title: Simvastatin inhibits inflammation in ischemia-reperfusion injury.
abstract: Ischemia/reperfusion (I/R) is associated with leukocyte accumulation and tissue injury. The aim of this research was to investigate the protective effect of simvastatin on hind limb I/R inflammation and tissue damage. Mice were subjected to hind limb ischemic insult for 2 h and were simultaneously administered an intraperitoneal injection of simvastatin (5 mg/kg); this was followed by 36 h of reperfusion. Myeloperoxidase (MPO) levels in the muscles of the hind limb were determined. CXC chemokines and pro-inflammatory cytokines, such as macrophage inflammatory protein (MIP)-2, cytokine-induced neutrophil chemoattractant (KC), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and P-selectin, were assessed using enzyme-linked immunosorbent assay (ELISA). Leukocyte rolling and adhesion in vitro was assessed to indicate leukocyte recruitment at the site of inflammation. Quantitative measurement of skeletal muscle tissue injury was performed. The fluorescent dye level in tissue and serum was used to determine hind limb vascular leakage and tissue edema after I/R. Systemic and differentiated leukocytes were also counted. Simvastatin significantly reduced MIP-2, KC, TNF-α, MPO, IL-6, and P-selectin levels compared to the sham group and I/R plus pretreatment with phosphate-buffered saline (PBS) group (P<0.05). Compared to the sham group and I/R plus PBS group, the I/R plus simvastatin group had attenuated inflammation, vascular leakage, and muscular damage (P<0.05). Simvastatin also significantly inhibited leukocyte rolling and adhesion compared to PBS (P<0.05). Our results suggest that simvastatin may be an effective protectant against tissue injury associated with I/R.
authors.affiliation: Department of Oncological and Vascular Interventional Radiology, Zhongshan Hospital, Xiamen University, Xiamen, China.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Zhao
authors.forename: Qingzhao
authors.initials: Q
authors.lastname: Feng
authors.forename: Zhengjie
authors.initials: Z
authors.lastname: Huang
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Li
authors.forename: Baisheng
authors.initials: B
authors.lastname: Chen
authors.forename: Long
authors.initials: L
authors.lastname: Jiang
authors.forename: Binglin
authors.initials: B
authors.lastname: Wu
authors.forename: Weiji
authors.initials: W
authors.lastname: Ding
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.forename: Heng
authors.initials: H
authors.lastname: Pan
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Weiyuan
authors.initials: W
authors.lastname: Luo
authors.forename: Qi
authors.initials: Q
authors.lastname: Luo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D019821:Simvastatin