Phospholipid Enzyme A <sub> 2 </ Sub> Inhibitors Protective Effect And Mechanism Of Acute Ischemic Brain Damage

Phospholipase A2 (PLA2, EC3. 1.1.4) constitues a large and diverse family of enzymes that hydrolyze the sn-2 of fatty acid on phospholipids to release arachidonic acid (AA), prostagladins and leukotrienes from membrane phospholipids. PLA2 has been prosposed to play an important role in cerebral cell injury associated with ischemia. Therefore, investigation of PLA2 function and the protection effect of the PLA2 inhibitor in cerebral cell injury associated with ischemia are of great value in theoretical instruction sense and practical application. Rat middle cerebral artery occlusion model: 1. We observed the morphologic changes of cerebral cortex and examined the PLA2 activity, the expression of sPLA2 ~II A and cPLA2 mRNA in cerebral cortex, cytosolic free Ca2~ concentration in neuronal cells, the brain water content in 30 minutes, 60 minutes, 90 minutes, 120 minutes after cerebral middle artery occlussion. Our result: (1) Cerebra cortex cell swelling and edema were identified after middle cerebral artery occlussion. (2) The PLA2 activity, cytosolic free Ca2~+ concentration in neuronal cells, and brain water content were progressively increased from 30 minutes to 120 minutes after middle cerebral artery occlussion. (3) The brain water content was positively correlated with the cerebral cortex PLA2 activity and neuronal cells cytosolic free Ca2~ concentration in 120 minutes after middle cerebral artery occlussion. The cerebral cortex PLA2 activity was positively correlated with cytosolic free Ca2~+ concentration in neuronal cells. (4) The expression of sPLA2 II A and cPLA2 mRNA in cerebral cortex increased after cerebral artery occlussion. It demonstrated that: (1) PLA2 activation is involved in the process of cerebral cell ischemia injury .The severity of neuronal cell injury is closely related with the PLA2 activity. (2) Increased cytosolic free Ca concentration in neuronal cells after cerebral ischemia activates PLA2 and deteriorates cell injury. (3) The expression of PLA2 mRNA in cerebral cortex increased after cerebral ischemia. 2. After PLA2 inhibitor (Chloroquine) and/or calcium ion blocker 6 (Nimodipine) administration, We observed the morphologic changes of cerebral cortex, PLA2 activity and the expression of sPLA2 ~II A, cPLA2 rnRNA cerebral cortex, cytosolic free Ca concentration in neuronal cells, brain water content in 120 minutes after cerebral middle artery occlussion. It demonstrated that: Chloroquine can decrease PLA2 activity and the expression of sPLA2 - II A, cPLA2 mRNA in cerebral cortex after cerebral ischemia. Chloroquine similar to Nimodipine can significantly decrease PLA2 activity, cytosolic free Ca2~+ concentration in neuronal cells, brain water content after cerebral ischemia and alleviate brain edema. Since Chloroquine can decrease the expression of PLA2 mRNA in cerebral cortex after acute cerebral ischemia, it is suggested that Chloroquine have protective effect on cerebral cell injury associated with ischemia. Its protective effect consists of decreasing expression the of PLA2 mRNA and cytosolic free Ca concentration in neuronal cells, restraining PLA2 activity and alleviating brain edema ultimately.