Effects of atorvastatin combined with low-molecular-weight heparin on plasma inflammatory cytokine level and pulmonary pathophysiology of rats with sepsis

Fei Jing; Ming Li; Hongsheng Ren; Jitian Zhang; Qingchun Yao; Yufeng Chu; Chunting Wang

doi:10.3892/etm.2016.3372

Effects of atorvastatin combined with low-molecular-weight heparin on plasma inflammatory cytokine level and pulmonary pathophysiology of rats with sepsis

Exp Ther Med. 2016 Aug;12(2):1048-1054. doi: 10.3892/etm.2016.3372. Epub 2016 May 20.

Authors

Fei Jing¹, Ming Li², Hongsheng Ren³, Jitian Zhang⁴, Qingchun Yao³, Yufeng Chu³, Chunting Wang³

Affiliations

¹ Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
² Department of Rheumatology and Clinical Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
³ Department of Intensive Care Unit, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
⁴ Department of Nutrition, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.

Abstract

The aim of the present study was to investigate the effect of atorvastatin combined with low-molecular-weight heparin (LMWH) on plasma early inflammatory cytokine levels as well as pulmonary pathophysiology of rats with sepsis. A total of 122 rats were randomly divided into five groups including the sham operation group (n=10), CLP group (n=10), atorvastatin group (n=34, 20 mg/kg/day), LMWH group (n=34, 100 IU/kg/day), and atorvastatin combined with LMWH group (n=34). Blood samples from 6 rats in each group were collected to detect TNF-α, IL-1β and HMGB1 concentration in plasma by linked immunosorbent assay at baseline and postoperatively at 4, 8, 12 and 24 h. Pulmonary pathophysiology was observed postoperatively at 24 h. The remaining 10 rats in each group were used to calculate the 7-day cumulative mortality rate. Compared to the sham operation group, the scores in CLP were greater than those of the sham operation group (P<0.05). Compared to the CLP group, the sepsis severity scores of the atorvastatin, LMWH, and atorvastatin combined with LMWH groups decreased gradually. Significant difference was detected in the four groups (P<0.05 0.01). Compared to the sham operation group, at 4, 8, 12 and 24 h, the TNF-α, IL-1β and HMGB1 levels in plasma in CLP increased significantly (P<0.01). Compared to the CLP group, the TNF-α, IL-1β and HMGB1 levels of plasma in other groups decreased gradually, and there was a significant difference in the four groups (P<0.01). At 24 h post operation, compared to the sham operation group, the damage of pulmonary pathophysiology in CLP was more severe. Compared to the CLP group, the damage of pulmonary pathophysiology in other groups was slight. Compared to the CLP group, the 7-day cumulative mortality rate in other groups decreased significantly (P<0.05). In conclusion, atorvastatin, combined with LMWH can decrease sepsis severity, plasma inflammatory cytokine levels, pulmonary pathophysiology, and the 7-day cumulative mortality rate. Atorvastatin, and LMWH may therefore be useful for the treatment of sepsis due to its ability to inhibit the release of TNF-α, IL-1β and HMGB1 in septic rats.

Keywords: atorvastatin; cecal ligation and puncture; cumulative mortality rate; inflammatory cytokines; low-molecular-weight heparin; pulmonary pathophysiology; sepsis rats; sepsis severity.