可善挺通过抑制C5a/C5aR1通路对银屑病小鼠皮肤炎症和自噬的调控作用  

Cosentyx regulates skin inflammation and autophagy in psoriasis mice through the C5a/C5aR1 signaling pathway

作　　者：杨羽[1] 赵菊花[1] 黎官印[1] 李达[1] 王洁[1] 陈颖 李燃[1] YANG Yu;ZHAO Juhua;LI Guanyin;LI Da;WANG Jie;CHEN Ying;LI Ran(Nanchong Central Hospital,the Second Clinical Medical College of North Sichuan Medical College,Nanchong 637000,China)

机构地区：[1]川北医学院第二临床医学院·南充市中心医院,四川南充637000

出　　处：《中国比较医学杂志》2021年第8期21-28,共8页Chinese Journal of Comparative Medicine

基　　金：四川省卫生和计划生育委员会科研课题(18PJ421)。

摘　　要：目的本研究拟通过咪喹莫特(IMQ)小鼠银屑病模型,探究可善挺(Cosentyx)通过C5a/C5aR1通路对银屑病小鼠皮肤炎症和自噬的调控作用。方法 8周龄雄性BALB/c小鼠27只,随机分成3组(每组9只):空白对照组(Blank group)、银屑病模型组(Model group)、可善挺治疗组(Cosentyx-treat group),除空白对照组外,其余两组采用咪喹莫特(IMQ)制备银屑病模型,可善挺治疗组给与可善挺(第1、6、13天皮下注射,1 d两次,每次4.5mg/kg)干预。通过HE染色观察可善挺对银屑病模型小鼠皮肤组织的病理损伤的影响,通过ELISA检测小鼠皮损组织中促炎因子IL-4、IL-8、TNF-α、IL-1β的分泌情况,通过分光光度法检测小鼠皮损组织中髓过氧化物酶(MPO)活性,通过Western blot检测小鼠皮损组织中Beclin 1的表达量和LC3-Ⅱ/LC3-Ⅰ值,通过免疫组化法检测小鼠皮损组织C5a、C3、C5aR1、C1qB的表达水平。结果可善挺抑制了皮损组织中IL-4、IL-8、TNF-α、IL-1β和MPO的表达,提高了Beclin 1的表达和LC3-Ⅱ/LC3-Ⅰ比值,同时可善挺下调了C5a/C5aR1通路中C1qB、C3、C5a、C5aR1分子的表达。结论可善挺抑制了C5a/C5aR1通路,可以通过C5a/C5aR1通路调控银屑病皮损组织中炎症因子的表达,减缓银屑病炎症反应,同时可善挺增强了银屑病皮损组织中自噬作用,但无法确定可善挺是否通过C5a/C5aR1通路对银屑病皮损组织中自噬作用进行调控,因此机制还需进一步确定。Objective To explore the regulatory effect of Cosentyx on skin inflammation and autophagy in psoriasis mice( IMQ-induced) through the C5a/C5aR1 pathway. Methods Twenty-eight 8-week-old BALB/c male mice were assigned to three groups of nine mice each: Blank,Psoriasis-Model,and Cosentyx-Treated Groups. All except the Blank Group received IMQ and the Cosentyx-Treated Group was treated with Cosentyx( subcutaneous injection,4. 5 mg/kg twice a day on days 1,6,and 13). HE staining was used to observe the effect of Cosentyx on pathological damage in the skin of psoriasis mice. ELISA was used to measure the secretion of the proinflammatory cytokines IL-4,IL-8,TNF-α,and IL-1β in psoriasis mouse skin. Spectrophotometry was used to observe the activity of medullary peroxidase( MPO) in mouse skin. Western blot analyses were used to measure Beclin 1 expression and LC3-Ⅱ/LC3-Ⅰ values. Immunohistochemistry analyses were performed to detect the expressions of C5a,C3,C5aR1,and C1 qB in skin. Results Cosentyx inhibited the expressions of IL-4,IL-8,TNF-α,IL-1β,and MPO in dermal tissues,improved Beclin 1 expression and the LC3-Ⅱ/LC3-Ⅰ ratio,and downregulated the expressions of C1 qB,C3,C5a,and C5aR1. Conclusions Cosentyx inhibited the C5a/C5aR1 pathway,regulated the expression of inflammatory cytokines in psoriasis skin,and slowed psoriasis inflammation.Cosentyx enhanced autophagy in psoriasis skin tissues but we did not determine whether Cosentyx controlled autophagy through the C5a/C5aR1 pathway. Therefore,the mechanism requires further study.

关 键 词：银屑病炎症 可善挺 C5a/C5aR1通路 自噬 

分 类 号：R-33[医药卫生]