Simvastatin nanoparticles attenuated intestinal ischemia/reperfusion injury by downregulating BMP4/COX-2 pathway in rats

• Main Authors: Tong F, Dong B, Chai R, Tong K, Wang Y, Chen S, Zhou X, Liu D
• Format: Article
• Language: English
• Published: Dove Medical Press 2017-03-01
• Series: International Journal of Nanomedicine
• Subjects: PEG-b-PBLG50; II/RI; simvastatin; BMP4; COX-2
• Online Access: https://www.dovepress.com/simvastatin-nanoparticles-attenuated-intestinal-ischemiareperfusion-in-peer-reviewed-article-IJN

Fei Tong,1 Bo Dong,1 Rongkui Chai,1 Ke Tong,2,3 Yini Wang,4 Shipiao Chen,1 Xinmei Zhou,1 Daojun Liu5 1Department of Pathology and Pathophysiology, Provincial Key Discipline of Pharmacology, Jiaxing University Medical College, Jiaxing, Zhejiang, 2College of Life Science and Engineering, 3State Defense Key Laboratory of Fundamental Science on Nuclear Wastes and Environment, Southwest University of Science and Technology, Mianyang, Sichuan, 4Department of Nursing, Zhejiang Rongjun Hospital, The Third People’s Hospital of Jiaxing, Jiaxing, Zhejiang, 5Department of Pharmacochemistry, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: The purpose of the research was to explore the therapeutic action of simvastatin-loaded poly(ethylene glycol)-b-poly(gamma-benzyl l-glutamate) (PEG-b-PBLG50) 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-PBLG50 (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-α, 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. Keywords: PEG-b-PBLG50, II/RI, simvastatin, BMP4, COX-2