Bosentan reduces neuronal apoptosis following spinal cord ischemic reperfusion injury

Abstract

Experimental study. To investigate the effects of endothelin-receptor antagonist Bosentan on the spinal neural apoptosis in rats with ischemic reperfusion (IR) injury. Department of Neurosurgery, the Second Affiliated Hospital, Xi'an Jiaotong University School of Medcine, Xi'an, Shaanxi Province, China: 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. 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. These results suggest Bosentan decreases apoptosis rate after IR injury in the spinal cord, possibly through the ET-1-ETRB signaling pathway.