Bosentan reduces neuronal apoptosis following spinal cord ischemic reperfusion injury.

STUDY DESIGN: Experimental study.

OBJECTIVES: To investigate the effects of endothelin-receptor antagonist Bosentan on the spinal neural apoptosis in rats with ischemic reperfusion (IR) injury.

SETTING: Department of Neurosurgery, the Second Affiliated Hospital, Xi'an Jiaotong University School of Medcine, Xi'an, Shaanxi Province, China:

METHODS: Sprague-Dawley Rats were randomly divided into two groups, saline (IRS, n=48) and Bosentan (IRB, n=48) treatment, respectively, when reperfused in 6 h, 12 h, 24 h, 3 days, 5 days and 7 days. Immunohistochemical staining was used to assess endothelin-1 (ET-1), endothelin receptor type A (ETRA), endothelin receptor type B (ETRB), Bcl-2, Bax, Caspase-8, Caspase-9 and Caspase-3 expression. ET-1 and its receptor in spinal cord tissue were evaluated by real-time PCR. Plasma ET-1 concentration was also detected using radioimmunoassay.

RESULTS: Compared with the group IRS, plasma concentration of ET-1 in group IRB was significantly increased at each time point (P<0.05) and peaked at 24 h (P<0.01). ETRB expression in group IRB was significantly higher than group IRS at each time point (P<0.05) and peaked at day 3 (P<0.01). The difference in the expression of ETRA was not statistically significant in the group IRS and IRB (P>0.05). The apoptosis rate in group IRB was significantly decreased at each time point (P<0.05). The protein expressions of Bcl-2, Bax, Caspase-8, Caspase-9 and Caspase-3 were significantly increased in response to Bosentan treatment after IR.

CONCLUSION: These results suggest Bosentan decreases apoptosis rate after IR injury in the spinal cord, possibly through the ET-1-ETRB signaling pathway.