Endothelial protective effect of simvastatin on coagulation system in septic rats / 中华内科杂志

ABSTRACT

Objective@#To investigate the endothelial protective effects of simvastatin on the coagulation system in septic rats.@*Methods@#A total of 54 SD male rats were divided into 3 groups. Six healthy rats were intraperitoneally injected with normal salineas control group. Twenty-four rats in septic group were intraperitoneally injected with normal saline followed by lipopolysaccharide 2.5 mg. Study group had 24 rats intraperitoneally injected with simvastatin followed by lipopolysaccharide. Plasma von Willebrand factor (vWF), thrombomodulin (TM), platelet activating factor (PAF) and antithrombin-Ⅲ (AT-Ⅲ) were tested at 1 h, 3 h, 6 h and 12 h after treatment. Scanning electron microscopy and transmission electron microscopy were used to observe the morphology and apoptosis of rat aorta endothelial cells.@*Results@#Compared with healthy control group, vWF [(68.3±4.8) ng/ml, (59.2±5.1) ng/ml, (74.2±20.1) ng/ml, (53.5±4.0)ng/ml, respectively], TM [(1.4±0.3) ng/ml, (1.6±0.4) ng/ml, (2.8±0.9) ng/ml, (1.4±0.5) ng/ml, respectively], PAF [(29.1±6.5) pg/ml, (28.6±1.5) pg/ml, (28.7±2.7) pg/ml, (18.2±4.1) pg/ml, respectively] and AT-Ⅲ [(262.2±38.1)μg/ml, (233.0±70.4) μg/ml, (218.7±54.7) μg/ml, (162.2±37.2) μg/ml, respectively] were significantly increased in the sepsis group at 1 h, 3 h, 6 h and 12 h (P<0.05). Compared with the sepsis group, the plasma levels of PAF in simvastatin intervention group at 1 h [(15.6±2.5) pg/ml, 3 h(10.4±5.3) pg/ml, 6 h (9.3±1.4) pg/ml, 12 h(11.0±2.7) pg/ml] were significantly decreased, so were the TM level at 6 h (1.6±0.9) ng/ml, and the AT-Ⅲ levels at 1 h[(190.3±29.2) μg/ml],6 h [(104.4±33.6) μg/ml] and 12 h [(73.6±39.0) μg/ml, P<0.05].@*Conclusion@#In the condition of sepsis, toxins and over-activated inflammatory factors damage the vascular endothelium. A large amount of circulating vWF, TM, PAF, and AT-Ⅲ cause early hypercoagulability. Simvastatin significantly reduces plasma amount of these procoagulants, suggesting it smodification of coagulopathy and vascular protective effectsin a septic rat model.