both, while one wound was left untreated. In addition, a validation group of five rabbits was also included wherein the wounds were treated with triamcinolone, IFN-α, and normal saline, with one untreated control. The gross hyperplasic changes and the histological features were analyzed, and the scar elevation index (SEI) was calculated for each treatment group. In the rabbit model, the untreated control wounds showed hypertrophic growth, whereas triamcinolone or IFN-α showed an inhibitory effect, similar to that on hypertrophic scars in humans, thereby proving the feasibility of our animal model. The SEI peaked 2 months after treatment and was respectively 2.28 ± 0.56, 1.85 ± 0.33, 1.91 ± 0.34, and 1.45 ± 0.22 in the untreated control, and the silicone, laser, and combined treatment groups, clearly indicating a significant therapeutic effect of the combined treatment modality (p < 0.01). The fibroblast and microvascular counts also showed similar trends in each group. Early application of fractional carbon dioxide laser can prevent hypertrophic scars; the combined use of laser and silicone gel was more effective with less recovery time, thereby worthy of clinical promotion.

Effects of melatonin on the expression of type I collagen and type III collagen in hypertrophic scar of rabbit ear

Objective To observe the effect of melatonin on the expression of type Ⅰ collagen and type Ⅲ collagen in hypertrophic scar of rabbit ears. Methods The animal model of hypertrophic scar of rabbit ears was established, and the experimental group of melatonin and the blank control group were set up. Experimental group: intraperitoneal injection of 5.0 mg/kg melatonin every day; blank control group: intraperitoneal injection of equal amount of saline daily. After 6 weeks of rearing, cicatricial tissue and fixed specimen were collected. The thickness of the scar was measured by hematoxylin-eosin (HE) staining and the percentage of the area of collagen was measured by Sirius red staining. Results On the forty-second day, the degree of scar hyperplasia in the experimental group was significantly lower than that in the control group. The thickness of scar tissue in the experimental group was (920.30±227.56) μm, and the thickness of the control group was (1 033.10±263.59) μm. The scar hyperplasia in the control group was stronger than that in the experimental group (P=0.000). The content of type Ⅰ collagen in experimental group was (0.115±0.051)%, and the content of type Ⅰ collagen in control group was (0.148±0.043)%, the content of type Ⅰ collagen in the experimental group was lower than that of the control group (P=0.026). The content of type Ⅲ collagen in experimental group was (0.145±0.041)%, while that in control group was (0.121±0.034)%, the content of type Ⅲ collagen in the experimental group was higher than that of the control group (P=0.013). Conclusion The results indicate that melatonin can reduce scar proliferation through regulating the proportion of collagen type Ⅰ and type Ⅲ. Key words: Melatonin; Hypertrophic scar; Collagen

Effects of low concentration 5-fluorouracil and triamcinolone acetonide on ear hypertrophic scar in a rat model

Objective To explore the effect of low concentration 5-fluorouracil combined with triamcinolone acetonide on rabbit ear hypertrophic scar model. Methods White rabbits post-traumatic scars were randomly divided into A , B , C and D groups, each group contained 18 cases. Group A was given triamcinolone acetonide and low concentration 5-fluorouracil, Group B was given low concentration 5 - fluorouracil, Group C was given triamcinolone acetonide and Group D was used as the control group. The dynamic changes of the scar were observed by naked eyes, hematoxylin-eosin (HE) staining and van Gieson (VG) staining through microscope. Vascular endothelial growth factor (VEGF) and CD34 were detected and compared within 4 groups by immunohistochemical staining. Results We successfully established a rabbit ear scar model. It was observed that the scars of Groups A, B and C had been shorter and flatter than Group D, close to the normal tissue. In HE and VG staining, the number of fibroblasts, inflammatory cells, blood vessels in groups A, B and C had been decreased, compared with Group D. Immunohistochemical results showed that the positive rates of VEGF and CD34 from the most to the lest were Groups D, B, C and A. The scar proliferation index from the most to the lest were Groups D, B, C and A. Conclusions The effect of low concentration 5-fluorouracil in treatment of the rabbit ear hypertrophic scar is better than that of triamcinolone acetonide. Low concentration 5-fluorouracil combined with triamcinolone acetonide has a synergistic effect in treatment of hypertrophic scar, which has better effect than that of low concentration 5-fluorouracil or triamcinolone acetonide alone. Key words: Hypertrophic scar; 5-fluorouracil; Triamcinolone acetonide; Vascular endothelial growth factor; CD34

Effect of hyperbaric oxygen on the process of hypertrophic scar formation in rabbit ears.

To explore the influence of hyperbaric oxygen on scar formation in rabbit ears. A total of 20 New Zealand rabbits were selected to establish the hypertrophic scar model on the ears. The rabbits were randomly divided into control group and experimental group (7d, 14d, 21d, and 28d group according to different HBO treatment days),each experimental group received hyperbaric oxygen treatment after the operation at the same time everyday for 1hour. After the day 29, the scars were collected. Histomorphological change in scars was observed by hematoxylin-eosin staining, Masson staining, and transmission electrical microscope. The expression of bax, bcl-2, and the cell apoptosis rate was detected by immunohistochemical method. (i) Both number of fibroblast and amount of collagen fibrils in experimental group were significantly reduced compared with those in control group. In Masson staining, arrangement of collagen fibrils in experimental group was much more irregular and coarse than control groups. (ii) HI value can be found much smaller in the experimental groups than the control (P<.05). Among the four experimental groups, there is significant difference among 7d, 14d, and 21d groups (P<.05), while there is no difference between 21d and 28d groups (P>.05). (iii) Expression of Bax could be detected up-regulated in experimental group (P<.05). While the expression of Bcl-2 is detected significantly down-regulated in experimental group than that in control group (P<.05). Compared with the 7d group, the expression of Bax and Bcl-2 has significant difference in 14d group (P<.05), and the expression of this two factors in 21d group has significant difference comparing with 14d group(P<.05),but there is no significant difference between 28d group and 21d group(P>.05). (iv) Significant difference of cell apoptosis rate can be detected between the experimental groups and the control group (P<.05). Among the four experimental groups, there is significant difference among 7d, 14d, and 21d groups (P<.05), while there is no difference between 21d and 28d groups (P>.05). The hyperbaric oxygen can up-regulate bax/bcl-2 value, increase the cell apoptosis rate, and inhibit the early hypertrophic scar in rabbit ears.

Experimental Study of 5-fluorouracil Encapsulated Ethosomes Combined with CO2 Fractional Laser to Treat Hypertrophic Scar

ObjectiveThis study is designed to explore permeability of ethosomes encapsulated with 5-florouracil (5-FU) mediated by CO2 fractional laser on hypertrophic scar tissues. Moreover, therapeutic and duration effect of CO2 fractional laser combined with 5-FU encapsulated ethosomes in rabbit ear hypertrophic scar model will be evaluated.MethodsThe permeated amount of 5-FU and retention contents of 5-FU were both determined by high-performance liquid chromatography (HPLC). Fluorescence intensities of ethosomes encapsulated with 5-FU (5E) labeled with Rodanmin 6GO (Rho) were measured by confocal laser scanning microscopy (CLSM). The permeability promotion of 5E labeled with Rho in rabbit ear hypertrophic scar mediated by CO2 fractional laser was evaluated at 0 h, 6 h, 12 h, 24 h, 3 days and 7 days after the irradiation. The opening rates of the micro-channels were calculated according to CLSM. The therapeutic effect of 5EL was evaluated on rabbit ear hypertrophic scar in vivo. Relative thickness of rabbit ear hypertrophic scar before and after the treatment was measured by caliper method. Scar elevation index (SEI) of rabbit ear hypertrophic scar was measured using H&E staining.ResultsThe data showed that the penetration amount of 5EL group was higher than 5E group (4.15 ± 2.22 vs. 0.73 ± 0.33; p < 0.05) after 1-h treatment. Additionally, the penetration amount of 5EL was higher than that of the 5E group (107.61 ± 13.27 vs. 20.73 ± 3.77; p < 0.05) after 24-h treatment. The retention contents of the 5EL group also showed higher level than 5E group (24.42 ± 4.37 vs.12.25 ± 1.64; p < 0.05). The fluorescence intensity of Rho in hypertrophic scar tissues of the 5EL group was higher than that of the 5E group at different time points (1, 6, and 24 h). The opening rates of the micro-channels were decreased gradually within 24 h, and micro-channels were closed completely 3 days after the irradiation by CO2 fractional laser. The relative thickness and SEI of rabbit ear hypertrophic scar after 7 days of treatment in the 5EL group were significantly lower than the 5E group.ConclusionCO2 fractional laser combined with topical 5E can be effective in the treatment of hypertrophic scar in vivo and supply a novel therapy method for human hypertrophic scar.

Recombinant human endostatin reduces hypertrophic scar formation in rabbit ear model through down-regulation of VEGF and TIMP-1.

Recombinant human endostatin (Endostar) has been widely used to suppress angiogenesis in carcinoma patients. Hypertrophic scar (HS) tissue, much like a carcinoma, is often associated with angiogenesis. However, there have been few studies conducted on the effects of Endostar on HS or its mechanism. This paper investigated the effects Endostar on the HS of rabbit ears and studied the effects of Endostar on VEGF and TIMP-1 expression. Sixteen New Zealand white rabbits were used to establish HS models. Then, rabbit ears containing HS were randomly assigned to either the Endostar group or the control group. The changes of appearance and histology were evaluated using the naked eye, hematoxylin eosin staining, and a scar elevation index. The VEGF and TIMP-1 expressions were detected by immunohistochemical staining, RT-PCR, and western blot. The thickness of the connective tissue in the Endostar group were thinner, the numbers of micro vessels and fibroblasts were fewer, and the collagen fibers were smoother. Moreover, the mRNA and protein expressions of VEGF and TIMP-1 in the Endostar group were significantly lower than those in the control group. The results suggested that Endostar reduced the formation of HS by down-regulation of VEGF and TIMP-1 expressions.

Enhanced in vivo delivery of 5-fluorouracil by ethosomal gels in rabbit ear hypertrophic scar model.

Applying Ethosomal Gels (EGs) in transdermal drug delivery systems has evoked considerable interest because of their good water-solubility and biocompatibility. However, there has not been an explicit description of applying EGs as a vehicle for hypertrophic scars treatment. Here, a novel transdermal EGs loaded with 5-fluorouracil (5-FU EGs) was successfully prepared and characterized. The stability assay in vitro revealed that 5-FU EGs stored for a period of 30 days at 4 ± 1 °C had a better size stability than that at 25 ± 1 °C. Furthermore, using confocal laser scanning microscopy, EGs labeled with Rhodamine 6 G penetrated into the deep dermis of the hypertrophic scar within 24 h in the rabbit ear hypertrophic model suggested that the EGs were an optional delivery carrier through scar tissues. In addition, the value of the Scar Elevation Index (SEI) of 5-FU EGs group in the rabbit ear scar model was lower than that of 5-FU Phosphate Buffered Saline gel and Control groups. To conclude, these results suggest that EGs delivery system loaded 5-fluorouracil is a perfect candidate drug for hypertrophic scars therapy in future.

Photodynamic therapy inhibits the formation of hypertrophic scars in rabbit ears by regulating metalloproteinases and tissue inhibitor of metalloproteinase-1

Hypertrophic scarring (HS) is a chronic skin condition, and inhibition of normal fibroblast ageing plays an important role in its pathogenesis. Photodynamic therapy (PDT) is known to inhibit synthesis of collagen proliferation in blood vessels and fibroblasts in scar tissue, with no significant adverse reactions reported. To investigate the effect of PDT in the rabbit ear model of HS, and the specific mechanism of action of PDT. We assessed the clinical and histopathological appearance of rabbit ears with HS with and without PDT. In addition, mRNA levels of matrix metalloproteinase (MMP)-2, MMP-3, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1, and concentration of β-galactose were all measured to confirm cell senescence. Our data indicate that PDT can accelerate fibroblast ageing by increasing the ratio of MMPs to TIMP, in addition to promoting degradation of collagen and extracellular matrix, thereby inhibiting HS formation. These effects lasted for up to 60days, and induced no significant adverse local or systemic reactions. The efficacy of the treatment can be maximized by applying an appropriately high concentration of aminolaevulinic acid. PDT can induce senescence in fibroblasts, and may constitute a useful treatment for pathological scarring.

Effect of tetrandine on gene expression of collagen type I, collagen type III and TGF-beta1 in scar tissue's of rabbits ear

To observe the effect of tetrandine on gene expression of collagen type I, collagen type III, transformation growth factor-beta1 and to investigate the inhibitory effect of tetrandine on the scar tissue hyperplasia in rabbits' ears. After the scar model was formed on the rabbits' ears, the rabbits were divided into 4 groups to receive intro-lesion injection with saline, or prednisolone (Pre) or tetrandrine in low concentration (L-Tet, 1.0 mg/ml) or tetrandrine in high concentration (H-Tet, 7.5 mg/ml). The morphological changes of scar tissue were observed. The changes of fibroblasts quantity and collagen expression were observed with HE and Masson staining. Immunohistochemical study was used to observe the expression level of collagen type I and collagen type III and TGF-beta1. Collagen type I and collagen type III and TGF-beta1, and signal factor Smad 3 mRNA were detected with RT-PCR. (1) 24 days after injury, all the wounds healed completely with formation of red, tough and hypertrophic scar. HE and Masson staining showed significant increase of fibroblasts and collagen density with irregularly arrangement. (2) Compared with that in saline group, the scar in other groups became softer, lighter and thinner, especially in H-Tet group. (3) HE and Masson staining shows the scar in Tet and Pre groups contained less fibroblasts and lower collagen dentsity with comparatively regular arrangement than that in saline group (P < 0.01), especially in H-Tet group. (4) According to the immunohistochemical study, the expression of collage type I and III and TGF-beta was positive in all the groups, but the positive rate and the ratio of collagen density I to III decreased in the order of saline, L-Tet, H-Tet and Pre groups (P < 0.01). (5) PT-PCR detection results showed that the amplification bands brightness of collagen type I and III and TGF-beta1 and signal molecular Smad 3 mRNA in scar tissue were obviously different. Compared with that in saline group, the expression of collagen type I and III and TGF-beta1 and Smad 3 mRNA decreased in Tet and Pre groups (P < 0.01). H-Tet group showed the most obvious reduce in the expression of type I collagen and TGF-beta1 and Smad 3 mRNA. Conclusions Tetrandine can significantly suppress the expression of collagen type I and collagen type III and TGF-beta1 on hypertrophic scar of rabbit ears, and reduce signal factor Smad 3 mRNA' s expression. It may be one of the important mechanism for its inhibitory effect on scar hyperplasia.

Endostar Injection Inhibits Rabbit Ear Hypertrophic Scar Formation

This study aims to investigate the effect of Endostar injection on the rabbit ear hypertrophic scar formation and expand the use of Endostar. The rabbit ear hypertrophic scar models were established 4 weeks postoperation and were treated with Endostar injection; the control group was injected with saline, once a week, 3 times totally. At the seventh week, the scar tissue was harvested and processed with hematoxylin and eosin (HE) staining and CD34 immunohistochemistry and cell apoptosis assay. In addition, the endothelial cell was cultured and seeded on Martrigel with different concentrations of Endostar to observe the vessel tube formation. The results showed that the volume of the hypertrophic scar with Endostar injection was greatly reduced compared with what was seen in the control group; meanwhile, HE staining showed that the cell number decreased and collagen density became looser. In addition, the CD34 staining indicated that microvessel formation in the study group also decreased and cell apoptosis increased. In vitro, the addition of Endostar could reduce vessel tube formation in a dose-dependent manner. In conclusion, the Endostar is effective for hypertrophic scar inhibition and could be a potential tool to treat scars.

Antisense CTGF inhibits the expression of CTGF in hypertrophic scar of rabbit ears

Objective To investigate a medicine which can inhibit the expression of connective tissue growth factor (CTGF) in hypertrophic scar of rabbit ears. Methods 24 bigears white rabbits were used to establish a model of hypertrophic scar of rabbit ears, which was randomly divided into four groups. The hypertrophic scar was injected intralesionally with antisense CTGF (group A), betamethason (group B), triamcinolone acetonide (group C) and physiological saline (group D). Some scar tissue samples were sectioned in every group when the scar was treated after 7, 14, 30, and 60 days, respectively. The expression of CTGF mRNA in the scar was assessed by in situ hybridization and hematoxylin and eosin stain (HE stain) in every samples. Results The expression of CTGF mRNA and the counting of fibroblasts decreased in group A, which showed statistical difference as compared with groups B, C and D. Conclusions The results suggesz that antisense CTGF is able to inhibit the proliferation process of hypertrophic scar in rabbit ears and to remarkably decrease the degree of fiborsis in the scar. Key words: Antisense connective tissue growth factor; Connective tissue growth factor; Rabbit ear; Hyertrophic scar; Image analysis

Inhibitory effect of small proteoglycan, decorin, on hypertrophic scars in rabbit ears

Objective To observe the inhibitory effect of decorin on hypertrophic scar in rabbit ears. Methods Full-thickness excisional wounds, 8 mm in diameter, were made over the ventral side of ears in 8 adult New Zealand white rabbits, and 48 hypertrophic scars in total. Then the rabbits were divided into two groups: group A, experimental group (decorin, 10 mg/L); group B, control group (physiological saline). At the 20th and 30th day after operation, the hypertrophic scars were injected with decorin (group A) and saline (group B) intralesionally. Samples were harvested 20 days after the last injection (50th day) for measurement of scar elevation index (SEI). The expression of type Ⅰ collagen protein and type Ⅰ pro-collagen mRNA was assessed by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) respectively. Results Compared with group B, the scars appeared to be flatter,softer, and lighter in color in group A. The SEI in group A and group B was 2. 8970 ±0. 2066 and 3. 5210 ±0. 1960 respectively. The expression of type Ⅰ collagen protein and type Ⅰ pro-collagen mRNA in group A was 0. 221 20 ±0. 027 06 and 0. 372 50 ±0.026 78 respectively, and that in group B was 0. 336 90 ±0.030 74 and 0.645 60 ±0.029 94 respectively ( all P ＜ 0.05). Conclusion Decorin can inhibit the proliferation process of hypertrophic scar in rabbit ears and remarkably decrease the degree of fibrosis in the scar. Key words: Hypertrophic scar; Proteoglycan

Effects of carboxyl methylchitosan on hypertrophic scars in rabbit ears

：Objective To investigatethe effect of carboxyl methyl chitosan on hypertrophic scars by establishing ahypertrophic scar model on the ventral side of rabbit ears.Methods Full-thick-nessexcisional wounds,1 cm in diameter,were made in the ears of 12 adult New Zealand whiterabbits,and 123 hypertrophic sears were made in all.Then the rabbits were divided into 3groups:group A was an experimental group (carboxyl methyl chitosan,500μg/ml),group B was a control group1 (triamcinolone),and group C was control group 2 (physiological saline).All the scarswere injected with drugs on the 30th and 40th days after operation,and then the sampleswere collected on the 35th and 45th day and analyzed.Results Compared with group C,group Aappeared to be flatter,softer,and lighter in color;the area density of fibroblastdecreased using HE stain and masson stain (P 0.05).Conclusion Injectionof carboxyl methyl chitosan into Iocal hypertrophic scars On rabbit ears has similareffects to triamcinolone,and both of them can prevent and cure hypertrophic scars inproliferative stage. Key words: Hypertrophic scars; Carboxyl methyl Chitosan; Animal model

Effects of 15-deoxy-△12,14-prostagliandxin J2 on the expression of type I collagen in hypertrophic scar of rabbit ears

Objective To investigate the effect of 15d-PGJ2 on the expression of type Ⅰ collagen in hypertrophic scar of rabbit ears, and the possibility of hypertrophic scar treated by 15d-PGJ2. Methods Eighteen New Zealand white rabbits were used to establish the hypertrophic scar models on the rabbit ears. The wounds were created as follows: 2 cm × 3 cm wounds with total skin loses on the ventral side, 2wounds for each ear, total 72 wounds. The wounds were randomly divided into the 15d-PGJ2 treatment group and NS control group. A total of 20 μl 15d-PGJ2 or NS was injected into the ear scar once a day for 7 days. At the 14th and 21st day after the injection, 18 scars in each group were harvested. The expression levels of type Ⅰ collagen was detected by immunohistochemistry, fluorescence quantitative polymerase chain reaction (PCR) and Western blotting. Results Compared with the NS control group, the 15d-PGJ2-treated scars appeared to be smaller, softer, flatter and lighter in color. The expression of type Ⅰcollagen was mainly distributed in matrix, fibroblast cytoplasma and the vascular wall. The mRNA and protein levels of type Ⅰ collagen were significantly decreased in the 15d-PGJ2-treated group as compared with those in the NS control group at different time points (P < 0. 05). Conclusion 15d-PGJ2, the ligand of PPAR-γ, can reduce the expression of type Ⅰ collagen in hypertrophic scar of rabbit ears and plays an important role in the prevention and treatment of hypertrophic scar. It offers a new way for treating the hypertrophic scar clinically. Key words: Hypertrophic scar; PPAR-γ; Collagen

Effect of 15-deoxy-△~(12,14)-prostagliandxin J2 on hypertrophic scar in rabbit ear

Objective To investigate the effect of 15d-PGJ2 on the expression of collagen type,CTGF and a-SMA in the hypertrophic scar in the rabbit ear,and the possibility of hypertrophic scar treated by 15d-PGJ2.Methods 18 New Zealand white rabbits were used to establish a hypertrophic scar model on the rabbit ear.The wounds were established as follows:2 cm × 3 cm wounds with total skin loses on the ventral side,2 wounds for each ear,totally 72 wounds.The wounds were randomly divided into the 15d-PGJ2 treatment group and NS control group.20μl 15d-PGJ2 or NS was injected into the ear scar once a day for 7 days.At 7,14 and 21 days after the injection,12 scars of each group were harvested.The expression of collagen type Ⅰ,CTGF and a-SMA was detected by immunohistochemical method.Results Excessive dermal scars on rabbit ears that were similar to human hypertrophic scar appeared in the two groups.Compared with the NS-treated scars group,the 15d-PGJ2-treated scars appeared to be smaller,softer,flatter and lighter in color.The expression of collagen type Ⅰ,CTGF and a-SMA in the 15d-PGJ2 group was significantly decreased as compared with that in the control group at different time points(P＜0.05).Conclusion 15d-PGJ2,the ligand of PPAR-r,can reduce the expression of collagen type Ⅰ,CTGF and a-SMA of hypertrophic scar in the rabbit ears and plays an important role in the prevention and treatment of hypertrophic scar.It may provide a new approach for the treatment of hypertrophic scar in clinical setting. Key words: Hypertrophic scar; Peroxisome proliferator activated receptor-r; PPAR-r; Collagen type Ⅰ; Connective tissue growth factor; CTGF; a-Smooth muscle actin; a-SMA

Artemisinin and artesunate cream in the prevention and treatment of hypertrophic Scar in rabbit ears

Objective To evaluate the preventive and therapeutic effects of artemisinin and artesunate on hypertrophic scar in rabbit ears.Methods Full-thickness wounds to cartilage were created in New Zealand white rabbit cars to establish animal models of hypertrophic scar.Cream was prepared with artemisinin or artesunate.A total of 96 hypertrophic scars were divided into 4 groups to receive the treatment with artemisinin cream.artesunate cream.cream vehicle(vehicle control)or no treatment(blank control)28 days after wounds were created.After 28-day treatment,animals were scarified,scars were incised and examined with HE-staining and VG-staining.Hypertrophy index.numerical density of fibroblasts and area density of collagen fibers were calculated.Results Compared with vehicle and blank controls,the scars were softer and flatter,the volume of fibroblasts decreased,and collagen fibers appeared to be more regulated and sparse in artemisiIlin or artesunate cream-treated groups.The Hypertrophy index.numerical density of fibroblasts.area density of collagen fibers were(1.452±0.27),(3638.245±463.0)cells/mm2,(32.29±6.9)%in artemisinin cream-treated group,respectively,(1.445±0.24),(3585.016±638.9)cells/mm2,(34.74±8.27)%in artesunate cream-treated group,respectively.All the three parameters were significantly reduced in artemisinin and artesunate groups than in blank and vehicle control groups(all P＜0.0 1).but no significant difference was found between artemisinin and artesunate groups (P＞0.05).Conclusion Artemisinin and artestmate cream has a reliable efficacy in the prevention and treatment of hypertrophic scar in animal models. Key words: Artemisinin; Artesunate; Cicatrix; Models,animal

Antisense CTGF inhibits hypertrophic scar of rabbit ears

目的 探讨反义结缔组织生长因子(connective tissue grouth factro,CTGF)对兔耳增生性瘢痕的抑制作用.方法 选择20只大耳白兔建立增生性瘢痕动物模型,随机分成5组,对照组为A组,注射转化生长因子β1(TGF-β1)为B组,注射CTGF为C组,先后注射TGF-β1和CTGF为D组,注射反义CTGF为E组,每个治疗组又分为治疗7、14、20 d 3组;通过逆转录-聚合酶链式反应(RT-PCR)方法检测增生性瘢痕中CTGF mRNA的表达,免疫组织化学检测CTGF蛋白表达,HE、Masson染色观察切片内成纤维细胞数密度,计算机辅助图像分析测算切片内胶原纤维面密度.结果 E组中CTGF mRNA、蛋白表达、成纤维细胞数密度和胶原纤维面密度均降低,与A、B组比较,差异有统计学意义(P＜0.05).结论 反义CTGF可以抑制兔耳增生性瘢痕的增殖过程,使瘢痕组织纤维化程度明显减轻。

Effects of pentifylline on hypertrophic scars in rabbit ears

目的 观察己基可可碱对兔耳增生性瘢痕组织的影响.方法建立兔耳增生性瘢痕动物模型,21 d后瘢痕局部注射不同浓度的己基可可碱或生理盐水,49 d后观察药物对瘢痕增生指数(hypertrophic index,HI)的影响及采用图像系统分析瘢痕组织中成纤维细胞数量和胶原含量的变化.结果治疗组中HI与药物浓度呈负相关(P＜0.05),治疗组瘢痕组织中成纤维细胞数量与胶原含量均明显减少,呈剂量效应关系;与生理盐水对照组比较,差异有统计学意义(P＜0.01).结论己基可可碱能抑制瘢痕组织中成纤维细胞增殖,并使胶原合成减少,从而抑制兔耳增生性瘢痕组织增生,有望成为防治增生性瘢痕的新药物。