The Expression Of Long Non-coding RNA-ncRuPAR In Intestinal Epithelial Injury Induced By Nonsteroidal Anti-inflammatory Drugs And The Intervention Mechanism Of Mica

Objective To observe the villi,tight connections and ultrastructural changes of small intestinal epithelial cell in patients with long-term use of NSAIDs;To elucidate the expression levels of nc Ru PAR and PAR-2 in intestinal epithelial cells of patients with long-term use of NSAIDs and the intervention mechanism of mica.Methods 1.Small intestinal tissue were collected from patients with long-term use of NSAIDs and healthy volunteers,then the villi,tight connections and ultrastructure of small intestinal epithelial cell were observed by transmission electron microscopy.2.Caco-2 cells were cultured and divided into the following four groups: group A: blank control group;Group B: diclofenac sodium treatment group;Group C: diclofenac sodium+mica containing serum group;Group D: diclofenac sodium treatment+PAR-2 blocker FSLLRY-NH2 group.Transwell detected the intestinal epithelial cell permeability,western-blot detected the expression levels of PAR-2,Occludin and Claudin-1,and q RT-PCR detected the expression levels of nc Ru PAR and PAR-2 m RNA.Results 1.Electron microscopic observation of small intestinal tissue in patients long-term use of NSAIDs showed that the villi of small intestinal epithelial cell were shortened,disorderly and prostrate,and some of them were absent.The tight connection widened and the desmosome decreased.The normal structure of mitochondria disappeared,and the structure of cristae was disordered and disappeared.2.After diclofenac sodium treatment,intestinal epithelial cell permeability increased,the expression of Occludin and Claudin-1 decreased.Besides,the expression of nc Ru PAR and PAR-2 also increased.Mica medicated serum and PAR-2 blocker FSLLRY-NH2 inhibited the increase of intestinal epithelial cell permeability induced by diclofenac sodium,as well as its effect on the expression of nc Ru PAR,PAR-2,Occludin and Claudin-1.Conclusion People who have been taking NSAIDs for a long time,the villi of the small intestinal epithelial cell were damaged,the tight connections were widened,the desmosomes were reduced,and the normal structure of mitochondria disappeared.After diclofenac sodium treatment,the expression of nc Ru PAR and PAR-2 in Caco-2 cells were up-regulated,while the intestinal epithelial cell permeability was increased,tight connections were impaired,and intestinal mucosal mechanical barrier function was impaired.Mica may play a role in protecting the mechanical barrier function of intestinal mucosa by targeting nc Ru PAR so as to reduce the expression of PAR-2.