益气养阴生肌方对复发性口腔溃疡大鼠的治疗作用及其对黏膜炎症因子和机体免疫功能的影响

目的: 分析益气养阴生肌方对复发性口腔溃疡（ROU）大鼠的治疗作用及其对黏膜炎症因子和机体免疫功能的影响。方法: 选取SPF级Wistar雄性大鼠60只，随机数字表法将大鼠分成6组，分别为益气养阴生肌方低、中、高剂量组、正常组、模型组及阳性对照组，每组各10只，除正常组外其他各组大鼠制备ROU模型，成功造模后，益气养阴生肌方低、中、高剂量组分别给予0.17 mg/kg、0.34 mg/kg、0.68 mg/kg的益气养阴生肌方药液，阳性对照组灌胃布洛芬药液，正常组和模型组灌胃生理盐水，1次/d，连续灌胃10 d。观察各组大鼠溃疡数量、持续、间隔时间及溃疡面积，检测各组大鼠血清白细胞介素-2R（IL-2R）、IL-1β、IL-17、γ-干扰素（IFN-γ）、IL-2、转化生长因子-β1（TGF-β1）、表皮生长因子、血管内皮生长因子（VEGF）及T淋巴细胞含量，同时检测溃疡组织内NLRP3 mRNA相对表达量和基质金属蛋白酶-9（MMP-9）、MMP-2蛋白表达情况。 结果: 给药后2、6、10 d时阳性对照组、益气养阴生肌方中、高剂量组大鼠溃疡面积低于模型组，益气养阴生肌方中、高剂量组溃疡面积低于阳性对照组，差异均有统计学意义（P＜0.05）；和正常组相比，模型组大鼠血清IL-2R、IL-17、IL-1β及IFN-γ含量上升，血清IL-2含量下降；和模型组相比，阳性对照组、益气养阴生肌方中、高剂量组大鼠血清IL-2R、IL-17及IFN-γ含量下降，血清IL-2含量上升，差异均有统计学意义（P＜0.05）；和正常组相比，模型组大鼠血清TGF-β1、EGF含量下降，血清VEGF含量，溃疡组织内NLRP3 mRNA相对表达量及MMP-9、MMP-2蛋白表达量上升；和模型组相比，阳性对照组、益气养阴生肌方中、高剂量组大鼠血清TGF-β1、EGF、VEGF含量上升，溃疡组织内NLRP3 mRNA相对表达量及MMP-9、MMP-2蛋白表达量下降，差异均有统计学意义（P＜0.05）。结论: 益气养阴生肌方可纠正ROU大鼠免疫功能紊乱，降低血清炎症因子含量，以起到治疗作用。

Effects of Yiqi Yangyinshengji recipe on rats with recurrent oral ulcer and its effect on mucosal inflammatory factors and immune function

AIM: To analyze the therapeutic effect of Yiqi Yangyinshengji recipe on rats with recurrent oral ulcer (ROU) and its effect on mucosal inflammatory factors and immune function. METHODS: Sixty Wistar male rats of SPF grade were randomly divided into six groups, namely, low-, medium-, and high-dose groups of Yiqi Yangyinshengji receipe, normal group, model group and positive control group. Each of the 10 rats, except the normal group, was prepared for the ROU model. After successful modeling, the low-, medium-, and high-dose groups of Yiqi Yangyinshengji group was administered with 0.17 mg/kg, 0.34 mg/kg and 0.68 mg/kg Yiqi Yangyinshengji liquid, respectively; positive control group was treated with ibuprofen solution, normal group and model group were given normal saline, once a day, for a continuous gavage of 10 days. The number, duration, interval and ulcer area of rats in each group were observed. Serum interleukin-2R (IL-2R), IL-1β, IL-17 and γ-interferon (IFN-γ) were detected in each group, as well as IL-2, transforming growth factor-β1 (TGF-β1), epidermal growth factor, vascular endothelial growth factor (VEGF) and T lymphocyte content, and relative expression of NLRP3 mRNA and matrix metalloproteinase in ulcer tissue 9 (MMP-9), MMP-2 protein expression. RESULTS: At 2, 6 and 10 days after administration, the area of ulcer in the positive control group, the middle- and high-dose groups of Yiqi Yangyinshengji receipe was lower than that in the model group, and the ulcer area of the middle- and high-dose groups of Yiqi Yangyinshengji receipe was lower than that of the positive control group (P<0.05). Compared with the normal group, the serum IL-2R, IL-17, IL-1β and IFN-γ levels in the model group increased, serum IL-2 content deceased (P<0.05); compared with the model group, the serum levels of IL-2R, IL-17 and IFN-γ in the positive control group, Yiqi Yangyinshengjifang middle and high dose group decreased, serum IL-2 content increased (P<0.05). Compared with the normal group, the serum levels of TGF-β1 and EGF in the model group decreased, serum VEGF content, relative expression of NLRP3 mRNA in ulcer tissues, and MMP-9 and MMP-2 protein expression increased (P<0.05). Compared with the model group, the serum levels of TGF-β1, EGF and VEGF in the positive control group, Yiqi Yangyinshengjifang middle and high dose group increased, and the relative expression of NLRP3 mRNA in ulcer tissue, level of MMP-9 and MMP-2 protein decreased (P<0.05). CONCLUSION: Yiqi Yangyinshengji can improve the immune dysfunction of ROU rats and reduce the serum inflammatory factor content.