清热生肌膏对乳腺癌大鼠放射治疗后急性放射性皮炎发生率、ICM-1及新生血管生成的影响

Effect of Qingre Shengji ointment on the incidence of acute radiation dermatitis, ICM-1 and neovascularization in breast cancer rats after radiotherapy

  • 摘要: 目的:探究清热生肌膏对乳腺癌大鼠放射治疗(放疗)后急性放射性皮炎发生率、细胞间黏附分子-1(ICM-1)及新生血管生成的影响。方法:选取40只SPF级SD雌性大鼠,随机分为正常组(N组),模型组(M组),芦荟凝胶组(A组),清热生肌膏组(H组),每组10只,对M组、A组、H组采用灌胃二甲基苯蒽法建立乳腺癌模型,建模成功后进行放疗,然后在患处对A组直接涂抹芦荟凝胶,对H组直接涂抹清热生肌膏,N组、M组同期给予灌胃同体积生理盐水,计算大鼠急性放射性皮炎发生率,绘制创面发生曲线,HE染色法检测皮肤组织病理形态,蛋白质免疫印迹法检测ICM-1蛋白表达,免疫组化染色及图像分析新生血管生成相关指标。结果:与M 组相比,A 组、H 组急性放射性皮炎发生率降低(P< 0.05),且H 组比A 组降低更为显著(P< 0.05);与M组相比,A组、H组创面发生率曲线显著降低(P< 0.05),且H组比A组降低更为显著(P< 0.05);N组大鼠皮肤组织及成纤维细胞形态正常完整,棘细胞均匀分布,表皮光滑平整,毛囊、皮脂腺、汗腺等附属器发育正常,未见间距增宽或狭窄,M组皮肤表皮凹凸不平,且出现部分脱落,表皮层坏死,真皮层内皮肤附属器消失,结构紊乱,并可见大量大型、畸形的放射性成纤维细胞及大量炎性细胞浸润,可见少量新生血管。与M组相比,H组、A组病理症状明显改善,新生血管生成明显增多;与N组比较,M组受照部位皮肤组织中ICM-1蛋白表达显著升高(P< 0.05),与M组比较,H组、A组受照部位皮肤组织中ICM-1蛋白表达显著降低(P< 0.05),且H 组比A 组降低更为显著(P< 0.05);与N 组比较,M 组新生微血管数量无明显差异(P> 0.05),受照部位皮肤组织中血管内皮生长因子(VEGF)及其受体(VEGFR)灰度值显著升高(P< 0.05),与M组比较,H组、A组新生微血管数量显著升高,受照部位皮肤组织中VEGF、VEGFR灰度值显著降低(P< 0.05),且H组比A组变化更为显著(P< 0.05)。结论:清热生肌膏具有显著疗效,可有效降低乳腺癌大鼠放疗后急性放射性皮炎发生率,降低ICM-1表达,并有效促进新生血管生成。

     

    Abstract: Objective:To investigate the effect of Qingre Shengji ointment on the incidence of acute radiation dermatitis, intercellular adhesion molecule-1 (ICM-1) and neovascularization in rats with breast cancer after radiotherapy.Methods:40 SPF SD female rats were selected and randomly divided into normal group (group N), model group (group M), aloe vera gel group (group A), and Qingre Shengji ointment group (group H), with 10 rats in each group.The breast cancer model of group M, group A and group H was established by inadministration of dimethylbenzanthracene, radiotherapy was given after successful modeling, then aloe vera gel was applied directly to group A, and Qingre Shengji ointment was applied directly to group H on the affected area.Group N and group M were concurrently administered the same volume of normal saline via gastric lavage, the incidence of acute radiation dermatitis of rats was calculated, the wound curve was drawn, the skin tissue pathological morphology was detected by HE staining, the expression of ICM-1 protein was detected by western blotting, and the related indicators of neovascularization were analyzed by immunohistochemical staining and image analysis.Results:Compared with group M, the incidence of acute radiation dermatitis in groups A and H decreased (P< 0.05), and the decrease in group H was significantly greater than that in group A (P< 0.05).Compared with group M, the wound incidence curve of group A and Group H significantly decreased(P< 0.05), and the decrease of group H was significantly greater than group A(P< 0.05).The skin tissues and fibroblasts of rats in group N were normal and complete, the spinous cells were evenly distributed, the epidermis was smooth and flat, the appendages of hair follicles, sebaceous glands, sweat glands and other appendages developed normally, and no widening or narrowing of spacing was observed.The skin epidermis in group M was uneven and partially detached, the epidermis was necrotic, the appendages of the skin in the dermis disappeared, and the structure was disorganized.A large number of large and deformed radioactive fibroblasts and a large number of inflammatory cells were infiltrated, and a small number of neovascularization could be seen.Compared with group M, pathological symptoms were significantly improved in group H and group A, and neovascularization significantly increased.Compared with group N, the expression of ICM-1 protein in the exposed skin tissues of group M significantly increased(P< 0.05), while the expression of ICM-1 protein in the exposed skin tissues of groups H and A significantly decreased compared with group M(P< 0.05), and the decrease in group H was significantly greater than that in group A(P< 0.05).Compared with group N, there was no significant difference in the number of new microvessels in group M(P> 0.05), and the gray value of vascular endothelial growth factor(VEGF)and its receptor(VEGFR)in skin tissues at the exposed site significantly increased(P< 0.05).Compared with group M, the number of new microvessels in groups H and A significantly increased.The gray values of VEGF and VEGFR in the exposed skin significantly decreased (P< 0.05), and the changes in group H were significantly greater than those in group A(P< 0.05).Conclusion:Qingre Shengji ointment is effective in reducing the incidence of acute radiation dermatitis, reducing the expression of ICM-1 and promoting neovascularization in breast cancer rats after radiotherapy.

     

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