Zhang Xianzhen, Ding Huideng, Hu Gang, Lu Ying
Department of Rheumatology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China.
Mol Med Rep. 2021 Mar;23(3). doi: 10.3892/mmr.2021.11862. Epub 2021 Jan 24.
Previous studies have suggested that the herbal medicine simiaosan has beneficial effects on gouty arthritis (GA), for which conventional Western medicines are insufficient (particularly in cases of multiple episodes). The objective of the present study was to investigate the mechanism by which simiaosan alleviated the symptoms of GA. Sprague‑Dawley rat models of acute GA were successfully established, as verified by pathological analyses. Additionally, an NLR family pyrin domain containing 3 (NLRP3) overexpression vector was constructed and a high transfection efficiency was confirmed by reverse transcription PCR. The following five treatment groups were established: i) Normal control; ii) model + saline; iii) model + simiaosan; iv) model + NALP3‑overexpressing adenovirus + simiaosan; and v) model + empty vector adenovirus + simiaosan. The samples from mice in each group were subjected to hematoxylin and eosin (H&E) staining for assessing the histopathological changes, enzyme‑linked immunosorbent assays for determining IL‑1β and TGF‑β1 levels and western blotting for evaluating NALP3 expression. H&E staining indicated that simiaosan could reduce the infiltration of inflammatory cells, while NALP3 overexpression aggravated the inflammatory response in tissues. Expression levels of IL‑1β, TGF‑β1 and NALP3 were significantly higher in the model and the model + NALP3‑overexpressing adenovirus + simiaosan groups compared with the normal control group. Levels of IL‑1β, TGF‑β1 and NALP3 were significantly lower in the model + simiaosan and model + empty vector adenovirus + simiaosan groups compared with the model group. These results indicated that the effects of simiaosan were mediated through NALP3 inhibition. Therefore, the herbal medicine simiaosan was revealed to possess an ability to alleviate the symptoms of GA by regulating the NALP3/IL‑1β signaling pathway.
先前的研究表明,中药四妙散对痛风性关节炎(GA)具有有益作用,而传统西药对此疗效欠佳(尤其是在多次发作的情况下)。本研究的目的是探究四妙散缓解GA症状的机制。通过病理分析验证,成功建立了急性GA的Sprague-Dawley大鼠模型。此外,构建了含NLR家族pyrin结构域3(NLRP3)的过表达载体,并通过逆转录PCR确认了高转染效率。设立了以下五个治疗组:i)正常对照组;ii)模型+生理盐水组;iii)模型+四妙散组;iv)模型+过表达NALP3的腺病毒+四妙散组;v)模型+空载体腺病毒+四妙散组。对每组小鼠的样本进行苏木精-伊红(H&E)染色以评估组织病理学变化,进行酶联免疫吸附测定以测定IL-1β和TGF-β1水平,并进行蛋白质印迹法以评估NALP3表达。H&E染色表明,四妙散可减少炎性细胞浸润,而NALP3过表达加剧了组织中的炎症反应。与正常对照组相比,模型组以及模型+过表达NALP3的腺病毒+四妙散组中IL-1β、TGF-β1和NALP3的表达水平显著更高。与模型组相比,模型+四妙散组和模型+空载体腺病毒+四妙散组中IL-1β、TGF-β1和NALP3的水平显著更低。这些结果表明,四妙散的作用是通过抑制NALP3介导的。因此,揭示了中药四妙散具有通过调节NALP3/IL-1β信号通路来缓解GA症状的能力。