柚皮苷抑制胶原诱导小鼠关节炎症作用机制的实验研究

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目的检测柚皮苷干预后胶原诱导(CIA)小鼠关节炎症相关指标的变化。方法选择雄性DBA1/J小鼠35只,随机分为正常组(5只)和实验组(30只)。实验组炎症评分达2分以上再分为骨碎补组(10只)、CIA模型组(10只)、柚皮苷组(10只)。各组均以灌胃方式给药,每天1次,连续20次。给药20 d后处死小鼠,ELISA方法测定小鼠血清中IL-6、TNF-α的水平,HE染色观察滑膜炎症表达情况,免疫组化法检测小鼠膝关节滑膜组织中HIF-1α、CXCR4蛋白的表达情况。结果给药第11天开始,柚皮苷组炎症评分低于CIA模型组,差异有统计学意义(P<0.05);给药第15天开始,柚皮苷组与骨碎补组炎症评分均低于CIA模型组,差异有统计学意义(P<0.05);给药第19天,骨碎补组与柚皮苷组炎症评分均有降低表现,且柚皮苷组炎症评分较骨碎补组低,差异有统计学意义(P<0.05)。柚皮苷、骨碎补组较CIA模型组的IL-6、TNF-α水平均下降,差异有统计学意义(P<0.01)。柚皮苷组的IL-6水平较骨碎补组低,TNF-α水平较骨碎补组高,但差异无统计学意义(P>0.05)。柚皮苷组HIF-1α、CXCR4的IOD值低于CIA模型组,差异有统计学意义(P<0.05);骨碎补组HIF-1α、CXCR4的IOD值与CIA模型组比较差异无统计学意义(P>0.05);骨碎补组与柚皮苷组2组间差异无统计学意义(P>0.05)。柚皮苷、骨碎补组染色阳性区域Area值均低于CIA模型组,差异有统计学意义(P<0.05);骨碎补组与柚皮苷组2组间比较差异无统计学意义(P>0.05)。结论柚皮苷对HIF-1α上游的炎症因子IL-6、TNF-α及下游的CXCR4都具有一定调控作用,显著的降低了CIA小鼠炎症反应。 Objective To detect the change of joint inflammation related to collagen induced (CIA) mice after naringin intervention. Methods Thirty-five male DBA1 / J mice were randomly divided into normal group (n = 5) and experimental group (n = 30). The inflammatory score of the experimental group was up to 2 points and then divided into two groups: the Niaodubu group (10), the CIA model group (10) and the naringin group (10). Each group were given intragastric administration, 1 times a day for 20 times. Mice were sacrificed 20 d after the administration, the levels of IL-6 and TNF-α in serum were determined by ELISA, the synovial inflammation was observed by HE staining, the expression of HIF-6 in synovium of knee joint was detected by immunohistochemistry, 1α, CXCR4 protein expression. Results The inflammatory score of naringin group was lower than that of CIA model group on the 11th day after administration (P <0.05). From the 15th day after administration, the inflammation scores of naringin group and rhubarb supplement group (P <0.05). On the 19th day after administration, the inflammation scores of both nbr defrosinone group and naringin group were lower than those of CIA group Group was lower, the difference was statistically significant (P <0.05). Naringin and Rhizoma Drynariae decreased the levels of IL-6 and TNF-α in CIA model group, with statistical significance (P <0.01). The level of IL-6 in naringin group was lower than that in xiaobufu group, and the level of TNF-α was higher than that in xufubu group, but the difference was not statistically significant (P> 0.05). The IOD values ​​of HIF-1α and CXCR4 in naringin group were lower than those in CIA model group (P <0.05), while the IOD values ​​of HIF-1α and CXCR4 in naringin group were not statistically different from CIA model group (P> 0.05). There was no significant difference between the two groups (P> 0.05). Naringin and nibsia group were lower than that of CIA model group (P <0.05), and there was no significant difference between the two groups P> 0.05). Conclusion Naringin can regulate the inflammatory cytokines IL-6, TNF-α and CXCR4 downstream of HIF-1α, and significantly reduce the inflammatory reaction in CIA mice.
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