基于Caspase-1/GSDMD焦亡通路探讨复方血栓通胶囊对视网膜血管炎的作用机制  

Action Mechanism of Compound Xueshuantong Capsule in Treating Retinal Vasculitis Based on Caspase-1/GSDMD Pyroptotic Signaling Pathway

作　　者：吴越[1] 张恬 李笑[1] 张秀园 刘炬[1,2] WU Yue;ZHANG Tian;LI Xiao;ZHANG Xiuyuan;LIU Ju(Shandong University of Traditional Chinese Medicine,Jinan 250013,China;Shandong Provincial Qianfoshan Hospital,Jinan 250014,China)

机构地区：[1]山东中医药大学,山东济南250013 [2]山东省千佛山医院,山东济南250014

出　　处：《中医药信息》2022年第10期7-14,共8页Information on Traditional Chinese Medicine

基　　金：山东省中医药科技发展计划项目(2019-0370)。

摘　　要：目的:基于Caspase-1/GSDMD焦亡通路探讨复方血栓通胶囊对视网膜血管炎的作用机制。方法:将60只C57BL/6小鼠随机分为空白组(Control)、模型组(Model)、复方血栓通低剂量组(FXST-L)、复方血栓通中剂量组(FXST-M)和复方血栓通高剂量组(FXST-H),每组12只。将人IRBP1-20肽溶液(100μL,5 mg/mL)与完全弗氏佐剂(100μL,含5 mg/mL结核分枝杆菌)乳化后在小鼠的头颈部、左右大腿根部及尾根部进行皮下注射,再腹腔注射百日咳毒素(100μL,5μg/mL)进行造模。造模后24 h,各组小鼠均灌胃20 d,其中Control、Model组给予蒸馏水,FXST-L、FXST-M、FXST-H组分别给予0.6、1.2、2.4 g/kg复方血栓通溶液。21 d后,各组小鼠进行视网膜眼底血管检查;HE染色法观察各组小鼠视网膜组织病理学变化;PCR法检测各组小鼠视网膜组织Caspase-1、GSDMD、IL-1βmRNA水平;Western blot法检测各组小鼠视网膜组织Caspase-1、GSDMD-N、IL-1β蛋白表达水平;ELISA法检测法小鼠血清IL-1β的表达水平。结果:与Control组比较,Model组小鼠眼底中的血管以及视网膜组织中具有明显病理变化,血管周围出现炎症浸润,视网膜组织中Caspase-1、GSDMD、IL-1βmRNA和Caspase-1、GSDMD-N、IL-1β蛋白表达水平、血清IL-1β含量均显著增高(P<0.01);与Model组比较,FXST-H组小鼠眼底中的血管以及视网膜组织中的病理变化明显缓解,血管周围炎症浸润减轻,视网膜组织中Caspase-1、GSDMD、IL-1βmRNA和Caspase-1、GSDMD-N、IL-1β蛋白表达水平、血清IL-1β含量均明显降低(P<0.01)。结论:复方血栓通胶囊可改善小鼠视网膜血管炎的病理变化及其炎性表达,其机制可能与Caspase-1/GSDMD焦亡通路有关。Objective:To explore the mechanism of Compound Xueshuantong Capsule in treating retinal vasculitis based on Caspase-1/GSDMD pyroptotic signaling pathway.Methods:60 C57BL/6 mice were randomly divided into the blank control group,the model group,the low-dose Compound Xueshuantong Capsule(FXST-L)group,the medium-dose Compound Xueshuantong Capsule(FXST-M)group and the high-dose Compound Xueshuantong Capsule(FXST-H)group,with 12 mice per group.Human IRBP1-20(100μL,5 mg/mL)was emulsified with Complete Freund's adjuvant(100μL,containing 5 mg/mL Mycobacterium tuberculosis)and injected subcutaneously into the neck,the right and left base of the thighs and the tail root in the mice,followed by intraperitoneal injection of Pertussis Toxin(100μL,5μg/mL)for modeling.24 h after modeling,the mice in each group were intervened by intragastric administration.The blank control group and the model group were given distill water,and the medication groups were given Compound Xueshuantong Capsule at the doses of 0.6 g/kg,1.2 g/kg and 2.4 g/kg.After 21 days of intervention,retinal fundus angiography was carried out in the mice of each group.The retinal histopathological changes were observed by HE staining;mRNA and protein expressions of Caspase-1,GSDMD and IL-1βwere measured by PCR and Western blot.The serum level of IL-1βwas measured by ELISA.Results:Compared with those in the blank control group,significant pathological changes in fundus blood vessels and retinal tissues could be seen in the model group;there was inflammatory infiltration around the blood vessel;the mRNA and protein expressions of Caspase-1,GSDMD and IL-1βin the retinal tissues,as well as the serum level of IL-1βwere significantly increased in the model group(P<0.01).Compared with those in the model group,the pathological changes in fundus blood vessels and retinal tissues were significantly relieved;the inflammatory infiltration around the blood vessel was reduced;the mRNA and protein expressions of Caspase-1,GSDMD and IL-1βin the retinal tissues,as well a

关 键 词：复方血栓通胶囊 视网膜血管炎 CASPASE-1 GSDMD 细胞焦亡 

分 类 号：R285.5[医药卫生—中药学]