Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 12, Issue -, Pages 2477-2488Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S126063
Keywords
PEG-b-PBLG(50); II/RI; simvastatin; BMP4; COX-2
Funding
- Department of Education, Zhejiang Government
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The purpose of the research was to explore the therapeutic action of simvastatin-loaded poly(ethyleneglycol)-b-poly (gamma-benzyl L-glutamate) (PEG-b-PBLG(50)) on intestinal ischemia/reperfusion injury (II/RI) through downregulating bone morphogenetic protein 4 (BMP4)/cyclooxygenase-2 (COX-2) pathway as compared to free simvastatin (Sim). Sprague Dawley rats were preconditioned with 20 mg/kg Sim or simvastatin/PEG-b-PBLG(50) (Sim/P) compounds, and then subjected to 45 min of ischemia and 1 h of reperfusion. The blood and small intestines were collected, serum levels of interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha, and nitric oxide (NO) were checked, and the dry/wet intestine ratios, superoxide dismutase activity, myeloperoxidase content, reactive oxygen species, endothelial nitric oxide synthase, protein 47 kDa phagocyte oxidase (p47phox), BMP4, COX-2, and p38 mitogen-activated protein kinase (p38MAPK) expressions were measured in intestinal tissues. Both Sim and Sim/P pretreatment reduced intestinal oxidative damnification, restricted inflammatory harm, and downregulated the BMP4 and COX-2 expressions as compared to II/RI groups, while Sim/P remarkably improved this effect.
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