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BACKGROUND: Researches suggest that cascade reaction of cysteine protease mediated by caspase-12 can cause apoptosis after cerebral ischemia/reperfusion injury;however, nerve growth factor (NGF) can reduce apoptosis through inhibiting activation of that reaction.OBJECTTVE: To observe the effect of NGF on the expression of caspase-12 in brain tissue of rabbits with cerebral ischemia/reperfusion injury, and elucidate the protective mechanism of NGF on neural apoptosis induced by cerebral ischemia/reperfusion injury.DESIGN: Randomized controlled animal study.SETTING: Department of Image, Second Hospital, Hebei Medical University.MATERIALS: A total of 26 healthy New Zealand rabbits, of clean grade, aged 4.5-5 months, weighing (2.6±0.2) kg, were selected in this study. Reagents: NGF (Xiamen Beida Zhilu Biotechnology Co., Ltd.);caspase-12 (Santa Cruz Biotechnology Company, USA, clone number: SC-12395); caspase-3 (Santa Cruz Biotechnology Company, USA, clone number: SC-7272); biotin-antibody Ⅱ and ABC compound (Wuhan Boster Company); in situ end-labeling (ISEL, Beijing Zhongshan Company).METHODS: The experiment was carried out in the Laboratories of Nerve Molecule Image Science and Neurology of the Second Hospital of Hebei Medical University from May to August 2005. ① All animals were randomly divided into three groups. Ischemia/reperfusion (I/R) group (n=10): Left middle cerebral artery (MCA) was blocked for 2 hours and then blooded for 2 hours in order to establish focal cerebral ischemia/reperfusion models. Sham operation group (n=6): Cork was inserted with 3 cm in depth, and then pulled to common carotid artery. Other procedures were as the same as those in ischemia/reperfusion group.Treatment group (n=10): After modeling, 400 AU (16 μg/L) NGF was inserted into cerebral infarction focus sham operation group and at 3 days after reperfusion in other two groups. In addition, contents of caspase-12 and caspase-3 were measured with immunohistochemical technique; mean absorbency (A value)was compared with image analytic system; apoptosis rate and apoptosis quantity of nerves in ischemia/reperfusion area were detected with flow cytometry and DNA TdT-mediated biotinylated-Dutp nick end lawith q test every two groups.MATN OUTCOME MEASURES: Expressions of caspase-12 and caspase-3 and apoptosis in cerebral ischemia/reperfusion area in the 3 groups.RESULTS: All 26 rabbits were involved in the final analysis. ① Expressions of caspase-12 and caspase-3:Expression of caspase-12 was 0.36±0.02 in I/R group and 0.13±0.03 in treatment group; expression of caspase-3 was 0.49±0.05 and 0.27±0.06, respectively. Both of them were higher than those in sham operation group (0.07±0.02, 0.09±0.03, P ＜ 0.01), and expressions of two proteases were lower in treatment group than those in I/R group (P ＜ 0.01). There were significant differences of expression of caspase between I/R group and treatment group as compared with that in sham operation group; meanwhile, there (20.2±1.3)% in I/R group and (7.7±0.8)% in treatment group; apoptosis quantity was (32.8±2.6), (7.6±1.5)/high sight, respectively. Both of them were higher and more than those in sham operation group [(4.8±0.4)%, (0.7±0.2) /high sight, P ＜ 0.01]. Apoptosis rate and apoptosis quantity were lower and less in treatment group than those in I/R group (P ＜ 0.01). There was significant difference between I/R group and treatment group as compared with sham operation group, and there was significant difference between treatment group and I/R group.CONCLUSTON: NGF can decrease the number of apoptotic cells of the cerebral ischemia/reperfusion and inhibit the caspase cascade reaction induced by caspase-12, which is one of the protective mechanisms of NGF.