Effect of therapy for removing stasis and protecting mucosa on E-cadherin expression and esophageal mucosal repair in rats with reflux esophagitis via PI3K/Akt pathway
Objective It is to explore the effects of therapy for removing stasis and protecting mucosa(RSPM)on e-sophageal mucosal injury in rats with reflux esophagitis(RE)via regulating the expression of E-cadherin by PI3K/Akt sig-naling pathway,and further clarified its mechanism.Methods A total of 68 male SD rats were selected,in which 10 rats were randomly selected as sham operation group,and the remaining rats were treated with4.2 mm pyloric clamp+2/3 gas-tric fundus ligation to establish RE models.56 successfully modeled rats were randomly divided into 7 groups,with 8 rats in each group.The rabeprazole group was given 0.001 8 g/kg of rabeprazole by gavage,the Almagate group was given 0.0135 g/kg of Almagate suspension by gavage,and the rabeprazole+RSPM group was given 0.0018 g/kg of rabeprazole+1.62 g/kg of RSPM Paste by gavage,the rabeprazole+modified RSPM group was given 0.0018 g/kg of rabeprazole+2.97 g/kg of modified RSPM Paste by gavage,the RSPM group was given 1.62 g/kg of RSPM Paste by gavage,the modified RSPM Paste group was given 2.97 g/kg of modified RSPM Paste by gavage,the sham operation group and model group were given distilled water+starch by gavage,all once daily,continuously gavage for 14 days.The general situation of the rats was ob-served.After the last gavage,the whole stomach was removed to calculate the residual rate of pigment in the stomach.The pathological morphology of esophageal tissue was observed by HE staining,the structure of Cajal interstitial cells in esopha-geal tissue was observed by transmission electron microscopy,and the mRNA expressions of E-cadherin and Slug in esopha-geal tissue were detected by RT-PCR,the protein expressions of E-cadherin,Caspase-1,p-PI3K,p-Akt,PTEN and PDK1 were detected by Western blot,the positive expressions of E-cadherin,Caspase-1,PTEN and PDK1 in esophageal tissues were detected by immunohistochemistry,the serum levels of Caspase-1,IL-1β,IL-17,IL-18 and IL-23 were detected by ELISA.Results Compared with the sham operation group,the stomach pigment residual rate of rats in the model group was significantly increased(P<0.05);there was inflammatory cell infiltration,slight thickening of mucosal layer and de-creased number of Cajal interstitial cells in esophageal tissue;the relative expression of E-cadherin mRNA and relative ex-pressions of E-cadherin and PTEN proteins,and the positive expression area rates of E-cadherin and PTEN in esophageal tissues were significantly decreased(all P<0.05),while the relative expression of Slug mRNA,the relative expressions of Caspase-1,p-PI3K,p-Akt and PDK1 proteins,and the positive expression area rates of Caspase-1 and PDK1 were signifi-cantly increased(all P<0.05);the serum levels of Caspase-1,IL-1β,IL-17,IL-18 and IL-23 were significantly in-creased(all P<0.05).Compared with the model group,the the stomach pigment residual rate of rats in each treatment group were significantly decreased(all P<0.05);the esophageal tissue injury was significantly alleviated;the relative ex-pression of E-cadherin mRNA,the relative expressions of E-cadherin and PTEN proteins,and the positive expression area rates of E-cadherin and PTEN in esophageal tissues of the rabeprazole+RSPM group and rabeprazole+modified RSPM group were significantly increased(all P<0.05),while the relative expression of Slug mRNA,the relative expressions of Caspase-1,p-PI3K,p-Akt and PDK1 proteins,and the positive expression area rates of Caspase-1 and PDK1 were signifi-cantly decreased(all P<0.05);the serum levels of Caspase-1,IL-1β,IL-17,IL-18 and IL-23 were significantly de-creased(all P<0.05).Compared with the rabeprazole group,the relative expression of E-cadherin mRNA,the relative expressions of E-cadherin and PTEN proteins,and the positive expression area rates of E-cadherin and PTEN in esophageal tissues of rabeprazole+RSPM group and rabeprazole+modified RSPM group were significantly increased(all P<0.05);the relative expression of Slug mRNA,the relative expressions of Caspase-1,p-PI3K and p-Akt proteins,and the positive expression area rates of Caspase-1 and PDK1 were significantly decreased(all P<0.05);the relative expression of PDK1 protein and serum levels of Caspase-1,IL-1β,IL-17,IL-18 and IL-23 in esophageal tissue of rabeprazole+modified RSPM group were significantly decreased(all P<0.05).The relative expressions of p-PI3K and p-Akt protein in esophageal tis-sue and serum levels of Caspase-1,IL-1β,IL-17,IL-18 and IL-23 in rabeprazole+modified RSPM group were significant-ly lower than those in rabeprazole+RSPM group(all P<0.05).Conclusion Therapy for RSPM can inhibit the over-acti-vation of PI3K/Akt pathway on E-cadherin and Slug transcription factors,down-regulate the expressions of Caspase-1,p-PI3K,p-Akt and PDK1,and up-regulate the expressions of E-cadherin and PTEN proteins,thus to reduce serum levels of Caspase-1,IL-1β,IL-17,IL-18 and IL-23,alleviate the inflammatory lesions of epithelial cells and(or)inhibit the metastasis and infiltration of cells,and promote the repair of esophageal mucosa.The curative effect is better when com-bined with western meidicne,and the optimization of prescription can be more obvious.
reflux esophagitisesophageal mucosaltherapy for removing stasis and protecting mucosaPI3KAktE-cadherin
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