Pretreatment of vitamin D3 ameliorates lung and muscle injury induced by reperfusion of bilateral femoral vessels in a rat model.
BACKGROUND
Peripheral arterial occlusive disease (PAOD) is a challenge in peripheral vascular disease. Clinical observations show reperfusion of occluded vessels may cause compartment syndrome or remote organ injury. Less well known is the role of vitamin D3 in tissue injury; therefore, we attempted to determine whether vitamin D3 could alleviate local and remote organ injury induced by reperfusion of occluded vessels in animal models.


METHODS
Twenty-four male Sprague-Dawley rats were randomized into four groups: saline + sham, saline + I/R, vitamin D3 + sham, and vitamin D3 + I/R group. After pretreatment for 5 d, the animals designed to I/R injury were subjected to 3 h of ischemia induced by bilateral femoral arteries clamp, followed by reperfusion of the vessels for 3 h on d 6. Left lung and left anterior tibial muscle tissue were harvested for wet/dry weight ratio and histopathologic analysis. Blood was collected for analysis of urea nitrogen (BUN), creatinine (Cr), aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), ionized calcium levels, and heme oxygenase-1 (HO-1).


RESULTS
Compared with the saline + sham group, there was a significant increase in plasma IL-6 level in both saline + I/R and vitamin D3 + I/R groups and muscle, lung wet/dry weight ratio in the saline + I/R group (P < 0.05). Compared with the saline + I/R group, there was a significant decrease in plasma IL-6 level, muscle and lung wet/dry weight ratio in both vitamin D3 + sham and vitamin D3 + I/R groups, and leukocyte HO-1 expression in vitamin D3 + sham group (P < 0.05). Compared with the vitamin D3 + sham group, there was a significant increase in plasma IL-6 levels in the vitamin D3 + I/R group, and leukocyte HO-1 expression in vitamin D3 + sham group (P < 0.05). BUN, Cr, AST, ALT, TNF-α, ionized calcium levels did not differ significantly among the groups.


CONCLUSIONS
Pretreatment of vitamin D3 ameliorates the systemic IL-6 levels, lung and muscle injury induced by ischemia followed by reperfusion of bilateral occluded vessels in a rat model.
Shih
Pin-Keng
PK
Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Chen
Yi-Ching
YC
Huang
Ya-Chun
YC
Chang
Yu-Tang
YT
Chen
Jian-Xun
JX
Cheng
Chih-Mei
CM
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000188:drug therapy*; D002118:Calcium / Q000378:metabolism; D002762:Cholecalciferol / Q000494:pharmacology*; D003161:Compartment Syndromes / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D005263:Femoral Artery; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D006614:Hindlimb / Q000098:blood supply; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014815:Vitamins / Q000494:pharmacology
D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014815:Vitamins; D002762:Cholecalciferol; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D002118:Calcium