吸入外源性硫化氢对大鼠脑缺血-再灌注后脑水肿的影响及机制  

Effects of exogenous hydrogen sulfide inhalation on brain edema induced by experimental stroke in rats and mechanism study

作　　者：程龙[1] 李航兵[1] 尹金玲[1] 赵夏洁 魏霞[1] 张兵[1] 

机构地区：[1]哈尔滨医科大学附属第二医院麻醉科黑龙江省麻醉与危重病学重点实验室黑龙江省高校麻醉基础理论与应用研究重点实验室,150086

出　　处：《实用医学杂志》2016年第14期2291-2294,共4页The Journal of Practical Medicine

基　　金：国家自然科学基金资助项目(编号:81372026;81000822)

摘　　要：目的：评价吸入外源性硫化氢对大鼠脑缺血-再灌注后脑水肿的作用,并探讨其机制。方法：健康雄性SD大鼠72只,体质量220-250 g,采用随机数字表法,将其分为6组（n=12）：假手术组（Sham）、脑缺血-再灌组（I/R）、硫化氢40 ppm组（H2S（40））、硫化氢80 ppm组（H2S（80））、脑室内注射PBS组（IC（PBS））和脑室内注射磷酸激酶C（PKC）抑制剂组（IC（PKCi））。H2S（40）和H2S（80）组在再灌注开始时分别吸入40和80 ppm硫化氢3 h。IC（PBS）和IC（PKCi）组预先经脑室内注射5μL的PBS或PKC抑制剂Go6983,再灌注时吸入40 ppm硫化氢3 h。再灌注24 h进行神经功能学评分,脑水肿程度和梗死面积测定,并采用Western法测定水通道蛋白4（AOP4）的表达。结果：与Sham组相比,I/R组Garcia评分明显降低,剔除胶带所需时间明显延长：脑肿胀和梗死面积明显增加,AOP4蛋白表达上调（P〈0.05）。与I/R组相比,吸入硫化氢组显著改善神经功能评分,减轻脑肿胀和梗死,下调AOP4的表达（P〈0.05）。IC（PKCi）可减弱硫化氢对脑的保护作用。结论：吸入40或80 ppm的硫化氢减轻大鼠脑缺血-再灌注引起的神经功能障碍,减少梗死面积,减轻脑水肿,其机制可能与硫化氢通过调节PKC下调AQP4的表达有关。Objective To investigate the effects of exogenous H2S gas on brain edema induced by experimental stroke and underlying mechanisms.Methods Rats were divided into 6 groups,shame,I/R,H2S（40）,H2S（80）,IC（PBS） and IC（PKCi）.Rats of H2S（40） and H2S（80） groups underwent 2h MCAO and received 40 ppm or 80 ppm H2S inhalation for 3 h at the beginning of reperfusion.Rats of IC（PBS） and IC（PKCi） were injected with 5 μL PBS or PKC inhibitor Go6983 first and received 40 ppm for 3 h.The effects of H2S were investigated by evaluating neurological function,infarct size,and brain edema volume.Western blot was used to measure AQP4 protein expression at24 h after reperfusion.PKC inhibitor Go6983 was injected into intracerebral ventricular to explore the possible mechanisms for the neuroprotective effects of H2S.Results 40 and 80 ppm H2S inhalation significantly reduced neurological deficits,infarct size,and brain edema volume after MCA0（P 〈0.05）.The expression of AQP4 in the peri-infarct area of brain was also inhibited after inhalation of H2S（P 〈0.05）.The PKC inhibitor reversed the neuroprotection of H2S with an increased AQP4 expression at the same time（P 〈0.05）.Conclusion 40 or80 ppm H2S inhalation attenuated brain edema,reduced infarct volume and improved neurologic function in a rat experimental stroke model.The therapeutic benefits of H2S inhalation might be caused by downregulation of AQP4 expression under possible regulation of PKC.

关 键 词：硫化氢 大脑中动脉阻塞 脑水肿 水通道蛋白4 磷酸激酶C 

分 类 号：R614[医药卫生—麻醉学]