摘要
目的 探究黄芩汤调控miR-143/TLR2/NF-κB/NLRP3通路对湿热型溃疡性结肠炎大鼠细胞焦亡的影响。方法 采用“DSS+复合因素”对大鼠进行溃疡性结肠炎湿热证模型的构建,实验分为正常组、模型组、黄芩汤低剂量组、黄芩汤中剂量组、黄芩汤高剂量组。HE染色观察病理学改变,ELISA检测血清IL-1β和IL-18因子表达,Western blot检测TLR2、NF-κB(p-p65)、GSDMD蛋白表达水平,qPCR检测结肠组织miR-143、TLR2、NLRP3、NF-κB、Caspase-1和GSDMD mRNA水平。结果 与正常组相比,模型组结肠病理组织有所损伤,IL-1β、IL-18炎症因子水平及TLR2、p-p65、GSDMD蛋白表达量显著升高,NLRP3、GSDMD、TLR2、NF-κB、caspase-1 mRNA水平明显升高,miR-143明显降低;与模型相比,中高剂量黄芩汤组结肠病理组织损伤有所改善,其中低剂量组血清IL-1β水平、中高剂量组血清中IL-1β和IL-18水平明显降低。低剂量组p-p65蛋白表达量明显降低,中高剂量组TLR2、p-p65和GSDMD蛋白表达量明显下降。低剂量组NF-κB和NLRP3 mRNA表达量明显降低;中剂量组TLR2、NF-κB、caspase-1、GSDMD mRNA明显降低;高剂量组miR-143显著升高,TLR2、NF-κB、GSDMD、NLRP3 mRNA显著降低。结论 黄芩汤可能是通过调控miR-143/TLR2/NF-κB/NLRP3通路抑制湿热型溃疡性结肠炎大鼠细胞焦亡,从而发挥对湿热型UC作用。
Objective To explore the regulation of miR-143/TLR2/NF-kB/NLRP3 pathway by Huangqin Decoction on damp-heat ulcerative colitis rats.Methods The damp-heat model of ulcerative colitis was established by DSS+complex factors.The experiment was divided into normal group,model group,low-dose Huangqin Decoction group,medium-dose Huangqin de-coction group and high-dose Huangqin decoction group.The pathological changes were observed by HE staining,the expression of serum IL-1βand IL-18 factor was detected by ELISA,and the expression levels of TLR2,NF-kB(p-p65)and GSDMD protein were detected by Western blot.mRNA levels of miR-143,TLR2,NLRP3,NF-kB,Caspase-1 and CSDMD in colon tissues were detected by qPCR.Results Compared with the normal group,the pathological tissue of colon in the model group was damaged,the levels of IL-1β,IL-18 inflammatory factors,the protein expressions of TLR2,p-p65 and GSDMD were signifi-cantly increased,and the mRNA levels of NLRP3,GSDMD,TLR2,NF-kB and caspase-1 were significantly increased.miR-143 decreased significantly.Compared with the model,the colonic pathological tissue damage was improved in the medium and high dose Huangqin Decoction group,and the serum IL-1βand IL-18 levels in the low dose group and the medium and high dose group were significantly reduced.The expression of p-p65 protein decreased significantly in low-dose group,and the ex-pression of TLR2,P-p65 and GSDMD protein decreased significantly in medium-high dose group.The mRNA expressions of NF-kB and NLRP3 were significantly decreased in the low-dose group.The mRNA levels of TLR2,NF-kB,caspase-1 and GSDMD were significantly decreased in the medium dose group.In high-dose group,miR-143 was significantly increased,and TLR2,NF-kB,GSDMD,NLRP3 mRNA were significantly decreased.Conclusion Huangqin Decoction may inhibit pyroptosis in rats with damp-heat ulcerative colitis by regulating miR-143/TLR2/NF-kB/NLRP3 pathway,so as to play a role on damp-heat UC.
作者
朱璠
曾娟
蒋南飞
黄浪浪
吴娜
ZHU Fan;ZENG Juan;JIANG Nan-fei;HUANG Lang-lang;WU Na(Jiangxi University of Chinese Medicine,Nanchang Jiangxi 330004,China;Afiliated Hospital of Jiangxi University of Chinese Medicine,Nanchang Jiangxi 330006,China)
出处
《时珍国医国药》
CAS
CSCD
北大核心
2024年第8期1872-1876,共5页
Lishizhen Medicine and Materia Medica Research
基金
江西省自然科学基金青年基金(20212BAB216060)
江西省中医药中青年骨干人才(第四批)培养计划(赣中医药科教字[2022]7号)
国家自然科学基金(82160903)。
