雌性红莱菔对急性痛风性关节炎模型大鼠抗炎作用及激活TLR/MyD88/IL-1β信号通路作用机制的研究

Anti-inflammatory Effect of Female Red Radish on Model Rats with Acute Gouty Arthritis and Its Mechanism of Activating Signal Pathway TLR/MyD88/IL-1β

目的:通过TLR/MyD88/IL-1β信号通路探讨雌性红莱菔对尿酸钠致急性痛风性关节炎(AGA)模型大鼠的抗炎作用机制。方法:通过大鼠右踝胫跗关节注射尿酸钠结晶溶液(MSUC),建立AGA大鼠模型,雌性红莱菔低、中和高剂量组和依托考昔组给予相应剂量药物灌胃,空白对照组、模型对照组给予等量的生理盐水灌胃,每日1次,疗程5 d。末次灌胃1 h后,采血分离血清及大鼠右踝胫跗关节组织固定包埋。免疫组化法检测AGA模型大鼠白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)含量;HE染色及免疫组化技术检测大鼠踝关节滑膜组织的病理变化、滑膜肥大细胞数量及活化状态变化、P物质阳性神经纤维数量和Toll样受体2(TLR2)、Toll样受体4(TLR4)、髓样分化因子88(MyD88)分子的表达。结果:雌性红莱菔各剂量组可依剂量变化相应地降低AGA模型大鼠IL-1β、TNF-α水平(P<0.01)。雌性红莱菔各剂量组可依剂量变化相应地降低AGA模型大鼠滑膜部位肥大细胞数量、活化肥大细胞数量及脱颗粒百分率(P<0.01)。雌性红莱菔各剂量组可依剂量变化相应地降低AGA模型大鼠滑膜P物质阳性神经纤维的分布密度(P<0.01)。雌性红莱菔各剂量组可依剂量变化相应地降低AGA模型大鼠关节滑膜组织中TLR2、TLR4和MyD88分子表达(P<0.01)。结论:雌性红莱菔能够减轻AGA模型大鼠踝关节的炎症反应;滑膜部位肥大细胞活化及P物质免疫反应阳性神经纤维可能参与痛风性关节炎的炎症反应及疼痛传导;雌性红莱菔可通过降低TLR/MyD88/IL-1β通路分子的表达发挥其抗炎作用。

Objective:Through signal pathway TLR/MyD88/IL-1β,to explore the anti-inflammatory mechanism of female red radish on acute gouty arthritis(AGA)model rats induced by sodium urate.Methods:AGA rats models were established by injecting mono sodium urate crystal(msuc)solution into the tibiotarsal joints of the right ankles of rats.Rats in the low,medium and high dose groups of female red radish and the etocoxib group were given corresponding doses experimental drugs by gavage once a day.The blank control group and model control group were given the same amount of normal saline by gavage.Five days as a course of treatment.One hour after the last gavaging,the blood was taken to separate the serum and the tissue of the tibiotarsal joints of the right ankles of rats were fixed and embedded.The contents of IL-1βand TNF-αin AGA model rats were detected by ELISA.The pathological changes,the number and activation of synovial mast cells,the number of SP positive nerve fibers and the expressions of TLR2,TLR4 and MyD88 molecules were detected by HE staining and immunohistochemistry.Results:Each dose group of female red radish could reduce the levels of IL-1βand TNF-αin AGA model rats according to the dose change(P<0.01).The number of mast cells in synovium,the number of activated mast cells and the percentage of degranulation in AGA model rats could be reduced correspondingly in each dose group of female red radish(P<0.01).The distribution density of SP positive nerve fibers in the synovium of AGA model rats could be reduced correspondingly in each dose group of female red radish(P<0.01).The expressions of TLR2,TLR4 and MyD88 molecules in articular synovium of AGA model rats could be reduced correspondingly in each dose group of female radish(P<0.01).Conclusion:Female red radish can reduce the inflammatory reaction of ankle joint in AGA model rats.The activation of mast cells and SP immunoreactive nerve fibers in synovium may be involved in the inflammatory response and pain conduction of gouty arthritis.Female red radish can reduce the expression of pathway molecules TLR/MyD88/IL-1βto play its anti-inflammatory role.