通管方对输卵管炎性不孕模型大鼠NLRP3/Caspase-1细胞焦亡通路的影响  

Effect of Tongguan Fang(通管方)on the Pyroptosis Pathway of NLRP3/Caspase-1 Cells in Rat Model of Tubal Inflammatory Infertility

作　　者：刘梅 谢星 匡继林 LIU Mei;XIE Xing;KUANG Jilin(Hunan University of Chinese Medicine,Changsha Hunan 410208,China;Hunan Provincial Hospital of Traditional Chinese Medicine,Changsha Hunan 410005,China)

机构地区：[1]湖南中医药大学,湖南长沙410208 [2]湖南省中医院,湖南长沙410005

出　　处：《中医药导报》2023年第2期8-13,共6页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：湖南省中医药科研计划重点项目(202012)。

摘　　要：目的:探讨通管方对NLRP3/Caspase-1细胞焦亡通路的影响,为其治疗输卵管炎性不孕(SI)提供实验依据。方法:诱发SD雌性大鼠动情后,将含混合菌液的明胶海绵塞入大鼠子宫深处制备SI模型。100只大鼠随机分为通管方低剂量组、通管方中剂量组、通管方高剂量组、妇炎康胶囊组、空白组、假手术组和模型组。各药物组大鼠灌胃给予相应药物30 d后,肉眼观察输卵管外观形态及其与周围组织关系;HE染色评估输卵管病理学改变;ELISA检测血清IL-1β、IL-18水平;Western blotting检测输卵管NLRP3、Caspase-1、IL-1β、IL-18蛋白表达。结果:(1)肉眼观察可见模型组大鼠输卵管僵硬、扭曲,甚者折叠,有积脓、积液等,符合SI改变。空白组大鼠输卵管无异常改变,富有弹性。HE染色显示模型组大鼠输卵管管腔缩窄,管壁内凹增厚,纤毛减少、断裂,见大量炎症细胞浸润;空白组大鼠输卵管管壁光滑,细胞排列整齐,纤毛完整、数量众多,无炎症细胞浸润。模型组与空白组差异明显,说明造模基本成功。通管方灌胃后,输卵管纤毛数量增多,纤毛结构恢复,炎症细胞浸润减少。(2)通管方中、高剂量组可显著降低模型大鼠血清IL-1β、IL-18水平(P<0.05)。(3)通管方中、高剂量组可下调SI大鼠输卵管NLRP3、Caspase-1、IL-1β和IL-18蛋白相对表达量,与模型组比较,差异均有统计学意义(P<0.05)。结论:(1)诱发大鼠动情经阴道接种混合菌液法可成功制造SI模型,且致病机制与临床相近,值得推广。(2)通管方可减轻模型大鼠炎症反应,改善输卵管黏膜充血水肿,促进积水、积脓及系膜包裹性积液的吸收,改善输卵管外观形态,松解盆腔粘连,促进纤毛再生及功能恢复。(3)通管方可降低SI模型大鼠NLRP3、Caspase-1、IL-1β、IL-18等因子的表达,其机制可能与抑制NLRP3/Caspase-1细胞焦亡通路活化相关。Objective:To explore the effect of Tongguan Fang on the pyroptosis pathway of NLRP3/Caspase-1 cells,and provide experimental basis for its treatment of salpingitis infertility(SI).Methods:After inducing estrus in SD female rats,gelatin sponge containing mixed bacterial fluid was inserted into the deep uterus of rats to prepare SI model.100 rats were randomly divided into low,medium and high dose groups of Tongguan Fang,Fuyankang Capsules(妇炎康胶囊)group,blank group,sham operation group and model group.After intragastric administration of corresponding drugs to rats in each group for 30 days,the appearance of fallopian tubes and their relationship with surrounding tissues were observed by visual observation.The pathological changes of fallopian tubes were evaluated by HE staining.The levels of serum IL-1βand IL-18 were detected by ELISA.Western blotting was used to detect the expression of NLRP3,Caspase-1,IL-1βand IL-18 protein in fallopian tubes.Results:(1)The visual observation showed that the fallopian tube of rats in the model group were stiff,twisted,even folded,with pus and fluid accumulation,which were consistent with the SI change.The fallopian tubes of rats in the blank group had no abnormal changes and were elastic.HE staining showed that the tubal lumen of rats in the model group were narrowed,the inner concave of the tubal wall were thickened,the cilia were reduced and broken,and a large number of inflammatory cells were infiltrated.In the blank group,the fallopian tube wall were smooth,the cells were orderly arranged,the cilia were complete and numerous,and there were no inflammatory cell infiltration.The difference between the model group and the blank group was obvious,which indicated that the modeling was basically successful.After intragastric administration of Tongguan Fang,the number of cilia in the fallopian tube increased,the cilia structure recovered,and the infiltration of inflammatory cells decreased.(2)The middle and high dose groups of Tongguan Fang could significantly reduce the

关 键 词：输卵管炎性不孕 通管方 细胞焦亡 NLRP3 CASPASE-1 大鼠 

分 类 号：R285.5[医药卫生—中药学]