Mechanisms For A Decrease In Mortality Of LPS-challenged Mice By Rhynchophylline

ObjectiveTo observe effect of rhynchophylline(Rhy) on mortality and organ injury in endotoxemic mice and further investigate the mechanisms of its actions.MethodsThis study includes five parts:Firstly,we examined the effects of rhynchophylline on the mortality of mice challenged with LPS.Secondly,we determined the heart function at 12 h after LPS administration with VisualSonics^? Vevo770^? High-Resolution In Vivo Imaging System.Thirdly,mice were sacrificed at 12 h after LPS administration,and lung,liver,kidney and small intestine were collected for the HE staining,and the histological changes of the above organs were observered.Fourthly,we investigated the effect of Rhy on serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-10(IL-10) and nitric oxide(NO) contents in LPS-challenged mice with enzyme-linked immunosorbent assay(ELISA) and the technique of nitrate reductase.Lastly,the effect of Rhy on survival rate of mice subjected to cecal ligation and puncture(CLP) was also investigated.Results1.Pretreatment with rhynchophylline decreased the mortality of the endotoxemic BALB/c mice in a does-dependent manner,the efficiency of pretreatment with rhynchophylline at a dose of 8 mg/kg or 16 mg/kg was better,the mortality at 24 h after LPS administration decreased by 36.3%compared with the mortality of LPS-challenged mice.The survival rate of mice pretreated with rhynchophylline at a dosage of 8 mg/kg was higher 6 days after LPS challenge than that of LPS-challenged mice(P＜0.05).Pretreatment with 16 mg/kg Rhy also reduced the mortality of endotoxemic Kunming mice,the mortality was 43%,which was lower than that of mice treated with LPS alone(P＜0.05).2.Pretreatment with rhynchophylline had no obvious improvement in the lung,liver,kidney and intestine tissue injury,and no significant depression in the lung W/D ratio and the serum activities ofALT,AST and the level of BUN and Cr in Kunming mice theated with LPS.3.Pretreatment with rhynchophylline could elevate the systole function of cardiac muscle of the endotoxemic Kunming mice and improve the heart function of the endotoxemic Kunming mice.4.There was a distinct decrease in serum TNF-αin rhynchophylline pretreatment group compared with LPS group,but no significant effect in level of serum IL-1β,IL-10 and NO; there were distinct decreases of TNF-αand IL-1βin the cardiac muscle in rhynchophylline pretreatment group compared with LPS group,but no significant depression in the level of NO.5.Rhynchophylline did not improve the survival in the Kunming mice subjected to CLP.ConelusionRhynchophylline decreases the mortality and enhance systole function of cardiac muscle in LPS-challenged mice,which may be related to its decreasing level of TNF-αand IL-1βduring endotoxemia.However,Rhy does not reduce the mortality of mice subjected to CLP.