关键词: 瘢痕, 增生性瘢痕, 己酮可可碱, 疾病模型, 动物, 大鼠, Sprague-Dawley, 成纤维细胞

Abstract: 【Abstract】 Objective To investigate the effects of pentoxifylline and allantoin-based moisturizer on fibroblast proliferation and inflammatory factor expression in a Sprague-Dawley rat model of hypertrophic scars. Methods A hypertrophic scar model was established in Sprague-Dawley rats using the scalding method. Rats were randomly divided into a moisturizing group and a non-moisturizing group according to whether allantoin cream was applied, and each group was further divided into 4 subgroups based on injected medications: experimental group （intradermally injected with 2.0 mg/ml pentoxifylline solution）, positive control group （intradermally injected with an equal volume of 8.0 mg/ml triamcinolone acetonide injection）, negative control group （intradermally injected with an equal volume of sterile distilled water）, and blank control group （without intervention）. Scar severity was evaluated using the Vancouver Scar Scale （VSS） before drug administration and at 2, 4, and 6 weeks after administration; skin tissues were collected for routine hematoxylin-eosin staining and fibroblast counting. At 6 weeks after administration, the rats were sacrificed, and the expression of cyclooxygenase-2 （COX-2）, interleukin-6 （IL-6）, and tumor necrosis factor-α （TNF-α） in scar tissues was determined by Western blot analysis. Differences among groups were analyzed using repeated measures analysis of variance or two-way analysis of variance, and multiple comparisons were performed using the Bonferroni correction. P < 0.05 was considered statistically significant. Results After scald modeling, histopathological examination of the rat skin lesions revealed marked proliferation of enlarged fibroblasts, abundant thick, dense, and disorganized collagen fibers, and capillary proliferation. From 2 to 6 weeks after modeling, no significant differences in VSS scores were observed among the groups （Finteraction = 1.71, Ftime = 0.21, Fintervention = 2.04, all P > 0.05）, while significant differences in fibroblast counts were observed among the groups （Ftime = 9 647.00, Fgroup = 630.20, Finteraction = 11.34, all P < 0.001）. Specifically, at 2 weeks after the start of treatment, in the moisturizing group, the fibroblast count was significantly lower in the experimental group （110.00 ± 6.02） than in the positive control group, negative control group, and blank control group （125.49 ± 2.36, 157.65 ± 6.67, 158.32 ± 4.20, respectively; all P < 0.05）; in the non-moisturizing group, the fibroblast count in the experimental group did not differ significantly from that in the positive control group （134.2 ± 24.94 vs. 139.46 ± 5.91, P > 0.05）, but was significantly lower than those in the negative control group and blank control group （all P < 0.05）; at 4 and 6 weeks, in both the moisturizing group and non-moisturizing group, the fibroblast counts in the experimental group were significantly lower than those in the positive control group, negative control group, and blank control group （all P < 0.05）; at 2, 4, and 6 weeks, the fibroblast counts in the experimental group were significantly lower in the moisturizing group than in the non-moisturizing group （all P < 0.05）. At 6 weeks, the expression of COX-2 and TNF-α did not differ significantly among the groups （all P > 0.05）; in the moisturizing group, the IL-6 expression level was 0.95 ± 0.06, 0.88 ± 0.16, 0.64 ± 0.21, and 0.38 ± 0.07 in the experimental group, positive control group, negative control group, and blank control group, respectively; in the non-moisturizing group, the IL-6 expression level was 0.33 ± 0.06, 0.81 ± 0.18, 0.66 ± 0.15, and 0.94 ± 0.010 in the above four groups, respectively; neither pentoxifylline （Fdrug = 1.10, P > 0.05） nor moisturization （Fmoisturization = 0.10, P > 0.05） showed a significant main effect on IL-6 expression; however, their interaction effect was significant （Finteraction = 6.54, P < 0.001）; in the non-moisturizing group, the IL-6 expression level was significantly lower in the experimental group than in the blank control group （t = 3.22, P < 0.05）; however, the IL-6 expression level in the blank control group was significantly lower in the moisturizing group than in the non-moisturizing group （t = 2.96, P < 0.01）. Conclusion Local injection of pentoxifylline alone could inhibit the proliferation of fibroblasts and the expression of IL-6 in the Sprague-Dawley rat model of hypertrophic scars, and allantoin-based moisturizer may improve the prognosis of hypertrophic scars.

Key words: Cratrix, Hypertrophic scar, Pentoxifylline, Disease models, animal, Rats, Sprague-Dawley, Fibroblass