基于Treg/Th17平衡探究柚皮素改善模型大鼠类风湿关节炎的作用机制-现代医学

基于Treg/Th17平衡探究柚皮素改善模型大鼠类风湿关节炎的作用机制

单位：1. 湖北省十堰市太和医院中西医结合科, 湖北十堰 442000;
2. 十堰市人民医院中医科, 湖北十堰 442000

分类号：R593.22;R-33

出版年·卷·期（页码）：2023·51·第五期（618-624）

摘要：

目的：探究柚皮素(NAR)对模型大鼠类风湿关节炎(RA)的改善作用以及调节Treg/Th17平衡的机制。方法：将72只SPF级Wistar雄性大鼠分成对照组、模型组、阳性组(雷公藤多苷组)以及NAR低、中、高剂量组6组，每组12只。对各组大鼠进行关节病变评分；苏木素-伊红染色观察大鼠滑膜组织病理形态的变化；TUNEL法检测大鼠滑膜组织的细胞凋亡率；试剂盒检测大鼠血清中髓过氧化物酶(MPO)的活性，酶联免疫吸附检测大鼠血清中类风湿因子(RF)、C反应蛋白(CRP)、白细胞介素17(IL-17)、转化生长因子-β1(TGF-β1)、白细胞介素10(IL-10)的水平，蛋白质印迹法检测大鼠滑膜组织中视黄酸相关孤儿受体γt(ROR-γt)、叉头状转录因子(Foxp3)蛋白的表达。结果：与对照组相比，模型组大鼠滑膜组织显著增生，滑膜内血管扩张，炎症细胞浸润较多并伴随组织纤维化，关节病变评分、滑膜组织细胞凋亡率以及血清中MPO、RF、CRP、IL-17、RORγt水平升高，IL-10、TGF-β1及Foxp3表达水平降低(P＜0.05)；与模型组相比，阳性组和NAR低、中、高剂量组大鼠滑膜组织和血管增生减少，炎症细胞浸润减少，组织纤维化不明显，关节病变评分、滑膜组织细胞凋亡率以及血清中MPO、RF、CRP、IL-17、RORγt水平降低，IL-10、TGF-β1及Foxp3表达水平升高(P＜0.05)。结论：NAR能够通过调节Treg/Th17平衡对大鼠RA起到改善作用。

Objective: To investigate the effect of Naringenin(NAR) on improving rheumatoid arthritis(RA) in model rat and its mechanism in regulating Treg/Th17 balance. Methods: Seventy-two SPF Wistar male rats were divided into control group, model group, positive group(Tripterygium wilfordii polyglycoside group), NAR low dose group, NAR medium dose group and NAR high dose group, with 12 rats in each group. The joint lesions of rats in each group were scored; the pathological changes of rat synovium were observed by hematoxylin eosin staining, and the apoptosis rates of rat synovium were detected by TUNEL method; the activity of myeloperoxidase(MPO) in rat serum was detected by the kit, the levels of rheumatoid factor(RF), C-reactive protein(CRP), interleukin-17(IL-17), transforming growth factor-β1(TGF-β1) and interleukin-10(IL-10) in serum were determined by enzyme-linked immunosorbent assay, and the expressions of retinoic acid related orphan receptor γt(RORγt) and forkhead transcription factor 3(Foxp3) protein in rat synovium were detected by Western blot. Results: Compared with the control group, the synovial tissue in the model group was obviously hyperplastic, the blood vessels in the synovium were dilated, and inflammatory cells were infiltrated more and accompanied by tissue fibrosis. The score of joint lesions, the apoptosis rate of synovial cells, the levels of MPO, RF, CRP, IL-17 and RORγt in serum increased, and the expression levels of IL-10, TGF-β1 and Foxp3 decreased(P＜0.05). Compared with the model group, the synovial tissue and vascular proliferation of rats in the positive group and NAR low, medium and high dose groups decreased, the inflammatory cell infiltration was reduced, and the tissue fibrosis was not obvious. The score of joint lesions, the apoptosis rate of synovial cells, the levels of MPO, RF, CRP, IL-17 and RORγt in serum decreased, and the expression levels of IL-10, TGF-β1 and Foxp3 increased(P＜0.05). Conclusion: NAR can improve RA rats by regulating Treg/Th17 balance.

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