Mechanisms Underlying Prophylaxis And Treatment Of LPS-induced Mouse Multiple Organ Failure With Qingre Jiedu Liqi Huoxue Decoction

Septic shock and sequential multiple organ dysfunction syndrome (MODS) is themain cause of death in patients with sepsis. Despite recent progress in antibiotics andcritical care therapy, mortality rate from sepsis is still 40%-60%. It is reported that45%-60% patients with sepsis are caused by Gram-negative bacterial infection,endotoxin or lipopolysaccharide (LPS) plays an important role in the Gram-negativebacterial infection- induced systemic inflammatory response syndrome (SIRS). Sincethe 1980s, the great progress has been made in molecular mechanisms of septic shockand MODS, especially LPS-mediated signal transduction pathway. These researcheshave resulted in clinical investigation of a munber of agents, which antagonize a singlemediator in SIRS, such as antibody to LPS, interleukin (IL)-1 receptor antagonist,antibody to tumor necrosis factor (TNF), endothelin receptor antagonists and inhibitorsof nitric oxide synthase. However, none of these agents has shown to decrease themortality rate of sepsis in clinical trials. Recent researches suggest a combination ofseveral therapies or multifunction agents may be an important strategy for thetreatment of LPS-induced multiple organ failure. Chinese herbal medicine hasmultifunctional actions, many investigations are focused on the use of Chinese herbalmedicine to treat LPS- induced shock in recent 20 years, but it remains to be furtherstudy which treatment method in traditional Chinese medicine and which Chineseherbal decoction can improve survival from LPS-induced shock In order to provide a new Chinese medicine to reduce the mortality rate of micechallenged with LPS, the aim of this study was to observe the effects of HuanglianJiedu decoction (HJ), Renshen Sini decoction (RS), Shenfuqing decoction (SF),Shenfuqing Danshen decoction (SFD), Qingre Jiedu Liqi Huoxue decoction (QL,consisting of rhizoma coptidis, radix paeoniae rubra, radix cynanchi atrati, fructusaurantii immaturus, radix notoginseng, etc.) on LPS-induced MODS and mortality inmice, and further investigate the mechanisms in which QL prevents LPS-inducedmultiple organ failur and improves survival in LPS-treated mice. This study included three parts: Firstly, we examined the effects of Huanglian Jiedu decoction (HJ), RenshenSini decoction (RS), Shenfuqing decoction (SF), Shenfuqing Danshen decoction (SFD)on the survival rate of mice challenged with LPS. Mice were randomly divided into 6 groups, control, LPS, HJ, RS, SF and SFD清热解毒理气活血方药防治 LPS 性多器官功能衰竭的机制研究 6treatment group. In detail, Mice were administered intragastrically with distilled water(0.2 ml/10g) or RS, HJ, SF and SFD twice a day for 3 days, two hours after Chineseherbal medicine treatment on day 3, LPS (60 mg/kg) or normal saline was injectedintraperitoneally (ip), and survival rate in each group was recorded at 12-h intervals. The results showed LPS (60 mg/kg) caused a decrease in survival rate of mice,HJ, RS, and SF all didn't improve survival of mice exposed to LPS, while SFDenhanced mortality rate of mice treated with LPS. These results indicate that earlytreatment with Chinese medicine therapeutic method of clearing away heat andremoving toxic substances or warming Yang to treat collapse or combination ofwarming Yang to treat collapse and regulating Qi flow to promote blood circulation didnot improve survival of mice challenged with LPS, and suggest that it is veryimportant to understand the interaction of Chinese herbal drugs for the treatment ofLPS-induced MODS. Secondly, we observed the effects of QL on mortality, multiple organdysfunction and histological and ultrastructure changes in mice challenged with LPS. Experiment 1: Mice were randomly divided into 4 groups, control, LPS,QL+LPS and QL group. Mice were administered intragastrically with QL at a dose of1 g/mL (0.2 ml/10g) or distilled water (0.2 ml/10g) twice a day for 3 day...