穿心莲内酯调节NLRP3/caspase-1信号通路对银屑病大鼠皮肤损伤的影响  

Effect of andrographolide on skin damage in psoriatic rats by regulating the NLRP3/caspase⁃1 signaling pathway

作　　者：张倩 贺晋栋 ZHANG Qian;HE Jin-dong(Department of Dermatology,Second Peoples Hospital of Jincheng City,Jincheng,Shanxi Province 048006,China;Health Management Center,Second Peoples Hospital of Jincheng City,Jincheng,Shanxi Province 048006,China)

机构地区：[1]山西省晋城市第二人民医院皮肤科,山西晋城048006 [2]山西省晋城市第二人民医院健康管理中心,山西晋城048006

出　　处：《解剖学研究》2025年第1期25-31,共7页Anatomy Research

基　　金：山西省卫生健康委科研课题(2018139)。

摘　　要：目的探讨穿心莲内酯调节Nod样受体蛋白3(NLRP3)/胱天蛋白酶-1(caspase-1)通路对银屑病大鼠皮肤损伤的影响。方法72只SPF级雄性SD大鼠随机分为对照组、银屑病组、穿心莲内酯组、甲氨蝶呤组、二乙基二硫代氨基甲酸酯(DDC)组、穿心莲内酯+DDC组,每组12只。除对照组外,其它组大鼠需构建银屑病模型,建模成功24 h后,进行处理,每日处理1次,连续处理30 d。评估严重程度指数(PASI)评分的变化;HE染色检测大鼠皮肤组织病理学变化;免疫组化染色检测大鼠皮肤组织中分化簇3(CD3)、抗原Ki67(Ki67)表达;ELISA检测大鼠皮肤组织中IL-6、IL-17A、TNF-α含量;Western blot检测大鼠皮肤组织中NLRP3、剪切的caspase-1(cleaved-caspase-1)、IL-1β蛋白表达。结果与对照组比较,银屑病组大鼠皮肤结构紊乱,表皮可见明显角化过度,真皮层内有大量炎性细胞浸润,PASI评分、CD3、Ki67阳性细胞数、IL-6、IL-17A、TNF-α含量及NLRP3、cleaved-caspase-1、IL-1β蛋白表达升高(P<0.05);与银屑病组比较,穿心莲内酯组、甲氨蝶呤组大鼠表皮角化及真皮层内炎性细胞浸润程度有所改善,PASI评分、CD3、Ki67阳性细胞数、IL-6、IL-17A、TNF-α含量及NLRP3、cleaved-caspase-1、IL-1β蛋白表达降低,而DDC组对应指标变化趋势与上述相反(P<0.05);与穿心莲内酯组比较,穿心莲内酯+DDC组大鼠皮肤组织病理损伤严重,PASI评分、CD3、Ki67阳性细胞数、IL-6、IL-17A、TNF-α含量及NLRP3、cleaved-caspase-1、IL-1β蛋白表达升高(P<0.05)。结论穿心莲内酯可能通过抑制NLRP3/caspase-1通路改善银屑病大鼠皮肤损伤。Objective To investigate the effect of andrographolide on skin damage in psoriasis rats by regu⁃lating Nod⁃like receptor protein 3(NLRP3)/cysteinyl aspartate specific protease⁃1 pathway.Methods Seventy⁃two SD rats were divided randomly into control group,psoriasis group,andrographolide group,methotrexate group,DDC group,and andrographolide+DDC group,with 12 rats in each group.Except for the control group,rats in oth⁃er groups were used to construct psoriasis models.After successful modeling for 24 hours,they were treated once a day for 30 consecutive days.The changes in the severity index(PASI)score were evaluated;HE staining was ap⁃plied to detect pathological changes in skin tissue;immunohistochemical staining was applied to detect the expres⁃sion of CD3 and antigen Ki67(Ki67)in skin tissue;ELISA was applied to detect the levels of IL⁃6,IL⁃17A,and TNF⁃αin skin tissue;Western blot was applied to detect the expression of NLRP3,cleaved⁃caspase⁃1,and IL⁃1βproteins in skin tissue.Results Compared with the control group,the skin structure of rats in the psoriasis group was disordered,with obvious hyperkeratosis in the epidermis and a large number of inflammatory cells infiltrating the dermis,the PASI score,the counts of CD3 and Ki67 positive cells,contents of IL⁃6,IL⁃17A,TNF⁃α,and the ex⁃pression of NLRP3,cleaved⁃caspase⁃1,and IL⁃1βproteins increased(P<0.05);compared with the psoriasis group,the epidermal keratinization and inflammatory cell infiltration in the dermis of rats in andrographolide group and methotrexate group improved,the PASI score,the counts of CD3 and Ki67 positive cells,contents of IL⁃6,IL⁃17A,TNF⁃α,and the expression of NLRP3,cleaved⁃caspase⁃1,and IL⁃1βproteins decreased,the change trend of corresponding indicators in the DDC group was opposite to the above(P<0.05);compared with the an⁃drographolide group,the skin tissue pathological damage of rats in andrographolide+DDC group was severe,the PASI score,the counts of CD3 and Ki67 positive c

关 键 词：银屑病 穿心莲内酯 Nod样受体蛋白3/胱天蛋白酶-1通路 皮肤损伤 炎症 

分 类 号：R285.5[医药卫生—中药学]