NALP6信号转导通路在痛风性关节炎发病过程中的作用机制

Study on the Mechanism of NALP6 Signal Transduction Pathway in the Pathogenesis of Gout Arthritis

目的:探讨NALP6信号转导通路在痛风性关节炎(GA)发病过程中的作用机制。方法:选取慢病毒转染技术干扰NALP6蛋白的基因表达,采用酶联免疫吸附试验(ELISA)、蛋白质印迹法(Western blotting)、逆转录聚合酶链反应(RTPCR)等技术检测细胞中NALP6蛋白、caspase-1、IL-1β、核因子-κB的表达情况;结果:干扰成纤维滑膜细胞中NALP6基因的表达,能减低痛风性关节炎成纤维样滑膜细胞中NALP6蛋白的表达、降低caspase-1和核因子-κB的活性,降低IL-1β含量;结论:NALP6炎性反应信号转导通路参与了大鼠痛风性关节炎的发病过程,通过能够干扰NALP6基因表达的慢病毒转染技术能保护痛风性关节炎成纤维样滑膜细胞的炎性损伤。

Objective: To investigate the action mechanism of the NALP6 signal transduction pathway involved in gout arthritis(GA). Methods: The lentiviral transfection technology was used to interfere the expression of NALP6 gene and the expression of NALP6,caspase-1,IL-1β and NF-κB was detected by using Elisa,Western Blot and RT-PCR technology. Results: Interfering the expression of the NALP6 genes could reduce the expression levels of NALP6 protein and RNA and NF-κB protein,the activity of caspase-1 and the content of IL-1β in fibroblast-like synoviocytes. Conclusion: 1)The study confirmed that the NALP6 signal transduction pathway is involved in the pathogenesis process of GA in rats and revealed that the inflammatory signal of “NALP6-caspase-1-IL-1β” and the cycle pathway of inflammatory cascade between IL-1β and NF-κB play an important role in the process of gouty arthritis.2)The method of interfering the genes expression of NALP6 by lentiviral transfection technology can protect the inflammation injury of fibroblast-like synoviocytes.3)Regarding NALP6 as a target may provide a new idea for clinical prevention and treatment of gouty arthritis.