RESUMO
OBJECTIVE: This study observes the morphological changes in the enteric nervous system (ENS) - interstitial cells of Cajal (ICC) - smooth muscle cells (SMC) network in sphincter of Oddi dysfunction (SOD) in hypercholesterolemic rabbits following treatment with Shaoyao Gancao decoction (SGD), as well as the apoptosis of the ICC. METHODS: In this study, 48 healthy adult New Zealand rabbits are randomly divided into three groups (n = 16 in each group): the control, the model, and the SGD treatment groups. The hypercholesterolemic rabbit model is established. Hematoxylin and eosin staining, transmission electron microscopy, immunofluorescence, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, immunohistochemistry, Western blot analysis, and reverse transcription-polymerase chain reaction are used to detect the morphological changes in the ENS-ICC-SMC network, the expression of apoptosis-related proteins in the ICC, and to observe the curative effect of SGD after treatment. RESULTS: Compared with the control group, the morphology and the ultrastructure of the SO are destroyed in the model group. In addition, the protein gene product 9.5 (PGP9.5), nitric oxide (NO), the SMCs, and the ICC all significantly decreased while substance P (SP) significantly increased. Compared with the model group, the SO morphology and ultrastructure are repaired in the SGD group. In addition, the PGP9.5, NO, the SMCs, and the ICC significantly increased while SP decreased. In addition, SGD may activate the stem cell factor (SCF)/c-Kit signaling pathway to treat SO dysfunction by up-regulating the expression of c-Kit and SCF. Similarly, this pathway restores SO by up-regulating the expression of Bcl2 and inhibiting cleaved caspase-3, Bax, and the tumor necrosis factor. CONCLUSION: Shaoyao Gancao decoction can promote the recovery of sphincter of Oddi dysfunction in hypercholesterolemic rabbits by protecting the ENS-ICC-SMC network.
RESUMO
Pancreatic cancer (PC) is the fourth most common cause of cancerrelated mortality in the industrialized world. Emerging evidence indicates that a variety of microRNAs (miRNAs or miRs) are involved in the development of PC. The aim of the present study was to elucidate the mechanisms through which miR494 affects the epithelialmesenchymal transition (EMT) and invasion of PC cells by binding to syndecan 1 (SDC1). PC tissues and pancreatitis tissues were collected, and the regulatory effects of miR494 on SDC1 were validated using bioinformatics analysis and a dualluciferase report gene assay. The cell line with the highest SDC1 expression was selected for use in the following experiments. The role of miR494 in EMT was assessed by measuring the expression of SDC1, Ecadherin and vimentin. Cell proliferation was assessed using a cell counting kit (CCK)8 assay, migration was measured using a scratch test, invasion was assessed with a Transwell assay and apoptosis was detected by flow cytometry. Finally, a xenograft tumor model was constructed in nude mice to observe tumor growth in vivo. We found that SDC1 protein expression was significantly higher in the PC tissues. SDC1 was verified as a target gene of miR494. The SW1990 cell line was selected for use in further experiments as it had the lowest miR494 expression and the highest SDC1 expression. Our results also demonstrated that miR494 overexpression and SDC1 silencing significantly decreased the mRNA and protein expression of SDC1 and vimentin in SW1990 cells, while it increased Ecadherin expression and apoptosis, and inhibited cell growth, migration, invasion and tumor growth. On the whole, the findings of this study demonstrated that miR494 is able to downregulate SDC1 expression, thereby inhibiting the progression of PC. These findings reveal a novel mechanism through which miR494 affects the development of PC and may thus provide a basis for the application of miR494 in pancreatic oncology.