Subcellular membrane impairment and application of phospholipase A2 inhibitors in endotoxic shock.
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.
Song
S M
SM
Research Institute of Surgery, Chongqing, People's Republic of China.
Lu
S M
SM
Wang
Z G
ZG
Liu
J C
JC
Guo
S Q
SQ
Li
Z
Z
D000818:Animals; D002738:Chloroquine / Q000627:therapeutic use; D002746:Chlorpromazine / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D007425:Intracellular Membranes / Q000187:drug effects* / Q000502:physiology; D008560:Membrane Fluidity / Q000187:drug effects* / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000502:physiology; D054467:Phospholipases A2; D011817:Rabbits; D012772:Shock, Septic / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*
D004791:Enzyme Inhibitors; D002738:Chloroquine; D010741:Phospholipases A; D054467:Phospholipases A2; D002746:Chlorpromazine