青藤碱对FLS增殖及α7nAChR、TLR2和TLR4表达的影响

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目的探讨青藤碱(sinomenine,SIN)对肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)刺激的大鼠成纤维样滑膜细胞(fibroblast-like synoviocytes,FLS)增殖及α7烟碱型乙酰胆碱受体(α7 nicotinic acetylcholine receptors,α7n ACh R)、Toll样受体2(toll-like receptor 2,TLR2)和Toll样受体4(toll-like receptor 4,TLR4)表达的影响。方法组织块法分离培养原代FLS,流式细胞术检测FLS表面标志物CD90。FLS设对照组、TNF-α组、SIN组(100,200,400μmol·L~(-1)),SIN组给予SIN干预30 min后,TNF-α组、SIN组均给予20 ng·m L~(-1)TNF-α刺激24 h,采用MTT法检测各组FLS增殖,酶联免疫吸附(ELISA)法检测细胞上清白细胞介素-6(interleukin-6,IL-6)分泌量,RT-PCR法检测α7n ACh R、TLR2和TLR4 m RNA表达及Western bolt法检测α7n ACh R、TLR2和TLR4蛋白表达。结果 TNF-α刺激FLS后,细胞明显增殖,分泌IL-6明显增加,α7n ACh R、TLR2和TLR4 m RNA及蛋白表达增加,SIN(200,400μmol·L~(-1))能抑制FLS增殖,抑制IL-6分泌,并且下调α7n ACh R、TLR2和TLR4 m RNA及蛋白表达。结论 FLS增殖与α7n ACh R、TLR2和TLR4表达相关,且SIN能抑制FLS增殖,并下调α7n ACh R、TLR2和TLR4表达。 Objective To investigate the effects of sinomenine (SIN) on the proliferation of rat fibroblast-like synoviocytes (FLS) stimulated by tumor necrosis factor-α (TNF-α) and α7 nicotine Α7n AChR, toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) were detected by Western blot. Methods Primary FLS was isolated and cultured by tissue block method, and FLS surface marker CD90 was detected by flow cytometry. In the control group, TNF-α group and SIN group (100, 200, 400μmol·L -1) 1) TNF-α stimulation for 24 h, the proliferation of FLS in each group was detected by MTT assay, and the secretion of interleukin-6 (IL-6) in the supernatant of the cells was detected by enzyme linked immunosorbent assay (ELISA) The expressions of α7n ACh R, TLR2 and TLR4 m RNA were detected by Western blot, and the expressions of α7n ACh R, TLR2 and TLR4 were detected by Western blot. Results After FLS stimulated with TNF-α, the cells were significantly proliferated, the secretion of IL-6 was significantly increased, the expressions of α7n ACh R, TLR2 and TLR4 m RNA and protein were increased. SIN (200,400μmol·L -1) inhibited FLS proliferation, Inhibit IL-6 secretion, and down-regulate α7n ACh R, TLR2 and TLR4 m RNA and protein expression. Conclusion The proliferation of FLS is related to the expression of α7n ACh R, TLR2 and TLR4, and SIN can inhibit the proliferation of FLS and down-regulate the expression of α7n ACh R, TLR2 and TLR4.
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