Muscovite Ameliorates Diclofenac-Induced Small Intestinal Injury in Rats via the Inhibition of Protease-Activated Receptor 2 Activity

Abstract

Introduction: The pathogenesis of non-steroidal anti-inflammatory drugs(NSAIDs)- induced small intestinal lesions was still unclear, although it is consistent with recent capsule endoscopy evidence suggesting that NSAID-induced injury to the lower gut is much more prevalent than was once thought. Nonetheless, there is still no established strategy for the treatment and prevention of smallintestinal damage induced by NSAIDs. The aim of this study was to observe the effect of traditional Chinese medicine muscovite to diclofenac-induced small intestinal injury in rats. And to research the possible target spot in the prophylaxis and treatment of diclofenac-induced small intestinal injury by muscovite, in order to provide the further experimental basis for the treatment of NSAIDs enteropathy by TCM. Methods: Observed the small intestinal morphology by general damage score and Chiu score under light microscope of mucous membrane of small intestine. Observed cell ultrastructure by transmission electron microscope and scanning electron microscopy, tested portal endotoxin by dynamic turbidimetry, tested tryptase, PAR-2, ERK1/2, Occludin by immunohistochemistry, and analysed PAR-2 mRNA by real-time fluorescence quantification. Results: There were edema, scattered erosion and several superficial ulcer of mucous membrane of small intestine in muscovite group. The general score and tissue score in muscovite were lower than model group (P1.633 ±0.122) was lower than model group (P < 0.05), and the difference had statistical significance. Conclusion: We found that the total optical density of tryptase, PAR-2 protein and ERK1/2 in muscovite group were obviously lower than which in model group, occludin of mucous membrane of small intestine in muscovite was obviously higher than model group. The level of PAR-2 mRNA in muscovite groupwas lower than model group and the difference had statistical significance. This suggests that the prophylaxis and treatment of NSAID-induced intestinal damage by muscovite is related with active suppression of tryptase, reduction of PAR-2 excitation, and reduction of expression of ERK1/2 passageway with reducing the lesion of occludin.Figure 1Figure 2Figure 3