回阳生肌脂质体凝胶促进慢性皮肤溃疡大鼠创面愈合机制的研究

Mechanism of Huiyangshengji Liposome Gel in promoting healing of chronic skin ulcer in rats

目的观察回阳生肌脂质体凝胶促进慢性皮肤溃疡愈合的作用,探讨其治疗阴证疮疡的药理机制。方法SD大鼠80只随机分为4组:正常组、模型组、传统回阳生肌膏治疗组(传统组)和回阳生肌脂质体凝胶治疗组(脂质体组)。采用"激素干预-皮肤缺损-细菌感染"复合因素叠加法制备慢性皮肤溃疡大鼠模型。观察大鼠一般生活行为,检测大鼠血清肿瘤坏死因子-α(TNF-α)及白细胞介素-8(IL-8)含量,免疫组化法检测疮疡区组织中增殖细胞核抗原(PCNA)和血管内皮生长因子(VEGF)表达,并行图像分析。结果与正常组比较,模型组大鼠血清中TNF-α和IL-8含量显著升高,溃疡区组织中PCNA表达增多、VEGF表达减少(P<0.05)。与模型组比较,脂质体组大鼠血清中TNF-α和IL-8含量均呈下降的趋势(P<0.05或P<0.01)。脂质体组大鼠溃疡面可见丰富的新生毛细血管且向伤口处聚集分布,VEGF在再生的血管壁胞浆表达阳性,真皮层中见到较多PCNA阳性细胞,而且还在新生血管内皮细胞中可见到棕黄色颗粒表达。与模型组比较,脂质体组PCNA和VEGF表达均有统计学差异(P<0.05)。结论回阳生肌脂质体凝胶具有促进慢性皮肤溃疡愈合的作用,其作用机制可能与该药促进慢性皮肤溃疡创面细胞增殖、调动血管内皮生长因子参与血管再生、减轻机体炎症反应有关。

Objective To observe the effect of Huiyangshengji Liposome Gel in promoting healing of chronic skin ulcer, and discuss its Methods SD rats （ n = 80） were pharmacologic mechanism in the randomly divided into 4 groups, treatment of ulcer of yin-syndrome. including the normal group, model group, treatment group of Huiyangshengji Plaster （traditional group ） and treatment group of Huiyangshengji Liposome Gel （liposome group）. The rat model of chronic skin ulcer was established by applying complex factor superposition method of dehydrocortisone, skin defects and bacterial infection. The life behaviors were observed experimentally, and the serum contents of tumor necrosis factor-α （TNF-α） and interleukin-8 （IL-8） were detected. The expressions of proliferating cell nuclear antigen （PCNA） and vascular endothelial growth factor （VEGF） in ulcer tissue were detected by immunohistochemistry assay and analyzed by imaging technique. Results In the model group the serum contents of TNF-α and IL-8 increased significantly, PCNA expression increased, and VEGF expression decreased in ulcer tissue （P 〈 0.05） than those in the normal group. In the liposome group, compared with the model group, the serum contents of TNF-α and IL-8 trended to decrease （P 〈0.05 or P 〈0.01 ）, a lot of new capillaries aggregated around ulcer, VEGF expression was positive in vessel wall cytoplasm, many PCNA positive cells were seen in the corium, and the expression of brown granules were observed in new vascular endothelial cells. The expressions of PCNA and VEGF was different statistically between the liposome group and model group （P 〈0.05）. Conclusion Huiyangshengjigao Liposome Gel can promote the healing of chronic skin ulcer through improving the proliferation of ulcer cells, arousing VEGF involving vessel regeneration, and relieving the inflammatory reaction.