摘要
目的:从抑制细胞焦亡的角度探索膈下逐瘀汤加减方治疗慢性输卵管炎(CS)的作用机制.方法:50只雌性SD大鼠随机分为空白组,模型组,膈下逐瘀汤加减方低、中、高剂量组.膈下逐瘀汤加减方低、中、高剂量组分别给予0.9、1.8、3.6g/kg膈下逐瘀汤加减方灌胃,空白组、模型组给予等体积纯净水.HE染色观察输卵管病理,qRT-PCR检测组织lncT048561、lncENST00000602957及NLRP3、caspase-1、GSDMD、IL-18、IL-1β mRNA表达.Western Blot检测NLRP3、procaspase-1、cleaved caspase-1、GSDMD-N蛋白表达.ELISA检测血清IL-18、IL-1β表达.结果:与空白组比较,模型组输卵管炎性损伤明显,lncT048561、lncENST0000060295、NLRP3、caspase-1、GSDMD、IL-18、IL-1 β mRNA增高,NLRP3、cleaved caspase-1、GSDMD-N蛋白和血清IL-18、IL-1β增高(P<0.05).与模型组比较,除GSDMDmRNA、NLRP3蛋白在膈下逐瘀汤加减方低剂量组变化不明显外,膈下逐瘀汤加减方各剂量组以上指标均能改善(P<0.05,P<0.01).结论:膈下逐瘀汤加减方能够抑制lncRNAs/NLRP3炎症小体通路介导的细胞焦亡治疗CS.
Abstract
Objective:To explore the therapeutic mechanism of modified Gexiazhuyu Decoction(GXZYD)on chronic salpingitis(CS)from the perspective of inhibiting pyroptosis.Methods:Fifty female SD rats were randomly divided into the control group,model group,GXZYD-low,-medium and-high dose groups.GXZYD-low,-medium and-high dose groups were gavaged with 0.9,1.8,3.6 g/kg of GXZYD,control group and model group were gavaged with equal volume purified water.HE staining was used to assess tubal pathology,qRT-PCR was used to detect tubal lncT048561,lncENST00000602957,and mRNAs levels of NLRP3,caspase-1,GSDMD,IL-18 and IL-1 β.Western Blot was used to detect tubal NLRP3,procaspase-1,cleaved caspase-1 and GSDMD-N proteins,and ELISA was used to test serum IL-18 and IL-1 β expressions.Results:Compared with the control group,tubal inflammatory injury was obvious in the model group,and lncT048561,lncENST0000060295,and mRNAs of NLRP3,caspase-1,GSDMD,IL-18 and IL-1 β were all increased(P<0.05).The protein levels of NLRP3,cleaved caspase-1,GSDMD-N,and serum IL-18 and IL-1β were all increased(P<0.05).Compared with the model group,GXZYD each dose groups improved these indexes(P<0.05,P<0.01),with the exception of GSDMD mRNA and NLRP3 protein remained unchanged in the GXZYD-low dose group.Conclusion:GXZYD inhibits lncRNAs/NLRP3 inflammasome mediated pyroptosis and alleviate CS.
基金项目
黑龙江省自然科学基金面上项目(H2015026)
中央支持地方高校改革发展资金人才培养项目(2021ZYGLG001)