Effect of DADLE on expressions of Bax and Bcl-2 proteins in rats with acute cerebral ischemia repeffusion

Abstract

Objective To observe the expressions of Bax and Bcl-2 proteins in the brain tissue of the rats with acute cerebral ischemia reperfusion, and to explore the effect of DADLE, a delta opioid receptor ago- nist, on brain apoptotic pathways of acute cerebral ischemia reperfusion and the role of DADLE in the protection of brain. Methods 50 healthy female SD rats（ 180-220 g） were randomly divided into 5 groups： sham operation group （Sham, n = 10）： only exposed blood vessels without clipping; ischemia reperfusion group （I/R, n = 10）： modified two-vessel occlusion with hypotension to establish a model of cerebral ischemia, and reperfused 15 min after ischemia; DADLE treatment group was subdivided into group of 2 mg/kg（A, n = 10）, group of 3mg/kg （B, n= 10）, and group of 5 mg/kg （C, n-- 10）： on the basis of I/R group with reperfusion via external jugular vein injection of DADLE. Expressions of Bax and Bcl-2 proteins were detected by immunohistochemistry assay after the operation. Results The number of cells with Bax or Bcl-2 expression （20.38 ＋ 2.84 and 9.62 ＋ 2.10, P 〈 0.05 ）was significantly smaller in Sham group than in the other groups; In I/R group, the number of cells with Bax or Bcl-2 expression was 52.73 ＋ 6.08 and 19.49 ＋ 2.35 ; In DADLE treatment groups, the number of cells with Bax experssion was 43.71 -＋ 3.85 for group A, 37.92 ＋ 4.08 for group B, and 36.20 -＋ 3.94 for group C; the number of cells with Bel-2 expression was 28.74 _＋ 2.41,33.58 ＋ 2.16,and 34.96 ＋ 1.98, respectively. The ratio of Bel-2/Bax was significantly higher in Sham group than in I/R group （49.3% ＋ 3.4% vs. 35.8% ＋ 3.2%, P〈 0.05 ） ; and it was 66.4% ~ 6.8% in group A, 85.7% ：t 7.3% in group B, and 92.6% ＋ 6.9% in group C.Conelusions In rats with acute cerebral ischemia reperfusion injury, expressions of Bax and Bcl-2 proteins are obviously upregulated. DADLE can play a role in protection of brain by affecting the expression degree of Bax and Bcl-2 and thus lowering apoptosis. Bcl-2Bax ratio shows that the role and the dose is in a S-shape curve of dose-effect. Key words: DADLE ; Whole brain ischemia reperfusion; Bax; Bcl-2