[Protective effect of ferulic acid on neuronal apoptosis of spinal cord subsequent to aortic blood cross-clamping in rabbits].
OBJECTIVE
To investigate the protective effect of ferulic acid on neuronal apoptosis of the spinal cord after aortic blood cross-clamping and its mechanism in rabbits.


METHODS
Twenty-four rabbits were randomly divided into sham operation group, ischemia/reperfusion (I/R) injury group and ferulic acid group. Spinal cord I/R injury model was replicated by clamping blood of the infrarenal aorta for 40 minutes followed reperfusion for 7 days. Ferulic acid 50 mg/kg was injected 15 minutes before aortic clamping in ferulic acid group. The aorta was not clamped in sham operation group. Contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in plasma were assayed at 10 minutes before clamping (C-10), before removal of occlusion (C40), at 60 minutes (R60) and on the 7 th day (R7d) after reperfusion. Apoptosis of neurones of spinal cord and the expressions of Bax and Bcl-2 protein were assayed by immunohistochemical technique. Neurologic function score of hind limb was observed after operation.


RESULTS
(1)The activity of MDA after I/R in I/R injury group was increased significantly compared with those before clamping and those in sham operation group (P<0.05 or P<0.01). The activity of MDA in ferulic acid group was significantly higher than that at C-10 (P<0.05), while significantly lower than those in I/R injury group at any time point (P<0.05 or P<0.01), but showed no significant difference compared with sham operation group. Changes in SOD activities were opposite to that of MDA. (2)The expression of Bax protein in I/R injury group was increased significantly (P<0.05), but the expression of Bcl-2 protein was decreased significantly compared with that in sham operation group (P<0.01). In ferulic acid group, the expression of Bax protein was significantly lower than that in I/R injury group and higher than that in sham operation group (P<0.01 and P<0.05), and the expression of Bcl-2 protein was higher than those in I/R injury group and sham operation group (both P<0.01). (3)The index of neuronal apoptosis in I/R injury group was significantly higher than that in sham operation group (P<0.01), and that in ferulic acid group was much lower than that in I/R injury group, but higher than sham operation group (P<0.01 and P<0.05). (4)The degree of paralysis in ferulic acid group was significantly lower than that in I/R injury group, and a higher neurologic score was observed (both P<0.01).


CONCLUSIONS
Ferulic acid can reduce the spinal cord neuronal apoptosis as a result of aortic occlusion in rabbits. The possible mechanism is that it decreases protein expression of Bax, increases that of Bcl-2 and enhances antioxidation.
Ke
Qi-bin
QB
Department of Anesthesiology, Yichang Central People's Hospital, the First Clinical Medical College, China Three Gorges University, Yichang 443003, Wuhan, China.
Jiang
Ya
Y
Huang
Hai-bo
HB
Zhou
Qing-shan
QS
Yu
Qi-jin
QJ
Xiong
Gui-xian
GX
D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery; D017209:Apoptosis / Q000187:drug effects*; D003250:Constriction; D003373:Coumaric Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D020760:Spinal Cord Ischemia / Q000378:metabolism / Q000473:pathology*; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D003373:Coumaric Acids; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; C004999:ferulic acid; D013482:Superoxide Dismutase