Affiliation:
1. Department of Gastroenterology The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology Kunming Yunnan China
2. Department of Hepatobiliary Surgery The Second Affiliated Hospital of Kunming Medical University Kunming China
3. Department of Thoracic Surgery The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology Kunming Yunnan China
Abstract
AbstractBackground and aimsTraumatic brain injury (TBI) is the main cause of death and can lead to a variety of physiological complications, including gastrointestinal dysfunction. The present study aimed to confirm the miR‐19a‐mediated suppression of diarrhea after TBI through the regulation of VIP expression.MethodsA rat model of TBI induced by controlled cortical injury was used to observe gastrointestinal morphology by opening the abdomen after TBI. After 72 h of injury, the fecal water content of the rats was measured. The end ileal segments were removed, and HE staining was used to observe the histopathological changes in the intestine. The levels of serum miR‐19a and VIP mRNA were detected by qRT‐PCR. ELISA was performed to detect VIP levels in serum. Immunohistochemistry was used to detect the level of VIP in ileal tissues, and immunofluorescence was used to detect c‐kit expression in ileal tissue. CCK‐8 assay was used to detect the cell viability of interstitial cells of Cajal (ICCs), and TUNEL assay was used to detect apoptosis of ICCs.ResultsmiR‐19a and VIP were highly expressed in the serum of TBI rats, and the knockdown of miR‐19a alleviated TBI‐induced diarrhea. In addition, the overexpression of miR‐19a or VIP inhibited the proliferation of ICCs, promoted apoptosis, and suppressed intracellular Ca2+ levels, whereas miR‐19a suppression had the opposite effects. A nonselective nitric oxide synthase inhibitor (L‐NA), PKG inhibitors (KT‐5823 and RP‐8CPT‐cGMPS), and a guanylate cyclase inhibitor (ODQ) restored the inhibitory effects of VIP on ICC proliferation, anti‐apoptosis effects, and Ca2+ concentrations.ConclusionKnockdown of miR‐19a inhibits activation of the VIP–NO–cGMP–PKG pathway through suppression of VIP expression, which in turn inhibits diarrhea after TBI.
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