新癀片调节抗炎镇痛相关基因的初步研究

Regulation of anti-inflammation and analgesic genes by Xinhuang tablets

目的利用基因芯片技术分析新癀片的抗炎镇痛作用机制,在基因水平上寻找药物作用的靶点通路。方法选用SD雄性大鼠,随机分为对照,模型,吲哚美辛,新癀片高、中、低剂量组。除对照组外,在大鼠右后足垫部皮下注射角叉菜胶浆致炎造模。测定致炎前后踝关节处肿胀度,测定鼠足自照射至出现抬足动作的时间,随后剖杀大鼠取肝脏,进行基因组学研究。结果 1新癀片能明显抑制角叉菜胶引起的大鼠足肿,显著延长光热刺激导致的大鼠抬足反应潜伏期,表明新癀片有显著的抗炎镇痛作用;2基因芯片结果显示,新癀片能够显著上调P2rx5、Npy2r等基因;显著下调Hspa14、Il15、Myd88、Kng1//Kng1l1、Nfkbiz、Rasa1、Ubd等基因。结论新癀片主要通过抑制NF-κB通路的激活发挥抗炎镇痛作用:下调髓样分化因子88(My D88)和IκBζ的基因表达抑制泛素D(Ubd)的基因表达;对热休克蛋白14(Hspa14)的基因表达下调等;这些因素均会使NF-κB的激活受到抑制。新癀片能够明显拮抗谷氨酰胺酶(Gls)和激肽原1(Kng1///Kng1l1),进一步发挥镇痛抗炎作用。与吲哚美辛比较,新癀片影响的基因靶点更多。

Objective To study the anti-inflammatory and analgesic mechanism of Xinhuang tablets by gene chip technology and drug targeting pathways in the gene levels. Methods SD rats were randomly divided into 6 groups： a control group, a model group, an indomethacin group, and Xinhuang tablets high dose, medium dose and low dose groups. Except for the control group, carrangeenan was injected subcutaneously into the right footpad of rats to induce inflammation in all groups. Afterwards the reseachers measured the swelling degrees around the ankles, and the time of foot movements after irradiation. The rats were sacrificed and livers obtained for genomics research. Results （1） The foot swellings were significantly inhibited by Xinhuang tablets, and the response latency of lifting foot was prolonged. Xinhuang tablets showed significant anti-inflammation and analgesic effects. （2 ）The gene chip showed that Xinhuang tablets up-regulated the expression of P2rx5, Npy2r gene; and down-regulated heat shock protein 14 （Hspa14）, Il15, myeloid differentiation factor 88 （MyD88）, Nfkbiz, Rasal, kininogen 1 （Kng1///Kngll1）, ubiquitin D （Ubd） genes and so on. Conclusion The anti-inflammatory and analgesic effects of Xinhuang tablets are shown mainly by inhibiting the pathway of NF-xB activation. It can down-regulate the gene expression of MyD88 and Ikdζ, inhibit the gene expression of Ubd, and down-regulate the genes level of Hspa14. The mentioned factors can all lead to the inhibition of NF-xB activation. Xinhuang tablets can significantly antagonize the expression of glutaminase （Gls） and Kng1///Kngll1. Xinhuang tablets have more gene targets than indomethacin.