泄浊解毒方对急性痛风性关节炎大鼠血清IL-1β、TNF-α、MMP-3的影响

Effects of Xiezhuo Jiedu Fang(泄浊解毒方) on Serum IL-1β,TNF-α and MMP-3 in Acute Gouty Arthritis Model Rats

目的探讨泄浊解毒方治疗急性痛风性关节炎的可能作用机制。方法将100只Wistar大鼠随机分为空白组、模型组、秋水仙碱组、泄浊解毒方低剂量组、泄浊解毒方高剂量组,每组20只。秋水仙碱组每日给予0.1 mg/ml秋水仙碱混悬液2 ml灌胃,泄浊解毒方高、低剂量组每日分别给予含生药量24.7、6.175 g/L的泄浊解毒方中药混悬液2 ml灌胃,空白组和模型组每日给予2 ml生理盐水灌胃。各组均灌胃10天,每天1次。除空白组外,其余各组于灌胃第4天采用单尿酸钠晶体溶液注射大鼠右后侧膝关节制备急性痛风性关节炎模型。造模后5、10、24、48、72 h测量大鼠膝关节肿胀度,计算关节肿胀指数。测定各组大鼠血清白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)、基质金属蛋白酶3(MMP-3)含量。结果与空白组比较,其余各组各时间点膝关节肿胀指数均增大(P<0.01)。与模型组比较,造模10、24、48、72 h秋水仙碱组及泄浊解毒方低、高剂量组膝关节肿胀指数均减小(P<0.01)。与泄浊解毒方低剂量组比较,泄浊解毒方高剂量组造模10、24、48、72 h膝关节肿胀指数均减小(P<0.01)。与空白组比较,其余各组大鼠血清IL-1β、TNF-α、MMP-3含量均升高(P<0.01);与模型组比较,秋水仙碱组及泄浊解毒方高、低剂量组大鼠血清IL-1β、TNF-α、MMP-3含量均降低(P<0.01);泄浊解毒方高剂量组大鼠血清IL-1β、TNF-α、MMP-3含量低于泄浊解毒方低剂量组(P<0.01)。结论泄浊解毒方能显著减轻急性痛风性关节炎大鼠膝关节肿胀,且以高剂量效果最佳,降低血清IL-1β、TNF-α、MMP-3含量可能为其作用机制之一。

Objective To explore the possible mechanism of Xiezhuo Jiedu Fang（泄浊解毒方,XZJDF） in the treatment of acute gouty arthritis. Methods A total of 100 Wistar rats were randomly divided into blank group,model group,colchicine group,low dose XZJDF group and high dose XZJDF group,with 20 rats in each group.Colchicine group was given intragastric administration of 2 ml colchicine solution,0. 1 mg/ml,once a day. Low dose and high dose XZJDF group were given daily intragastric administration of 2 ml Xiezhuo Jiedu Fang suspension contenting herbs 24. 7 g/L and 6. 175 g/L respectively. The blank group and model group were given daily intragastric administration of 2 ml normal saline. The intragastric administration last for 10 days,once a day. Apart from the blank group,the rats of other groups were injected with single uric acid sodium crystal solution into the right posterior knee to establish animal model of acute gouty arthritis. The knee joint swelling degree was measured at 5,10,24,48,and72 h after modeling,and the joint swelling index was calculated. Serum levels of interleukin-1β（IL-1β）,tumor necrosis factor α（TNF-α） and matrix metalloproteinase 3（MMP-3） were measured in each group. Results Compared with the blank group,the knee joint swelling index of other groups increased at each time point（P〈0. 01）.Compared with the model group,the knee joint swelling index of the colchicine group and the low and high-dose XZJDF group were decreased at 10,24,48,and 72 h after modeling（P〈0. 01）. Compared with the low-dose XZJDF group,the swelling index of knee joints in the high-dose XZJDF group was decreased at 10,24,48,and 72 h after modeling（P〈0. 01）. Compared with the blank group,the levels of serum IL-1β,TNF-α and MMP-3 in the other groups were increased（P〈0. 01）. Compared with the model group,the colchicine group,high dose and low dose XZJDF group were decreased（P〈0. 01）. The levels in the high dose XZJDF group were lower than those in the low dose XZJDF group（P〈0. 01）. Conclusion XZJDF can significantly reduce knee joint swelling in rats with acute gouty arthritis,and it is best to use high dose. Lowering serum IL-1β,TNF-α and MMP-3 may be one of its mechanisms.