Objective To explore whether melatonin(Mel) can protect the intestinal barrier function of neonatal rats with necrotizing enterocolitis(NEC) by regulating the Akt/mTOR pathway.Methods Ninety newborn rats were randomly divided into normal group, model group, low(15 mg/kg) and high(30 mg/kg) dose Mel groups, and Mel(30 mg/kg) + Akti(Akt inhibitor, 5 μmol/L) group. Except for the normal group, NEC models were established in rats of the other 4 groups. After the experiment, the ocular venous blood was collected to detect the contents of serum D-lactic acid, diamine oxidase(DAO) and endotoxin. The ileocecum was retrieved for HE staining and detection of IL-6, IL-1β, TNF-α contents and autophagy gene(Beclin-1), LC3B, p-Akt/Akt, p-mTOR/mTOR expression levels.Results Compared with the normal group, the cells in ileocecum of the model group obviously showed degeneration and necrosis, mucosal muscular layer edema and loss of villi. Serum D-lactic acid, DAO, endotoxin content and intestinal tissue IL-6, IL-1β, TNF-α contents and Beclin-1, LC3B protein positive rates significantly increased(P<0.05), p-Akt/Akt and p-mTOR/mTOR levels were significantly reduced(P<0.05). Compared with the model group, the pathological changes of the ileocecal intestine tissue of the rats in the low and high dose Mel groups were significantly improved. Serum D-lactic acid, DAO, endotoxin content and IL-6, IL-1β, TNF-α contents and the positive rates of Beclin-1 and LC3B protein were reduced in sequence(P<0.05), p-Akt/Akt and p-mTOR/mTOR were increased(P<0.05). Compared with the Mel high-dose group, the ileocecal intestinal tissue lesions in the Mel+Akti group were worse. Serum D-lactic acid, DAO, endotoxin content and IL-6, IL-1β, TNF-α contents in intestinal tissue and the positive rates of Beclin-1, LC3B protein were significantly increased(P<0.05), p-Akt/Akt and p-mTOR/mTOR were significantly reduced(P<0.05).Conclusions Mel can up-regulate the expression of Akt/mTOR signaling pathway protein to inhibit autophagy and protect the intestinal barrier function of NEC neonatal rats.
Key words
melatonin /
protein kinase B/mammalian target of rapamycin signaling pathway /
necrotizing enterocolitis /
intestinal barrier
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