Abstract:

Objective  To investigate the effects of kappa-opioid receptor (KOR) agonist, salovinorin A (SA), on alleviating brain edema and neurological function of rats with forebrain ischemia/reperfusion (I/R) injury and relevant mechanisms. Methods  A forebrain I/R injury model was established by colligating the bilateral common carotid arteries of SD rats combined with hypotension. The rats were divided into I/R group, I/R+DMSO group, I/R+SA group, I/R+SA+norBIN (KOR agonist) group, and sham operation group according to different processing methods. The protein expression of VEGF in brain tissues of rats was detected by Western blotting and immunohistochemical method. The brain edema of rats was evaluated. The neurological function of rats was evaluated 1, 2, and 5 d after I/R injury. Results  After forebrain I/R injury, the brain water content of I/R group and I/R+DMSO group was significantly higher than that of sham operation group (P<0.05); the brain water content of I/R+SA group was significantly lower than that of I/R group (P<0.05); and the brain water content of I/R+SA+nor-BIN group was significantly higher than that of I/R+SA group (P<0.05). Detection results of the protein expression of VEGF in brain tissues showed that the protein expression of VEGF of I/R+SA group was significantly higher than that of I/R group (P<0.01) and the protein expression of VEGF of I/R+SA+nor-BIN group was significantly lower than that of I/R+SA group (P<0.05). Scores of neurological motor function of I/R+SA group 1, 2, and 5 d after I/R injury were significantly higher than those of I/R group, I/R+DMSO group, and I/R+SA+norBIN group (P<0.05).  Conclusion  SA can alleviate the brain edema caused by I/R injury and improve the neurological function. The mechanism may be relevant to the up-regulation of the protein expression of VEGF via KOR.

Key words: brain ischemia/reperfusion, cerebral edema, neurologic function, kappa-opioid agonist, vascular endothelial growth factor