中国医药
中國醫藥
중국의약
CHINA MEDICINE
2013年
8期
1095-1098
,共4页
KATP通道%二氮嗪%缺氧缺血性脑损伤%新生鼠
KATP通道%二氮嗪%缺氧缺血性腦損傷%新生鼠
KATP통도%이담진%결양결혈성뇌손상%신생서
ATP-sensitive K+ channel%Diazoxide%Hypoxia-ischemic brain injury%Newborn rats
目的 探讨ATP敏感性钾通道(KATP通道)开放剂二氮嗪对宫内窒息所致新生大鼠缺氧缺血性脑损伤不同脑区的神经保护作用.方法 采用夹闭妊娠21 d的SD大鼠子宫动静脉方法制作宫内窒息模型,仅分离而不夹闭子宫动静脉剖宫产新生鼠为对照组,夹闭孕鼠子宫动静脉剖宫产新生鼠采用随机数字法随机分为窒息组、二氮嗪组、二氮嗪+格列苯脲组及溶剂组,每组16只.窒息组和对照组不予以药物干预,其余各组分别在宫内窒息后并行剖宫产后0、12、24h腹腔内注射相应干预药物.新生鼠生后72 h处死,以2,3,5-氯化三苯基四氮唑染色方法检测脑梗死面积,以HE染色方法观察皮质、海马、小脑、丘脑和脑干的组织病理学变化并计算脑损伤梯度评分,以反转录-聚合酶链反应方法检测不同脑区KATP通道亚单位mRNA表达量.结果 窒息组脑梗死面积(51.7±10.4)％与对照组(0.3±0.1)％、二氮嗪组(17.0±2.7)％与窒息组(51.7±10.4)％、二氮嗪+格列苯脲组(31.0±8.5)％与二氮嗪组(17.0±20.7)％比较差异均有统计学意义(P＜0.05),窒息组脑梗死面积大,经二氮嗪干预后脑梗死面积减小；窒息组内五部分脑区神经细胞损伤梯度评分差异有统计学意义(P＜0.05),其中海马(4.60±0.52)和皮质(4.50±0.53)损伤最严重,其次是小脑(4.20±0.63)；表达量海马和皮质,Kir6.2mRNA在二氮嗪组(2.56 ±0.88、2.48±0.41)与对照组(3.27±0.38、3.06±0.81)比较差异无统计学意义(P＞0.05).结论 新生SD大鼠宫内窒息后海马和皮质损伤最严重,其次是小脑,最后是丘脑和脑干.二氮嗪对五个脑区均有神经保护作用,且对损伤最严重脑区海马及皮质的神经保护作用最强.
目的 探討ATP敏感性鉀通道(KATP通道)開放劑二氮嗪對宮內窒息所緻新生大鼠缺氧缺血性腦損傷不同腦區的神經保護作用.方法 採用夾閉妊娠21 d的SD大鼠子宮動靜脈方法製作宮內窒息模型,僅分離而不夾閉子宮動靜脈剖宮產新生鼠為對照組,夾閉孕鼠子宮動靜脈剖宮產新生鼠採用隨機數字法隨機分為窒息組、二氮嗪組、二氮嗪+格列苯脲組及溶劑組,每組16隻.窒息組和對照組不予以藥物榦預,其餘各組分彆在宮內窒息後併行剖宮產後0、12、24h腹腔內註射相應榦預藥物.新生鼠生後72 h處死,以2,3,5-氯化三苯基四氮唑染色方法檢測腦梗死麵積,以HE染色方法觀察皮質、海馬、小腦、丘腦和腦榦的組織病理學變化併計算腦損傷梯度評分,以反轉錄-聚閤酶鏈反應方法檢測不同腦區KATP通道亞單位mRNA錶達量.結果 窒息組腦梗死麵積(51.7±10.4)％與對照組(0.3±0.1)％、二氮嗪組(17.0±2.7)％與窒息組(51.7±10.4)％、二氮嗪+格列苯脲組(31.0±8.5)％與二氮嗪組(17.0±20.7)％比較差異均有統計學意義(P＜0.05),窒息組腦梗死麵積大,經二氮嗪榦預後腦梗死麵積減小；窒息組內五部分腦區神經細胞損傷梯度評分差異有統計學意義(P＜0.05),其中海馬(4.60±0.52)和皮質(4.50±0.53)損傷最嚴重,其次是小腦(4.20±0.63)；錶達量海馬和皮質,Kir6.2mRNA在二氮嗪組(2.56 ±0.88、2.48±0.41)與對照組(3.27±0.38、3.06±0.81)比較差異無統計學意義(P＞0.05).結論 新生SD大鼠宮內窒息後海馬和皮質損傷最嚴重,其次是小腦,最後是丘腦和腦榦.二氮嗪對五箇腦區均有神經保護作用,且對損傷最嚴重腦區海馬及皮質的神經保護作用最彊.
목적 탐토ATP민감성갑통도(KATP통도)개방제이담진대궁내질식소치신생대서결양결혈성뇌손상불동뇌구적신경보호작용.방법 채용협폐임신21 d적SD대서자궁동정맥방법제작궁내질식모형,부분리이불협폐자궁동정맥부궁산신생서위대조조,협폐잉서자궁동정맥부궁산신생서채용수궤수자법수궤분위질식조、이담진조、이담진+격렬분뇨조급용제조,매조16지.질식조화대조조불여이약물간예,기여각조분별재궁내질식후병행부궁산후0、12、24h복강내주사상응간예약물.신생서생후72 h처사,이2,3,5-록화삼분기사담서염색방법검측뇌경사면적,이HE염색방법관찰피질、해마、소뇌、구뇌화뇌간적조직병이학변화병계산뇌손상제도평분,이반전록-취합매련반응방법검측불동뇌구KATP통도아단위mRNA표체량.결과 질식조뇌경사면적(51.7±10.4)％여대조조(0.3±0.1)％、이담진조(17.0±2.7)％여질식조(51.7±10.4)％、이담진+격렬분뇨조(31.0±8.5)％여이담진조(17.0±20.7)％비교차이균유통계학의의(P＜0.05),질식조뇌경사면적대,경이담진간예후뇌경사면적감소；질식조내오부분뇌구신경세포손상제도평분차이유통계학의의(P＜0.05),기중해마(4.60±0.52)화피질(4.50±0.53)손상최엄중,기차시소뇌(4.20±0.63)；표체량해마화피질,Kir6.2mRNA재이담진조(2.56 ±0.88、2.48±0.41)여대조조(3.27±0.38、3.06±0.81)비교차이무통계학의의(P＞0.05).결론 신생SD대서궁내질식후해마화피질손상최엄중,기차시소뇌,최후시구뇌화뇌간.이담진대오개뇌구균유신경보호작용,차대손상최엄중뇌구해마급피질적신경보호작용최강.
Objective To investigate the protective effects of diazoxide,a KATP channel opener,on different brain regions of neonatal rats with hypoxic-ischemic brain damage (HIBD) induced by intrauterine asphyxia.Methods The intrauterine asphyxia model was performed by clamping the uterine veins and arteries of the pregnant rats at the 21st day of gestation and the pups were bom by cesarean section.They were randomly divided into four groups:hypoxia-ischemia (HI) group,diazoxide (Dia) group,diazoxide + glibenclamide (Dia + Gli) group and solvent (NaOH) group.The neonatal rats in control group were born after the uterine vessels of the pregnant rats were isolated but not clamped.No drugs were used in HI and control group; otherwise,the intervention medicine was injected intraperitoneally at 0 h,12 h and 24 h after birth in other three groups.The neonatal rats were sacrificed 72 h after birth.The cerebral infarction areas were measured by TTC staining,the histopathologic scores were calculated after HE staining in cortex,hippocampus,cerebellum,thalamus and brainstem and the mRNA of the subunits of the KATP channel were detected by RT-PCR in different brain regions.Results The differences of the cerebral infarction areas between the HI group and control group,Dia group and HI group and Dia + Gli group and Dia group were significant (P ＜0.05).The infarction areas in HI group were high and those were decreased after the treatment of Diazoxide.The histopathologic scores were significantly different among the five brain regions in HI group (P ＜ 0.05):hippocampus (4.60 ± 0.52) and cortex (4.50 ± 0.53) were the most serious injured regions,the next was cerebellum (4.20 ± 0.63).In hippocampus and cortex,the light density of Kir6.2 mRNA in Dia group(2.56 ± 0.88 and 2.48 ± 0.41) had no significant difference compared with that in control group(3.27 ± 0.38 and 3.06 ± 0.81).Conclusions Hippocampus and cortex are the most seriously injured regions after HIBD induced by intrauterine asphyxia in neonatal rats.Diazoxide,a KATP channel opener,has neuroprotective effect on the five brain regions,especially on the hippocampus and cortex.
