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AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease

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Angiotensin , which is the main effector of the reninangiotensin system, has an important role in intestinal inflammation via the angiotensin type 1 receptor (AT1R). The present study aimed to investigate the protective effects of the AT1R blocker losartan on 2,4,6trinitrobenzenesulphonic acid (TNBS)induced colitis. Losartan was administered to male adult C57BL/6 J mice 2 weeks prior to the induction of colitis, and images of the whole colon were captured to record changes, scored according to a microscopic scoring system, and reverse transcriptionquantitative polymerase chain reaction were performed in order to investigate colonic inflammation. In addition, intestinal epithelial barrier permeability was evaluated, and intestinal epithelial cell (IEC) apoptosis was measured using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and apoptosisrelated protein expression levels were detected by western blotting. Losartan was able to attenuate TNBSinduced body weight loss and colonic damage. Furthermore, T helper 1mediated proinflammatory cytokines were suppressed by losartan, and gut permeability was largely preserved. TUNEL staining revealed reduced IEC apoptosis in the losartantreated mice. Losartan also increased the Bcell lymphoma 2 (Bcl2)/Bcl2associated X protein (Bax) ratio and suppressed caspase3 induction. These results suggested that the AT1R blocker losartan may attenuate TNBSinduced colitis by inhibiting the apoptosis of IECs. The effects of losartan were partially mediated through increasing the Bcl2/Bax ratio and subsequently suppressing the induction of the proapoptotic mediator caspase3.
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Document Type: Research Article

Affiliations: 1: Department of Pediatric Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China 2: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China

Publication date: January 1, 2016

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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