高分子量玻尿酸对大鼠膝骨关节炎滑膜细胞炎症因子和趋化因子的影响

Effect of high molecular weight hyaluronic acid on inflammatory cytokines and chemokines of synoviocytes isolated from SD mouse

目的：探讨高分子量玻尿酸（HA）是否可以抑制膝骨关节炎（OA）滑膜细胞中炎症因子和趋化因子的表达。方法：从大鼠木瓜酶诱导OA分离滑膜细胞，使用IL-1进行炎性刺激（或不刺激），并用600～800kDa分子量的HA进行干预，探讨炎症因子和趋化因子的表达。并观察应用CD44抗体阻滞后，这些基因的表达情况。此外。应用Tunel法检测滑膜细胞凋亡。结果：HA降低了未刺激滑膜细胞中MMP-3、CX3CL1和CCL2的表达以及IL-1刺激滑膜细胞中TNF—α、MMP．3、CX3CL1和CCL2的表达。CD44阻滞抑制了HA下调这些因子的效应．HA可以促进滑膜细胞在炎症状态下凋亡。结论：HA可以抑制OA滑膜TNF-α、MMP-3、CX3CL1以及CCL2，具有潜在的抗炎效应，且能促进炎症状态下滑膜细胞的凋亡。这些效应可能通过HA与CD44交互作用而产生。

Objective To investigate whether HA affects the inflammatory cytokines and chemokines of synovioeytes. Methods FLS were derived from the SD mice with knee OA by papaya enzyme and stimulated by IL-1. Then, FLS were cultured with 600 - 800 kDa HA. Anti-CD44 blocking experiments were determined. The expressionsof TNF-γ, IL-1, IL-6, MMP-3, MMP-9, CX3CLI, CCL11, CCL2, CXCL12 were detected by RT- PCR. In addition, the tunel test was used to detect the apoptosis rate. Results MMP-3, CX3CL1 and CCL2 gene expression were down regulated by HMW-HA in unstimulated FLS and TNF-α, MMP-3, CX3CL1 and CCL2 expression were decreased by HMW-HA in IL-1-stimulated FLS. CD44 blocking inhibited the down-regulatory effects of HMW-HA. Besides, HMW-HA promoted cell apoptosis under condition of inflammation. Conclusion HMW-HA has an anti-inflammatory effect by down-regulating of pro-inflammatory eytokines and chemokines and promoting apoptosis, possibly through the interaction of CD44 and HMW-HA.