半夏调中颗粒调控NGF/TrkA通路改善内脏高敏感治疗非糜烂性反流病的机制研究OA

[Objective]To investigate the effect of Banxia Tiaozhong Granules(BXTZ)on the NGF/TrkA pathway in the esophagus and dorsal root ganglion(DRG)of rats with visceral hypersensitivity(VH)in non-erosive reflux disease(NERD),and to explore its therapeutic mechanism.[Methods]The 36 Sprague-Dawley(SD)rats were randomly assigned to six groups(n=6 per group):control,model,BXTZ,omeprazole,TrkA inhibitor(GW 441756),BXTZ+TrkA agonist(BXTZ+GA-amide).Except for the control group,all other groups were subjected to the establishment of a rat model of NERD with VH.After 14 days,the mechanical withdrawal threshold(MWT),vertical and horizontal activity scores were measured.The levels of serum NGF,PAR-2,and TRPV1 were detected.The protein expressions of NGF,TrkA,PAR-2,and TRPV1 in the esophagus and DRG were determined.The count and density of mast cells(MC)in the esophagus were recorded.Double immunofluorescence staining was used to detect the fluorescence intensities of NGF and TrkA in the esophagus.[Results]Compared with the blank group,the MWT value,horizontal score,and vertical score in the model group were significantly decreased(P<0.05),while the serum levels of NGF,PAR-2,and TRPV1,the protein levels of NGF,TrkA,PAR-2,and TRPV1 in the esophagus and DRG,the count and density of MC in the esophagus,and the fluorescence intensities of NGF and TrkA(in the esophagus)were significantly increased(P<0.05).Compared to the model group,the BXTZ group showed significantly increased MWT,vertical and horizontal activity scores(P<0.05),while the serum levels of NGF,PAR-2,and TRPV1,protein expressions of NGF,TrkA,PAR-2,and TRPV1 in the esophagus and DRG,count and density of esophageal MC,and fluorescence intensities of NGF and TrkA in the esophagus were significantly decreased(P<0.05).Intergroup comparisons showed that the BXTZ group had more significant increases in MWT,vertical and horizontal activity scores than the omeprazole group(P<0.05),and more significant increases in vertical and horizontal activity scores than the GW 441756 group(P<0.05).Additionally,the BXTZ group exhibited more significant decreases in serum,esophageal,and DRG levels of NGF,PAR-2,and TRPV1,as well as esophageal MC density,compared with the omeprazole group and GW 441756 group(P<0.05).The fluorescence intensities of NGF and TrkA in the esophagus of the BXTZ group were also more significantly reduced than those in the omeprazole group(P<0.05).[Conclusion]Banxia Tiaozhong Granules exerts a therapeutic effect on NERD by regulating the NGF/TrkA pathway,inhibiting MC activation and degranulation,and alleviating esophageal VH.