Kappa阿片受体激动剂salvinorin A调节血管内皮生长因子减轻大鼠前脑缺血后脑水肿的研究

Study on alleviating forebrain ischemia-induced brain edema of rats by kappa-opioid receptor agonist salvinorin A via regulation of vascular endothelial growth factor

目的探讨kappa阿片受体(KOR)激动剂salvinorin A(SA)对前脑缺血再灌注(I/R)损伤大鼠脑水肿和神经功能的改善作用及机制。方法成年雄性SD大鼠经夹闭颈动脉联合低血压建立前脑I/R损伤模型,并根据不同处理方式分为I/R组、I/R+DMSO组、I/R+SA组和I/R+SA+nor BIN(KOR拮抗剂),另设立假手术组。采用Western blotting和免疫组织化学方法检测各组大鼠脑组织血管内皮生长因子(VEGF)蛋白表达;评估脑水肿情况;I/R后1、2、5 d对各组大鼠神经功能进行评定。结果前脑I/R损伤后,I/R组和I/R+DMSO组脑水含量显著高于假手术组(P<0.05),I/R+SA组脑水含量显著低于I/R组(P<0.05),I/R+SA+nor-BIN组脑水量显著高于I/R+SA组(P<0.05)。脑组织VEGF蛋白表达检测结果显示:I/R+SA组显著高于I/R组(P<0.01),I/R+SA+nor-BIN组显著低于I/R+SA组(P<0.05)。I/R+SA组I/R损伤后1、2、5 d神经运动功能评分均显著高于I/R组、I/R+DMSO组和I/R+SA+nor BIN(P<0.05)。结论 SA可以减轻I/R损伤造成的脑组织水肿并改善神经功能,其机制可能与通过KOR上调VEGF蛋白表达有关。

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（P0.05）;the brain water content of I/R ＋ SA group was significantly lower than that of I/R group（P0.05）;and the brain water content of I/R ＋ SA ＋ nor-BIN group was significantly higher than that of I/R ＋ SA group（P0.05）.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（P0.05）.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.