白芍总苷对实验性关节炎大鼠足爪组织基质金属蛋白9表达及关节浸液一氧化氮和地诺前列酮水平的影响

目的探讨白芍总苷(TGP)对大鼠胶原性关节炎治疗的可能机制。方法采用鸡胶原Ⅱ型制备实验性关节炎(CIA)大鼠模型,造模后第7~27天ig给予TPG 25,50和100 mg·kg-1。观察CIA大鼠关节指数,体质量变化及足爪组织病理学变化,免疫组化法测定大鼠足爪组织中基质金属蛋白酶9(MMP-9)的表达,采用硝酸还原法和放免法测定关节浸液中一氧化氮(NO)和地诺前列酮(前列腺素E2,PGE2)含量。结果与模型组相比,TGP可明显降低关节指数(P<0.05),且TGP50和100 mg.kg-1可有效缓解CIA模型大鼠体质量减轻(P<0.01);TGP 50和100 mg·kg-1组足爪组织MMP-9表达明显降低(P<0.05);与模型组相比,TGP还可明显降低CIA大鼠关节浸液中NO和PGE2含量(P<0.05)。结论 TGP对大鼠实验性关节炎有明显抑制作用,其作用机制可能与其下调MMP-9表达、抑制炎症局部区域相关炎症介质产生有关。

Effect of total glucosides of paeonia on matrix metalloproteinase 9 protein expression and nitric oxide and dinoprostone in collagen-induced arthritis rats

OBJECTIVE To explore the effect of total glucosides of paeonia (TGP) on the treatment of collagen-induced arthritis (CIA) in rats and its possible mechanism. METHODS A CIA model in SD rats was induced by collagen typeⅡ. Rats articular index, body mass change and the histopathology in their paws skin were observed. The expression of matrix metalloproteinase 9 (MMP- 9) protein in rats paw tissues was detected by immunohistochemical staining. The content of NO were detected by nitrate content determination, and the content of dinoprostone (prostaglandin E₂, PGE₂) by radioimmunoassay. RESULTS Compared with CIA model group, TGP could inhibit the swelling of CIA rats paw and decrease articular index (P<0.05). TGP 50 and 100 mg·kg^-1 could effectively relieve the weight loss of CIA rats (P<0.01). The MMP- 9 expression was significantly lower in TGP 50 and 100 mg·kg^-1 groups (P<0.05）, TGP could also significantly decrease the content of NO and PGE₂ in articular infusion levels (P<0.05). CONCLUSION TGP has obvious inhibition on CIA rats and the mechanism may be related to decreased the expression of MMP-9 protein, and the generation of inflammation-related inflammatory mediators and inhibited activity of endogenous inflammatory cytokines.