Activation of phospholipase A2, changes of free ca2+ concertration and protection of nimodipine in rats with acute cerebral ischemia injury

Xingyong WANG; Xiaowen LI; Zhongyi LU; Fengwu KUANG; Feng XU

ABSTRACT

BACKGROUND:

Activated by Ca2+, phospholipase A2 will aggravate the influx of Ca2+ or the release of intracellular Ca2+, and then forms a vicious circle, which results in a continuous increase in free calcium level and leads to server injury in neural cells.

OBJECTIVE:

To discuss the protective effects of nimodipine on acute ischemic brain injury caused by activation of phospholipase A2.

DESIGN:

A completely randomized controlled trial.

SETTING:

Intensive Care Unit (ICU) of Children's Hospital, Chongqing Medical University.MATERIALS From January 2001 to October 2003, it was completed at the ICU of Children' s Hospital, Chongqing Medical University. Thirty male rats were selected and divided into sham operation group, ischemia group and nimodipine treated group randomly, with 10 rats in each group.

METHODS:

In sham operation group, the right common carotid artery was identified by blunt dissection without ligation under anesthesia in rats. In ischemia group, at 30 minutes before cerebral ischemia, 2 mL saline was injected intraperitoneally. In nimodipine treated group, at 30 minutes before cerebral ischemia, 0.2 g/L nimodipine (2 mg/kg) was injected intraperitoneally. In all the three groups, the duration between ischemia and decollation was 120 minutes. Rats were decollated under anesthesia and their brains were taken out to assess the activity of phospholipase A2, the free calcium level in brain cells, the brain water content and the changes in mRNA levels of type Ⅱ phospholipase A2 (secretive phospholipase A2) and type Ⅳ phospholipase A2 (cytoplasmic phospholipase A2) in brain tissue.pholipase A2) and type Ⅱ phospholipase A2 (cytoplasmic phospholipase A2)in brain tissue were measured in rats in all the groups.pholipsse A2 in brain tissue In ischemia group and nimodipine treated group, the activity of phospholipase A2 were higher than that in sham operation group [(57.8 ±7.2),(42.5±6.1), (17.1±5.3)%, P＜ 0.05-0.01], and it was a litter lower in nimodipine brain cells It was higher in nimodipine treated group and ischemia group than that in sham operation group [(775.8±105.5), (497.2±45.9), (103.8±10.3) μmol/L,P ＜ 0.05-0.01], and it was lower in nimodipine group than in ischemia group (P ＜ 0.01).that in sham operation group [(82.9±0.5), (80.0±1.1), (72.1±0.01)%, P ＜ 0.05-0.01], and it was lower in nimodipine treated group than that in ischemia group (Ppase A2 could be detected in brain tissue. And the mRNA level of type Ⅱ phospholipase A2 in brain tissue was very low. At 120 minutes after ischemia, mRNA of type Ⅱ phospholipase A2 was detectable and the expression of type Ⅱ phospholipase A2 was increased. Compared to ischemia group, the expression of type Ⅱ phospholipase A2 was not decreased in nimodipine treated group while the expression of type Ⅱ phospholipase A2 was decreased.

CONCLUSION:

Nimodipine is capable of decreasing the free calcium level in brain cells, the activity of phospholipase A2 in brain tissue and the brain water content after ischemia. However, it cannot significantly inhibit the expressions of type Ⅱ phospholipase A2 and type Ⅱ phospholipase A2 after cerebral ischemia.