芍药苷—阿魏酸共载传递体凝胶对佐剂性关节炎大鼠的治疗作用及机制研究

Therapeutic effect and mechanism of paeoniflorin-ferulic acid co-loaded transfersome gel on adjuvant arthritis rat

目的:研究芍药苷-阿魏酸共载传递体凝胶(paeoniflorin-ferulic acid co-loaded transfersome gel, PFCTG)对弗氏完全佐剂(Freund′s complete adjuvant, FCA)诱导佐剂性关节炎(adjuvant arthritis, AA)大鼠的治疗作用及机制。方法:建立FCA诱导的AA大鼠模型。试验动物分为空白对照组、模型组、阳性组、PFCTG低、中、高剂量组。测定大鼠给药前后的体质量、关节炎指数(adjuvant arthritis, AI)、原发侧足跖肿胀度、脏器指数、血清中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、类风湿因子(RF)水平;采用苏木精-伊红(HE)染色法观察大鼠病理组织变化;采用免疫组化法检测大鼠踝关节组织的基质金属蛋白酶-3(MMP-3)、血管内皮生长因子(VEGF)的阳性表达水平。结果:与空白对照组相比,模型组AI评分、足跖肿胀度显著增大(P<0.01);脏器指数高于空白对照组,但差异无统计学意义(P>0.05);血清中IL-1β、IL-6、TNF-α、RF含量显著性升高(P<0.01);关节软骨偶见血管翳,表面被覆少量结缔组织,关节滑膜轻度增生,滑膜有炎性细胞浸润现象;踝关节MMP-3与VEGF阳性表达明显增强。与模型组相比,PFCTG与阳性药干预后,能显著降低大鼠AI评分、足跖肿胀度以及血清中IL-1β、IL-6、TNF-α、RF含量(P<0.01,P<0.05),并可以明显改善关节软骨损坏程度,下调大鼠踝关节MMP-3与VEGF的阳性表达。结论:PFCTG局部外用对佐剂性关节炎大鼠具有明显的治疗作用,其机制可能与下调IL-1β等因子水平、调控MMP-3与VEGF的阳性表达有关。

OBJECTIVE To investigate the therapeutic effects and mechanisms of paeoniflorin-ferulic acid co-loaded transfersome gel(PFCTG)on Freund′s complete adjuvant(FCA) induced adjuvant arthritis(AA) in rats.METHODS The AA rat modelinduced by FCA was established.Experimental animals were divided into blankcontrol group, model group, positive group, low-dose, medium-dose and high-dose PFCTGgroups.Body weight, arthritis index(AI),primary lateral foot swelling, viscera index, serum interleukin-1 β(IL-1β),interleukin-6(IL-6),tumornecrosis factor α(TNF-α) and rheumatoid factor(RF) of rats before and afteradministration were determined.The pathological changes of rats were observed byhematoxylin-eosin(HE) staining.The positive expression levels of matrixmetalloproteinase-3(MMP-3) and vascular endothelial growth factor(VEGF) in the ankle tissues of rats were detected by immunohistochemical method.RESULTS Compared with blank control group, the AI score and the foot swelling degree in model group were significantly increased(P<0.01),the organ index was higher than that of blank control group, but the difference was not statistically significant(P>0.05),the contents of IL-1β,IL-6,TNF-α and RF in serum were significantly increased(P<0.01);pannus was occasionally seen in articular cartilage, the surface was covered with a small amount of connective tissue, the synovial membrane of the joint was mildly hyperplasia with inflammatory cell infiltration.The positive expression of MMP-3 and VEGF in ankle joint was significantly enhanced.Compared with the model group, the intervention of PFCTG and positive drugs could significantly reduce the AI score, the degree of the swelling in rats, and the contents of IL-1β,IL-6,TNF-α and RF in serum(P<0.01,P<0.05).In addition, they can significantly improve the damage degree of articular cartilage and down-regulate the positive expression of MMP-3 and VEGF in the ankle joint of rats.CONCLUSION Topical application of PFCTG has obvious therapeutic effect on adjuvant arthritis rats, and its mechanism may be related to down-regulating the levels of factors such as IL-1β and regulating the positive expression of MMP-3 and VEGF.