Role Of Artemisinin In The Protection Of Septic Rats

Objective: Sepsis is a common inflammation syndrome induced by infection. Severe sepsis and septic shock are life threatening complications of infections and a common cause of death in intensive care units. Recent US and European surveys estimate that severe sepsis accounts for 2-11% of all admissions to hospitals or intensive care units. Despite improved supportive care, the hospital mortality rate increase from severe sepsis and septic shock (30% and over 60%, respectively). Unfortunately, many experimental inflammatory antagonist-based therapies have failed in sepsis trials, and there are currently no effective anti-sepsis drugs in clinical use.Artemisinin (ART),an effective monomer isolated from artemisia annua L, is traditionally used for treating resistant malaria. It was reported that ART and its derivatives inhibited inflammation response induced by endotoxin. In present study, an animal rat sepsis model was made by cecal ligation and puncture (CLP), and the effect of ART was observed.Methods:①Three kinds of transfixion pin were used to make CLP in order to observe the three-day mortality of CLP.②The protection of ART on CLP rats was observed. Meanwhile, the plasma LPS, TNF-αand IL-6 of rats with or without treatment by ART were tested at the time-points of 2, 6, 12, 24, 48 and 72h . The contents of TNF-α, IL-6, superoxide dismutase (SOD) and malondialdehyde (MDA) in hepatic tissue were tested, too. The morphological changes of intestinal mucosa were observed using light microscope and transmission electron microscope (TEM).③In vitro, the peritoneal macrophages (PMφ) isolated from rats. After exposured to LPS (100ng/ml) or heat-killed E.coli, the contents of TNF-αand IL-6 in supernatants were tested by ELISA.Result:①The stable CLP rat model was established.②The three-day mortality in the ART group was significantly lower than that in the CLP group (p<0.01). The treatment of ART significantly reduced the peak plasma concentrations of LPS, TNF-αand IL-6 in the CLP rats(p<0.05 or p<0.01)and the contents of MDA, TNF-αand IL-6 in the hepatic tissue. But the level of SOD is very higher at 12 h.③In vitro, the treatment of murine...