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目的探讨曲尼司特对小鼠烧伤创面愈合时间的影响及其抑制瘢痕增生的作用机制,以及曲尼司特抑制瘢痕增生的能力是否随给药时间点变化而变化。方法 7~8周龄清洁级雄性昆明小鼠66只,于小鼠背部制备深Ⅱ度烧伤模型,然后随机分为对照组(n=18)、早期干预组(n=18)、中期干预组(n=18)和晚期干预组(n=12)。早、中、晚期干预组分别于造模后当天、7 d、14 d开始给予曲尼司特200 mg/(kg·d)灌胃,对照组于造模后当天开始每天给予等体积生理盐水灌胃。定期观察创面愈合情况,对照组及早、中期干预组分别于造模后14、28、42 d,晚期干预组于28、42 d,随机选取6只小鼠取创面新生组织,分别行甲苯胺蓝染色观察肥大细胞形态,Masson染色观察总胶原含量情况;行免疫组织化学染色观测Ⅰ型胶原及Ⅲ型胶原含量,并计算Ⅰ/Ⅲ型胶原含量比值;ELISA法检测组织中TGF-β_1和组胺含量;透射电镜观察成纤维细胞的超微结构。结果各组小鼠创面愈合时间比较差异无统计学意义(F=1.105,P=0.371)。早期干预组各时间点肥大细胞数、总胶原含量、Ⅰ/Ⅲ型胶原含量比值、TGF-β_1含量及组胺含量均显著低于其他组(P<0.05);除42 d时对照组肥大细胞数、总胶原含量、组胺含量与晚期干预组比较差异无统计学意义(P>0.05)外,其余各时间点对照组及中、晚期干预组间以上指标比较差异均有统计学意义(P<0.05)。与对照组相比,早期干预组成纤维细胞活跃程度明显被抑制,纤维排列更加规律整齐;中、晚期干预组成纤维细胞活性亦较明显被抑制。结论曲尼司特干预对小鼠烧伤创面愈合时间无明显影响,但能明显降低新生组织中肥大细胞、组胺和TGF-β_1含量,抑制成纤维细胞胶原合成能力及调节胶原合成的比值,从而抑制瘢痕增生,且烧伤后即刻进行曲尼司特干预对瘢痕增生的抑制作用最明显。
Objective To investigate the effect of tranilast on wound healing time and its mechanism of inhibiting scar proliferation in mice, and whether the ability of tranilast to inhibit scar hyperplasia changes with time. Methods Sixty-six male Kunming mice, aged 7-8 weeks old, were randomly divided into control group (n = 18), early intervention group (n = 18), middle-term intervention group (n = 18) and late intervention group (n = 12). Tranilast 200 mg / (kg · d) was given to the early, middle and late intervention groups on the day of model making, 7 d and 14 d respectively. The control group was given an equal volume of normal saline Gavage. Periodontal wound healing was observed. In the early and mid-term intervention groups, 14,28 and 42 d after modeling, and 28 and 42 d in the late intervention group, 6 mice were randomly selected to take new tissue from the wounds. Toluidine blue The morphology of mast cells was observed by staining and the total collagen content was observed by Masson staining. The contents of type I collagen and collagen Ⅲ were observed by immunohistochemical staining, and the ratio of type Ⅰ / Ⅲ collagen was calculated. The levels of TGF-β 1 and histamine Content; TEM observation of the ultrastructure of fibroblasts. Results There was no significant difference in wound healing time between the two groups (F = 1.105, P = 0.371). In the early intervention group, the number of mast cells, the total collagen content, the collagen Ⅰ / Ⅲ ratio, the TGF-β 1 content and the histamine content in the early intervention group were significantly lower than those in the other groups (P <0.05) (P> 0.05), while there was no significant difference between the control group and the middle and late intervention groups at all time points (P> 0.05) <0.05). Compared with the control group, the activity of fibroblasts in early intervention group was significantly inhibited, and the fiber arrangement was more regular and neat. The activity of fibroblasts in middle and late intervention group was also significantly inhibited. Conclusion Tranilast intervention had no significant effect on healing time of burn wounds in mice, but significantly reduced the content of mast cells, histamine and TGF-β 1, inhibited the collagen synthesis ability of fibroblasts and the ratio of collagen synthesis in neonatal tissues Inhibition of scar hyperplasia, and trastuzumab immediate intervention on scar hypertrophy inhibition most obvious.