苦参凝胶对小鼠慢性湿疹的治疗作用

The treatment of chronic eczema in mice by matrine hydrogels

目的制备并表征载苦参碱泊洛沙姆水凝胶,探究其对小鼠皮肤慢性湿疹的治疗作用。方法以泊洛沙姆407、188为基质制备苦参凝胶,采用流变仪表征苦参凝胶黏弹性质。通过检测耳部肿胀度、质量差,血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)含量,以及通过对小鼠耳部组织病理切片、蛋白酶活化受体-2(PAR-2)免疫组织化学切片的观察,考察苦参凝胶对小鼠皮肤慢性湿疹的治疗作用。结果苦参凝胶流动性、铺展性良好,在皮肤表面可快速形成透明、有黏性的均一凝胶制剂。与正常组相比,模型组小鼠在慢性湿疹模型建立后的3、5和10 d耳部质量差、肿胀度明显增高(P<0.05);与模型组相比,苦参凝胶组小鼠慢性湿疹导致的耳部质量差、肿胀度明显降低(P<0.01),血清中促炎因子TNF-α、IL-6的水平明显降低(P<0.01),慢性湿疹组织中PAR-2的表达也明显降低(P<0.01,P<0.05)。结论苦参凝胶对慢性湿疹所致的表皮层损伤、真皮层炎性浸润均有一定的治疗作用,有望成为一种良好的治疗皮肤慢性湿疹的外用凝胶制剂。

Objective To prepare and characterize the matrine-loaded poloxamer hydrogels and explore their therapeutic ef⁃fect on chronic eczema in mice.Methods The matrine hydrogels were prepared with poloxamer 407 and 188 as matrix.The viscoelas⁃ticity of the matrine hydrogels was characterized by rheometer.The ear swelling and weight difference were tested,and the levels of tu⁃mor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by ELISA method.The histopathological change of mouse ear tissues was examined via HE-staining,and the immunohistochemical examination was performed to detect the protease-activated re⁃ceptor-2(PAR-2)expression in mouse ear.These assays were performed to investigate the therapeutic effect of matrine hydrogels on chronic eczema in mice.Results The matrine hydrogels had good fluidity and spreadability,and rapidly formed a transparent,vis⁃cous uniform hydrogel at the skin temperature.Compared with the normal group,the ear weight difference and swelling degree were significantly increased(P<0.05)at the 3,5 and 10 days after the establishment of the chronic eczema model.Compared with the mod⁃el group,the ear weight difference and swelling degree were reduced significantly in the martrine hydrogel group(P<0.01),and the serum TNF-αand IL-6 level(P<0.01)and the PAR-2 expression in the chronic eczema tissue(P<0.01,P<0.05)were both signifi⁃cantly decreased in the martrine hydrogel group.Conclusion Martrine hydrogels could inhibit the inflammatory infiltration of dermal layer and the epidermal layer damage caused by chronic eczema,which are expected to be a good topical gel preparation for treating chronic eczema of skin.