基于HOXA-AS3/miR-29a-3p/LTβR/NF-κB轴探讨健脾通络解毒方改善慢性萎缩性胃炎作用机制OA
Exploration on the Mechanism of Jianpi Tongluo Jiedu Prescription on Chronic Atrophic Gastritis Based on HOXA-AS3/miR-29a-3p/LTβR/NF-κB Axis
目的 基于HOXA-AS3/miR-29a-3p/LTβR/NF-κB轴探讨健脾通络解毒方干预慢性萎缩性胃炎(CAG)作用机制.方法 采用1-甲基-3-硝基-1-亚硝基胍联合雷尼替丁复合造模法诱导CAG大鼠模型.将大鼠随机分为空白组、模型组、胃复春胶囊组和健脾通络解毒方低、中、高剂量组,干预10周后,HE染色观察大鼠胃组织形态,ELISA法检测大鼠血清白细胞介素(IL)-1β、IL-18、IL-10、胃泌素(GAS)、胃动素(MTL)含量,RT-PCR和Western blot检测胃组织HOXA-AS3/miR-29a-3p/LTβR/NF-κB轴相关基因和蛋白表达.结果 与空白组比较,模型组大鼠胃黏膜腺体萎缩,大量炎性细胞浸润,血清IL-1β、IL-18、GAS含量显著升高(P<0.01),IL-10、MTL 含量显著降低(P<0.01),胃组织 HOXA-AS3、LTβR、NF-κB p65、NLRP3、IL-1β和IL-18 mRNA表达显著升高(P<0.05),miR-29a-3p表达显著降低(P<0.01),胃组织LTβR、p-IκBα、p-NF-κB p65、Caspase-1、NLRP3蛋白表达均显著升高(P<0.01);不同剂量健脾通络解毒方干预后,胃黏膜病理损伤不同程度改善,血清IL-1β、IL-18、GAS含量降低,IL-10、MTL含量升高,胃组织HOXA-AS3/miR-29a-3p/LTβR/NF-κB轴相关mRNA和蛋白表达不同程度逆转,其中健脾通络解毒方高剂量组差异均有统计学意义(P<0.05,P<0.01).结论 健脾通络解毒方能有效改善CAG大鼠胃黏膜组织病理损伤,其作用机制可能与调控HOXA-AS3/miR-29a-3p/LTβR/NF-κB轴有关.
Objective To investigate the mechanism of Jianpi Tongluo Jiedu Prescription in intervening in chronic atrophic gastritis(CAG)based on HOXA-AS3/miR-29a-3p/LTβR/NF-κB axis.Methods A CAG model was induced in rats using a compound modeling method involving 1-methyl-3-nitro-1-nitrosoguanidine combined with ranitidine.The rats were randomly divided into the following groups:blank group,model group,Weifuchun Capsule group and Jianpi Tongluo Jiedu Prescription low-,medium-,high-dosage groups.The intervention lasted for 10 weeks.Pathological changes in gastric tissue were observed via HE staining,the expression of genes and proteins related to the HOXA-AS3/miR-29a-3p/LTβR/NF-κB axis in gastric tissue were measured using RT-PCR and Western blot,respectively,serum contents of IL-1β,IL-18,IL-10,GAS and MTL were detected via ELISA.Results Compared with the blank group,the model group exhibited gastric mucosal gland atrophy and extensive inflammatory cell infiltration,the contents of IL-1β,IL-18,GAS in serum significantly increased(P<0.01),the content of IL-10 and MTL significantly decreased(P<0.01),the mRNA expressions of HOXA-AS3,LTβR,NF-κB p65,NLRP3,IL-1β and IL-18 mRNA in gastric tissue significantly increased(P<0.05),the expression of miR-29a-3p significantly decreased(P<0.01),and the protein expressions of LTβR,p-IκBα,p-NF-κB p65,Caspase-1 and NLRP3 in gastric tissue significantly increased(P<0.01);after intervention with different dosages of Jianpi Tongluo Jiedu Prescription,pathological damage to the gastric mucosa was alleviated to varying degrees,the contents of IL-1β,IL-18,GAS in serum decreased,the content of IL-10 and MTL increased,the expression of mRNA and proteins related to the HOXA-AS3/miR-29a-3p/LTβR/NF-κB axis were reversed to varying degrees,among which Jianpi Tongluo Jiedu Prescription high-dose group showed statistical significance(P<0.05,P<0.01).Conclusion Jianpi Tongluo Jiedu Prescription can effectively improve pathological damage in gastric mucosal tissues of CAG rats,and its mechanism may be associated with the regulation of the HOXA-AS3/miR-29a-3p/LTβR/NF-κB axis.
李萌;罗楠;易柳凤;丁媛;于靖文;姜天童;王少丽;刘震
中国中医科学院广安门医院,北京 100053中国中医科学院广安门医院,北京 100053中国中医科学院广安门医院,北京 100053||北京中医药大学,北京 100029中国中医科学院广安门医院,北京 100053中国中医科学院广安门医院,北京 100053中国中医科学院广安门医院,北京 100053中国中医科学院广安门医院,北京 100053中国中医科学院广安门医院,北京 100053
医药卫生
慢性萎缩性胃炎健脾通络解毒方大鼠HOXA-AS3/miR-29a-3p/LTβR/NF-κB轴
chronic atrophic gastritisJianpi Tongluo Jiedu PrescriptionratsHOXA-AS3/miR-29a-3p/LTβR/NF-κB axis
《中国中医药信息杂志》 2026 (8)
64-70,7
国家自然科学基金面上项目(82174352)中央级公益性科研院所基本科研业务费专项资金(ZZ19-XRZ-047)
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