荭草苷通过PPAR-γ/LXR-α/ABCG1信号通路改善MSU晶体诱导的大鼠急性关节炎  

Orientin alleviates joint inflammation in MSU crystals-induced acute gouty arthritis rats by regulating PPAR-γ/LXR-α/ABCG1 pathway

作　　者：徐鑫淼 沈磊 柳林 滕雅芹 原平玫 XU Xinmiao;SHEN Lei;LIU Lin;TENG Yaqin;YUAN Pingmei(Department of Endocrinology,Yantai Yeda Hospital,Yantai 264100,China;Imaging Department of Yantai Yeda Hospital,Yantai 264100,China;Department of Endocrinology,Yantai Affiliated Hospital of Binzhou Medical College,Yantai 264100,China;Laboratory Department of Yantai Yeda Hospital,Yantai 264100,China)

机构地区：[1]烟台业达医院内分泌科,264100 [2]烟台业达医院影像科,264100 [3]烟台业达医院检验科,264100 [4]滨州医学院烟台附属医院内分泌科,264100

出　　处：《免疫学杂志》2022年第10期876-882,共7页Immunological Journal

基　　金：烟台市科技计划(2021YD100,2022YD082)。

摘　　要：目的基于过氧化物酶体增殖物激活受体-γ(PPAR-γ)/肝X受体-α(LXR-α)/ATP结合盒转运体G1(ABCG1)信号通路明确荭草苷改善MSU晶体诱导的大鼠急性关节炎的作用。方法SD大鼠随机分为对照组、急性关节炎模型组、荭草苷组、GW9662(PPAR-γ抑制剂)组、荭草苷+GW9662组,每组12只。模型组和给药组以踝关节注射单钠尿酸盐(MSU)晶体的方法诱导大鼠急性关节炎模型。给药组给予荭草苷或/和GW9662干预,1次/d,共14 d。对大鼠步态进行评分;评测大鼠左踝关节炎症指数及左踝关节横截面周长;酶联免疫试剂盒检测大鼠左踝关节滑膜组织和血清炎性因子IL-6、IL-18水平;HE染色观察大鼠左踝关节滑膜组织病理形态;免疫印迹检测大鼠左踝关节滑膜组织PPAR-γ/LXR-α/ABCG1通路蛋白表达。结果与对照组相比,模型组大鼠步态评分、炎症指数、左踝关节横截面周长、IL-6及IL-18水平明显升高(P<0.05);关节滑膜组织肌纤维坏死、核破裂,结缔组织明显增生,伴有大量中性粒细胞、巨噬细胞及淋巴细胞等炎性细胞浸润;关节滑膜组织PPAR-γ、LXR-α、ABCG1蛋白表达明显降低(P<0.05)。与模型组、荭草苷+GW9662组分别相比,荭草苷组大鼠步态评分、炎症指数、左踝关节横截面周长、IL-6及IL-18水平降低(P<0.05),关节滑膜组织病理损伤明显减轻,关节滑膜组织PPAR-γ、LXR-α、ABCG1蛋白表达升高(P<0.05);GW9662组大鼠步态评分、炎症指数、左踝关节横截面周长、IL-6及IL-18水平升高(P<0.05),关节滑膜组织病理损伤明显加重,关节滑膜组织PPAR-γ、LXR-α、ABCG1蛋白表达降低(P<0.05)。结论荭草苷可通过激活PPAR-γ/LXR-α/ABCG1通路,抑制MSU晶体诱导的大鼠急性关节炎症,减轻关节滑膜组织损伤,改善关节功能。This study was performed to explore the effect of orientin on joint inflammation in rats with acute gouty arthritis(AGA)by regulating the peroxisome proliferator-activated receptor-γ(PPAR-γ)/liver X receptor-α(LXR-α)/ATP-binding cassette transporter G1(ABCG1)pathway.SD rats were randomly divided into control group,model group,orientin group,GW9662(PPAR-γinhibitor)group,orientin+GW9662 group,with 12 rats in each group.AGA rat model was induced by injecting monosodium urate(MSU)crystal suspension into ankle joint.The intervention of orientin or/and GW9662 was carried out once a day for 14 days.The gait of the rats was observed and scored;the inflammation index and the cross-sectional circumference of the left ankle joint were evaluated;the pathological morphology of the synovial tissue wasobserved with HE staining;the levels of IL-6 and IL-18in the synovial tissue and serum were detected with theELISA kits;the expression of PPAR-γ/LXR-α/ABCG1pathway proteins in the synovial tissue were detected with Western blotting.Compared with the control group,the synovial tissue of the model group rats demonstratednecrosis of muscle fibers,rupture of the nucleus,and obvious hyperplasia of connective tissue,accompanied by alarge number of neutrophils,macrophages,lymphocytes and other inflammatory cells infiltration,showing significantpathological changes,and the gait score,inflammation index,left ankle joint cross-sectional circumference,IL-6 andIL-18 levels were significantly increased(P<0.05),while the expression of PPAR-γ,LXR-αand ABCG1 proteins injoint synovial tissue were significantly reduced(P<0.05).Compared with the model group and the orientin+GW9662group,the gait score,inflammation index,left ankle joint cross-sectional circumference,IL-6 and IL-18 levels in theorientin group were reduced(P<0.05),the pathological damage of the synovial tissue was significantly reduced,thePPAR-γ,LXR-αand ABCG1 protein expression in joint synovial tissue were increased(P<0.05).Furthermore,thegait score,inflammation index,left

关 键 词：荭草苷 急性痛风性关节炎 过氧化物酶体增殖物激活受体-γ/肝X受体-α/ATP结合盒转运体G1通路 作用机制 

分 类 号：R684.3[医药卫生—骨科学]