环孢菌素纳米胶体治疗复发性口腔溃疡大鼠的效果

Effect of cyclosporine nanogel on recurrent oral ulcer in rats

目的探讨环孢菌素纳米胶体治疗复发性口腔溃疡(ROU)大鼠的效果。方法将55只SD大鼠随机分为空白组、模型组、环孢菌素A(Cy A)纳米胶体高、中、低剂量组,每组11只,空白组不给予处理,其余各组采用免疫法建立大鼠ROU模型、于建模结束后第7天,Cy A纳米胶体高、中、低剂量组分别给予1.5 mg/ml、1.0 mg/ml、0.05 mg/ml的Cy A纳米胶体灌胃,空白组及模型组给予等体积的生理盐水灌胃,连续给药10 d。给药第5天时检测各组5只大鼠外周血CD4^+、CD8^+细胞比例及CD4^+/CD8^+比值、肿瘤坏死因子(TNF)-α、白介素(IL)-2、IL-6的水平;给药第6天时取各组织大鼠黏膜组织观察病理学变化情况;建模后隔天测量各组5只大鼠溃疡面积。结果各剂量Cy A纳米胶体组大鼠口腔溃疡黏膜充血水肿症状较模型组减轻,溃疡面积明显减小,其中高剂量组的症状轻于低剂量组;模型组大鼠外周血CD4^+细胞比例低于其余4组(P<0.05),且纳米胶体Cy A高剂量组CD4^+细胞比例及CD4^+/CD8^+比值均高于中、低剂量组(均P<0.05);各剂量Cy A纳米胶体组TNF-α、IL-2、IL-6水平均低于模型组,其中高剂量组均低于中、低剂量组(均P<0.05)。结论 Cy A纳米胶体可促进大鼠ROU愈合,其中高剂量的治疗效果最佳,可能与调节T淋巴细胞亚群比例和TNF-α、IL-2、IL-6的表达有关。

Objective To investigate the effect of cyclosporine nanogel on recurrent oral ulcer（ ROC） in rats. Methods Fifty-five SD rats were randomly divided into blank group,model group,high-,medium-and low-dose cyclosporine A（ CyA） nanogel group,with 11 rats in each group. Except for the blank group,all groups used immunization to establish the rat model of ROC. On the 7 th day of successful modeling,the high-,medium-and low-dose CyA nanogel groups were given 1. 5,1. 0 and 0. 05 mg/ml CyA nanogel by gavage respectively,while the blank group and model group were given the equivalent volume of normal saline by gavage. All groups received consecutive administered for 10 days. On the 5 th day of administration,the percentages of peripheral blood CD4^＋and CD8^＋cells,the ratio of CD4^＋/CD8^＋,as well as the levels of tumor necrosis factor（ TNF）-α,interleukin（ IL）-2 and IL-6 were detected in 5 rats of each group. The pathological changes of mucosal tissues from various rat tissue specimens were observed on the 6 th day of administration. And the area of ulcer was measured in 5 rats of each group every other day after modeling. Results Compared to the model group,the CyA nanogel groups presented milder oral ulcer with mucosal hyperemia and edema and significantly decreased ulcer area,and the medium-and high-dose groups ochieved less severe symptoms compared to the low-dose group; the percentage of peripheral blood CD4^＋cells in the model group was lower than that in the other 4 groups（ P〈0. 05）,and the percentage of CD4^＋cells and the ratio of CD4^＋/CD8^＋in the high-dose CyA nanogel group were higher than those in the medium-and low-dose groups（ all P〈0. 05）; the levels of TNF-α,IL-2 and IL-6 in the CyA nanogel groups were lower than those in the model group,and the levels in the high-dose CyA nanogel group were lower than those in the medium-and low-dose groups（ all P〈0. 05）. Conclusion CyA nanogel can promote ROC healing in rats,and high dose of CyA nanogel obtains the optimal efficacy,which may be related to regulating the percentage of T lymphocyte subsets as well as the levels of TNF-α,IL-2 and IL-6.