The study aims at elucidating the mechanism involved in the cell dysfunction or impairment and the protective effects of
phospholipase A2 (PLA2) inhibitors in
endotoxin shock. Thirty-four rabbits were divided randomly into four groups: (1) normal control group (NC, n = 6), receiving saline intravenously; (2)
endotoxin shock group (ES, n = 12), receiving 3 mg/kg of E. coli
endotoxin; (3)
chloroquine pretreated group (CQ, n = 8), receiving 3 mg/kg of
chloroquine 3 min before
endotoxin injection and (4)
chlorpromazine pretreated group (CPZ, n = 8), receiving 0.3 mg/kg of
chlorpromazine 30 min before
endotoxin injection. Hepatic mitochondria were extracted either 8 h after commencement of the experiment or when the animals died for detecting PLA2 activity, membrane fluidity, membrane bound
succinate dehydrogenate (SDH) and
malondialdehyde (MDA). Mitochondria of the lung, heart and kidney were also used for detection of the membrane fluidity. It was revealed that the survival rate of 8 h was 100% (NC), 58% (ES), 87.5% (CQ) and 75% (CPZ), respectively. Mean arterial pressure (MAP) dropped soon after
endotoxin injection and descended continuously afterwards in the ES group (P < 0.01). Fluorescence polarization, microviscosity and anisotrophy with a DPH probe were elevated above control levels (P < 0.01). SDH was decreased obviously following
endotoxin infusion (P < 0.01).
Chloroquine and
chlorpromazine, serving as PLA2 inhibitors, could abate cellular dysfunction and increase survival rate. It is proposed that PLA2 plays a pivotal role in cellular injury in
endotoxin shock. PLA2 inhibitor might serve as a useful adjunct in combating
sepsis and
shock.