FTY720对肾缺血再灌注大鼠脑损伤的保护作用和机制  

Protective effect and mechanism of FTY720 on brain injury in a Rat Model of Renal Ischemia-Reperfusion Injury

作　　者：李婷婷[1] 何冠军[2] 刘亚西 赵蕾 康道林 涂发平[4] Li Ting-ting;He Guan-jun;Liu Ya-xi;Zhao Lei;Kang Dao-lin;Tu Fa-ping(Department of Pharmacy,The Second Affiliated Hospital of North Sichuan Medical College,Nanchong 637100,Sichuan,China;Department of Pharmacy,North Sichuan Medical College,Nanchong 637100,Sichuan,China;Department of Nephrology,The People's Hospital of Gaoping District,Nanchong 637100,Sichuan,China;Department of Anesthesiology,The Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,Sichuan,China)

机构地区：[1]川北医学院第二附属医院药剂科,四川南充637100 [2]川北医学院药学院,四川南充637100 [3]高坪区人民医院肾内科,四川南充637100 [4]川北医学院附属医院麻醉科,四川南充637000

出　　处：《四川生理科学杂志》2021年第11期1849-1854,共6页Sichuan Journal of Physiological Sciences

基　　金：2015年川北医学院校级科研发展计划重点项目(CBY15-A-ZD04)。

摘　　要：目的:通过肾缺血再灌注损伤(RIRI)大鼠模型来探讨FTY720能否对大鼠术后的脑损伤产生保护作用及其机制。方法:将30只SD雄性大鼠随机分为假手术组(Sham组),模型组(RIRI组)和FTY720干预组(FTY720组),每组10只。RIRI组和FTY720组建立RIRI模型,Sham组仅暴露肾蒂,不做缺血处理;再灌注前15min,FTY720组腹腔注射液FTY720(1 mg·kg^(-1)),Sham组和RIRI组腹腔注射等体积生理盐水。术后24h每组随机选取5只大鼠处死,取肾组织和脑组织,HE染色观察肾脏组织和海马组织CA1区的病理改变,TUNEL法测定海马组织CA1区神经细胞的凋亡情况,Western Blot检测海马组织CA1区天冬氨酸特异性半胱氨酸蛋白3(Caspase-3)的表达水平;各组剩余5只大鼠进行Morris水迷宫实验,检测其学习能力和空间记忆能力。结果:与Sham组相比,RIRI组大鼠肾脏组织和海马组织CA1区出现明显病理损伤,海马组织CA1区凋亡细胞数显著增多,Caspase-3表达水平均显著升高,Morris水迷宫实验中大鼠逃避潜伏期显著延长,穿越穿台次数显著减少,差异均有统计学意义(P<0.05);与RIRI组比较,FTY720组大鼠海马组织CA1区病理性评分显著降低,凋亡细胞数显著减少,Caspase-3表达水平均显著降低,在Morris水迷宫实验中,FTY720组大鼠逃避潜伏期显著缩短,平台穿越次数显著增加,差异均有统计学意义(P<0.05)。结论:FTY720能改善RIRI引起的大鼠脑损伤和认知功能障碍,其机制可能与FTY720抑制Caspase-3的表达水平,减少海马组织CA1区神经元细胞凋亡有关。Objective:To investigate the protective effect of FTY720 on postoperative brain injury in rats with renal ischemia reperfusion injury(RIRI)and its mechanism.Methods:thirty MALE SD rats were randomly divided into Sham operation group(Sham group),model group(RIRI group)and FTY720 intervention group(FTY720 group),with 10 rats in each group.RIRI group and FTY720 group established RIRI model,while Sham group only exposed renal pedicle without ischemia treatment.15min before reperfusion,FTY720 group was injected intraperitoneally with FTY720(1 mg/kg),Sham group and RIRI group were injected intraperitoneally with equal volume of normal saline.Five rats in each group were randomly selected and sacrificed 24h after the operation.Kidney and brain tissues were collected and pathological changes of kidney and hippocampal CA1 tissues were observed by HE staining.Apoptosis of nerve cells in hippocampal CA1 region was determined by TUNEL method.Western Blot was used to detect the expression of Caspase-3 in CA1 region of hippocampus tissues.Morris water maze test was performed on the remaining 5 rats in each group to test their learning ability and spatial memory ability.Results:Compared with Sham group,RIRI group showed significant pathological damage in renal tissue and hippocampal tissue CA1 region,the number of apoptotic cells in the hippocampal tissue CA1 region was significantly increased,and the expression level of Caspase-3 was significantly increased.The escape latency of rats in Morris water maze test was significantly prolonged,and The Times of crossing the stage were significantly reduced.The differences were statistically significant(P<0.05).Compared with RIRI group,pathological score,apoptotic cell number and caspase-3 expression level of FTY720 group were significantly decreased in CA1 area of hippocampus.In Morris water maze test,escape latency of FTY720 group was significantly shortened and platform crossing times were significantly increased.The differences were statistically significant(P<0.05).Conclusion:FTY7

关 键 词：FTY720 肾缺血再灌注损伤 认知功能障碍 天冬氨酸特异性半胱氨酸蛋白酶3 

分 类 号：R96[医药卫生—药理学]