[1]艾　玲,乔　琼,陈　楠,等.二氢辣椒碱诱导治疗性低体温对小鼠脑缺血再灌注损伤后的脑保护作用[J].新乡医学院学报,2017,34(12):1058-1062.[doi:10.7683/xxyxyxb.2017.12.004]
　AI Ling,QIAO Qiong,CHEN Nan,et al.Neuroprotective effect of therapeutic hypothermia induced by dihydrocapsaicin on cerebral ischemia reperfusion injury in mice[J].Journal of Xinxiang Medical University,2017,34(12):1058-1062.[doi:10.7683/xxyxyxb.2017.12.004]
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二氢辣椒碱诱导治疗性低体温对小鼠脑缺血再灌注损伤后的脑保护作用
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
34
期数:
2017年12
页码:
1058-1062
栏目:
基础研究
出版日期:
2017-12-05

文章信息/Info

Title:
Neuroprotective effect of therapeutic hypothermia induced by dihydrocapsaicin on cerebral ischemia reperfusion injury in mice
作者:
艾　玲1; 乔　琼1; 陈　楠1; 杨　涛1; 唐夏楠1; 岳　静2
（1.华中科技大学同济医学院附属同济医院麻醉科，湖北　武汉　430030；2.华中科技大学同济医学院附属同济医院生殖医学中心，湖北　武汉　430030）
Author(s):
AI Ling1; QIAO Qiong1; CHEN Nan1; YANG Tao1; TANG Xia-nan1; YUE Jing2
（1.Department of Anesthesiology，Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology，Wuhan 430030，Hubei Province，China；2.Reproductive Medical Center，Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology，Wuhan 430030，Hubei Province，China）
关键词:
瞬时感受器电位香草酸受体1; 二氢辣椒碱; 缺血再灌注损伤; 治疗性低体温; 脑保护
Keywords:
transient receptor potential vanilloid 1; dihydrocapsaicin; ischemia reperfusion injury; therapeutic hypothermia; neuroprotection
分类号:
R743.3
DOI:
10.7683/xxyxyxb.2017.12.004
文献标志码:
A
摘要:
目的　探讨二氢辣椒碱（DHC）诱导治疗性低体温对小鼠脑缺血再灌注损伤后的脑保护作用及其机制。方法　将20只成年野生型（WT）小鼠随机分为WT组和WT+DHC组，每组10只；20只瞬时感受器电位香草酸受体1基因敲除（TRPV1 KO）小鼠随机分为TRPV1 KO组和TRPV1 KO+DHC组，每组10只。所有小鼠建立局灶性脑缺血再灌注损伤模型。WT组和TRPV1 KO组小鼠再灌注开始后皮下泵注生理盐水1.25 mg·kg-1·h-1，WT+DHC组和TRPV1 KO+DHC组小鼠再灌注开始后皮下泵注DHC 1.25 mg·kg-1·h-1。所有小鼠再灌注90 min后全部移入 22 ℃的鼠笼中，每隔5 min记录小鼠再灌注期的中心体温变化至再灌注后24 h。在麻醉开始前和再灌注后24 h对小鼠进行神经行为测试评分，测试结束后取小鼠脑组织切片行氯化三苯基四氮唑染色，计算小鼠的脑组织梗死率。结果　4组小鼠再灌注0、30、60 min时中心体温比较差异均无统计学意义（P>0.05）。WT组、TRPV1 KO组和TRPV1 KO+DHC组小鼠再灌注90 min时的中心体温与0、30、60 min时比较差异均无统计学意义（P>0.05），2、3、4、6、12、24 h 时的中心体温与0、30、60、90 min时比较均显著降低（P<0.05）；WT组、TRPV1 KO组和TRPV1 KO+DHC组小鼠2、3、4、6、12、24 h时的中心体温在3组同时间点之间两两比较及组内不同时间点之间两两比较差异均无统计学意义（P>0.05）。WT+DHC组小鼠再灌注后90 min及2、3、4、6、12、24 h时的中心体温与0、30、60 min时比较均显著降低（P<0.05），且均显著低于WT组、TRPV1 KO组和TRPV1 KO+DHC组同时间点（P<0.05）。麻醉前4组小鼠神经行为学测试总分比较差异均无统计学意义（P>0.05）。再灌注后24 h 4组小鼠神经行为学测试总分均低于麻醉前（P<0.05），但WT+DHC组小鼠的行为学测试总分明显高于WT组、TRPV1 KO组和TRPV1 KO+DHC组（P<0.05），而WT组、TRPV1 KO组和TRPV1 KO+DHC组小鼠的行为学测试总分比较差异均无统计学意义（P>0.05）。再灌注后24 h，4组小鼠的自发性活动、攀爬实验、本体觉实验和对触摸触须的反应等4项神经行为学测试评分比较差异均无统计学意义（P>0.05）；WT+DHC组小鼠的四肢运动对称性试验和前爪伸展试验评分显著高于WT组、TRPV1 KO组和TRPV1 KO+DHC组小鼠（P<0.05）；WT组、TRPV1 KO组和TRPV1 KO+DHC组小鼠的四肢运动对称性试验和前爪伸展试验评分比较差异均无统计学意义（P>0.05）。再灌注后24 h，WT+DHC组小鼠的脑组织梗死率显著低于其他3组（P<0.05）；而WT组、TRPV1 KO组、TRPV1 KO+DHC组小鼠脑组织梗死率比较差异均无统计学意义（P>0.05）。结论　小鼠局灶性脑缺血再灌注后皮下泵注DHC可通过激活TRPV1受体诱导治疗性低体温，并减少脑组织损伤，改善脑神经功能。
Abstract:
Objective　To investigate the neuroprotective effect and its mechanism of therapeutic hypothermia induced by dihydrocapsaicin （DHC） on cerebral ischemia reperfusion injury in mice.Methods　Twenty adult wild type （WT） mice were randomly divided into WT group and WT+DHC group，ten mice in each group.Twenty transient receptor potential receptor 1 （TRPV1） knockout mice were randomly divided into TRPV1 KO group and TRPV1 KO+DHC group，ten mice in each group.The model of focal cerebral ischemia reperfusion injury was established in all mice.The mice in the WT group and TRPV1 KO group were subcutaneously injected with physiological saline 1.25 mg·kg-1·h-1 after reperfusion.The mice in the WT+DHC group and TRPV1 KO+DHC group were subcutaneously injected with DHC 1.25 mg·kg-1·h-1 after reperfusion.All the mice were moved into the cage at 22 degrees centigrade after 90 minutes of reperfusion.The core body temperature during the reperfusion period was recorded in every 5 minutes to 24 hours after reperfusion.The neurobehavioral score was performed before anesthesia and 24 hours after anesthesia.After the neurobehavioral test，the brain tissue sections of mice were stained with 2，3，5-triphenyltetrazolium chloride；and the infarction rate of the brain tissue was calculated.Results　There was no significant difference in the core body temperature among the four groups at 0，30 and 60 minutes after reperfusion （P>0.05）.There was no significant difference in the core body temperature between 90 minutes and 0，30 and 60 minutes after reperfusion （P>0.05）；but the core body temperature at 2，3，4，6，12 and 24 hours after reperfusion was significantly lower than that at 0，30，60 and 90 minutes after reperfusion in WT group，TRPV1 KO group and TRPV1 KO+DHC group（P<0.05）.There was no significant difference in the core body temperature among the WT group，TRPV1 KO group and TRPV1 KO+DHC group at 2，3，4，6，12 and 24 hours after reperfusion （P>0.05）.The core body temperature at 90 minutes and 2，3，4，6，12，24 hours after reperfusion was significantly lower than that at 0，30 and 60 minutes after reperfusion in WT+DHC group（P<0.05）；and the core body temperature in WT+DHC group was significantly lower than that in WT group，TRPV1 KO group and TRPV1 KO+DHC group at the same time point（P<0.05）.There was no significant difference in the total neurobehavioral score among the four groups before anesthesia （P>0.05）.The total neurobehavioral score at 24 hours after reperfusion was significantly lower than that before anesthesia in the four groups （P<0.05）.The total neurobehavioral score in WT+DHC group was significantly higher than that in WT group，TRPV1 KO group and TRPV1 KO+DHC group at 24 hours after reperfusion（P<0.05）.There was no significant difference in the total neurobehavioral score among WT group，TRPV1 KO group and TRPV1 KO+DHC group at 24 hours after reperfusion （P>0.05）.There was no significant difference in the score of spontaneous activity，climbing test，body proprioception and response to vibrissae touch among the four groups at 24 hours after reperfusion （P>0.05）.The score of symmetry test of limbs movement and forepaw stretching test in WT+DHC group was significantly higher than that in WT group，TRPV1 KO group and TRPV1 KO+DHC group at 24 hours after reperfusion（P<0.05）.There was no significant difference in the score of symmetry test of limbs movement and forepaw stretching test among the WT group，TRPV1 KO group and TRPV1 KO+DHC group at 24 hours after reperfusion （P>0.05）.The infarction rate of brain tissue in WT+DHC group was significantly lower than that in the other three groups at 24 hours after reperfusion （P<0.05）；but there was no significant difference in the infarction rate of brain tissue among the WT group，TRPV1 KO group and TRPV1 KO+DHC group（P>0.05）.Conclusion　Subcutaneous injection of DHC after focal cerebral ischemia and reperfusion of mice can induce therapeutic hypothermia by activating TRPV1 receptor，and reduce brain tissue damage and improve neurological function.

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更新日期/Last Update: 2017-12-05