中华围产医学杂志
中華圍產醫學雜誌
중화위산의학잡지
CHINESE JOURNAL OF PERINATAL MEDICINE
2014年
2期
114-118
,共5页
刘锟%张桂艳%叶信健%张文娟%马炎旭%胡文弋%高红昌%严志汉
劉錕%張桂豔%葉信健%張文娟%馬炎旭%鬍文弋%高紅昌%嚴誌漢
류곤%장계염%협신건%장문연%마염욱%호문익%고홍창%엄지한
婴儿持续高胰岛素血症性低血糖症%脑疾病%疾病模型,动物%预后
嬰兒持續高胰島素血癥性低血糖癥%腦疾病%疾病模型,動物%預後
영인지속고이도소혈증성저혈당증%뇌질병%질병모형,동물%예후
Persistent hyperinsulinemia hypoglycemia of infancy%Brain diseases%Disease models,animal%Prognosis
目的 研究模拟早产儿反复严重新生期低血糖大鼠模型的制作方法,并观察其脑损伤及预后情况. 方法 24只2日龄Sprague-Dawley大鼠随机分为新生期低血糖组、新生期对照组、青春期随访组和青春期对照组,每组6只.研究组(包括新生期低血糖组及青春期随访组)大鼠在生后第2、4、6天腹腔注射胰岛素40 U/kg诱导严重低血糖(血糖≤1.4 mmol/L),对照组(包括新生期对照组和青春期对照组)予等量生理盐水.对各组大鼠的海马和枕叶皮层行原位末端转移酶标记技术染色,观察反复严重新生期低血糖后新生期及青春期不同部位脑细胞的损伤情况.采用方差分析和t检验进行统计学处理. 结果 在生后第2、4、6天,研究组新生大鼠在给予胰岛素后2.5 h均达到严重低血糖水平(生后第2天＜1.3 mmol/L,生后第4、6天均＜1.4 mmol/L).与新生期对照组相比,新生期低血糖组海马CAI、CA3、DG区和枕叶皮层内损伤神经元个数增多[新生期低血糖组分别为(23±5)、(28±5)、(234±26)和(187±17)个,新生期对照组分别为(14±3)、(16±3)、(26±4)和(30±6)个,t值分别为2.97、3.11、4.08和3.52,P值均＜0.05],损伤指数升高(新生期低血糖组分别为0.22±0.04、0.24±0.06、0.83±0.06和0.34±0.08,新生期对照组分别为0.12±0.02、0.13±0.02、0.16±0.03和0.17±0.04,t值分别为3.42、3.68、3.92和2.76,P值均＜0.05).与青春期对照组相比,青春期随访组上述脑区损伤神经元亦增多[青春期随访组分别为(54±7)、(42±9)、(296±34)和(75±12)个,青春期对照组分别为(19±3)、(16±2)、(31±5)和(20±4)个,t值分别为3.47、3.24、3.80和3.92,P值均＜0.05],损伤指数亦升高(青春期随访组分别为0.86±0.12、0.89±0.14、0.92±0.09和0.54±0.11,青春期对照组分别为0.14±0.03、0.13±0.02、0.17±0.02和0.15±0.04,t值分别为3.05、3 60、3.52和3.33,P值均＜0.05).结论 生后第2、4、6天腹腔注射40 U/kg胰岛素,可成功建立模拟早产儿反复严重新生期低血糖的大鼠模型.反复严重新生期低血糖可引起大鼠海马和枕叶损伤,且损伤持续存在.
目的 研究模擬早產兒反複嚴重新生期低血糖大鼠模型的製作方法,併觀察其腦損傷及預後情況. 方法 24隻2日齡Sprague-Dawley大鼠隨機分為新生期低血糖組、新生期對照組、青春期隨訪組和青春期對照組,每組6隻.研究組(包括新生期低血糖組及青春期隨訪組)大鼠在生後第2、4、6天腹腔註射胰島素40 U/kg誘導嚴重低血糖(血糖≤1.4 mmol/L),對照組(包括新生期對照組和青春期對照組)予等量生理鹽水.對各組大鼠的海馬和枕葉皮層行原位末耑轉移酶標記技術染色,觀察反複嚴重新生期低血糖後新生期及青春期不同部位腦細胞的損傷情況.採用方差分析和t檢驗進行統計學處理. 結果 在生後第2、4、6天,研究組新生大鼠在給予胰島素後2.5 h均達到嚴重低血糖水平(生後第2天＜1.3 mmol/L,生後第4、6天均＜1.4 mmol/L).與新生期對照組相比,新生期低血糖組海馬CAI、CA3、DG區和枕葉皮層內損傷神經元箇數增多[新生期低血糖組分彆為(23±5)、(28±5)、(234±26)和(187±17)箇,新生期對照組分彆為(14±3)、(16±3)、(26±4)和(30±6)箇,t值分彆為2.97、3.11、4.08和3.52,P值均＜0.05],損傷指數升高(新生期低血糖組分彆為0.22±0.04、0.24±0.06、0.83±0.06和0.34±0.08,新生期對照組分彆為0.12±0.02、0.13±0.02、0.16±0.03和0.17±0.04,t值分彆為3.42、3.68、3.92和2.76,P值均＜0.05).與青春期對照組相比,青春期隨訪組上述腦區損傷神經元亦增多[青春期隨訪組分彆為(54±7)、(42±9)、(296±34)和(75±12)箇,青春期對照組分彆為(19±3)、(16±2)、(31±5)和(20±4)箇,t值分彆為3.47、3.24、3.80和3.92,P值均＜0.05],損傷指數亦升高(青春期隨訪組分彆為0.86±0.12、0.89±0.14、0.92±0.09和0.54±0.11,青春期對照組分彆為0.14±0.03、0.13±0.02、0.17±0.02和0.15±0.04,t值分彆為3.05、3 60、3.52和3.33,P值均＜0.05).結論 生後第2、4、6天腹腔註射40 U/kg胰島素,可成功建立模擬早產兒反複嚴重新生期低血糖的大鼠模型.反複嚴重新生期低血糖可引起大鼠海馬和枕葉損傷,且損傷持續存在.
목적 연구모의조산인반복엄중신생기저혈당대서모형적제작방법,병관찰기뇌손상급예후정황. 방법 24지2일령Sprague-Dawley대서수궤분위신생기저혈당조、신생기대조조、청춘기수방조화청춘기대조조,매조6지.연구조(포괄신생기저혈당조급청춘기수방조)대서재생후제2、4、6천복강주사이도소40 U/kg유도엄중저혈당(혈당≤1.4 mmol/L),대조조(포괄신생기대조조화청춘기대조조)여등량생리염수.대각조대서적해마화침협피층행원위말단전이매표기기술염색,관찰반복엄중신생기저혈당후신생기급청춘기불동부위뇌세포적손상정황.채용방차분석화t검험진행통계학처리. 결과 재생후제2、4、6천,연구조신생대서재급여이도소후2.5 h균체도엄중저혈당수평(생후제2천＜1.3 mmol/L,생후제4、6천균＜1.4 mmol/L).여신생기대조조상비,신생기저혈당조해마CAI、CA3、DG구화침협피층내손상신경원개수증다[신생기저혈당조분별위(23±5)、(28±5)、(234±26)화(187±17)개,신생기대조조분별위(14±3)、(16±3)、(26±4)화(30±6)개,t치분별위2.97、3.11、4.08화3.52,P치균＜0.05],손상지수승고(신생기저혈당조분별위0.22±0.04、0.24±0.06、0.83±0.06화0.34±0.08,신생기대조조분별위0.12±0.02、0.13±0.02、0.16±0.03화0.17±0.04,t치분별위3.42、3.68、3.92화2.76,P치균＜0.05).여청춘기대조조상비,청춘기수방조상술뇌구손상신경원역증다[청춘기수방조분별위(54±7)、(42±9)、(296±34)화(75±12)개,청춘기대조조분별위(19±3)、(16±2)、(31±5)화(20±4)개,t치분별위3.47、3.24、3.80화3.92,P치균＜0.05],손상지수역승고(청춘기수방조분별위0.86±0.12、0.89±0.14、0.92±0.09화0.54±0.11,청춘기대조조분별위0.14±0.03、0.13±0.02、0.17±0.02화0.15±0.04,t치분별위3.05、3 60、3.52화3.33,P치균＜0.05).결론 생후제2、4、6천복강주사40 U/kg이도소,가성공건립모의조산인반복엄중신생기저혈당적대서모형.반복엄중신생기저혈당가인기대서해마화침협손상,차손상지속존재.
Objective To investigate the rat model establishment of repetitive and profound hypoglycemia of neonatal period (RPHN),and understand related brain injury and its prognosis.Methods Twenty-four 2 day-old Sprague-Dawley rats were randomly divided into four groups with six in each:the insulin-treated neonatal rats group (INS-N),control neonatal rats group (CON-N),insulin-treated neonatal rats followed up to adolescent stage group (INS-A) and control neonatal rats followed up to adolescent stage group (CON-A).Rats in INS N group and INS-A group received intraperitoneal injections of insulin (40 U/kg) on postnatal day 2,4 and 6 to induce severe hypoglycemia (≤ 1.4 mmol/L).The rats in corresponding control group received the same amount of saline.Terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling assay (TUNEL) was applied to study the amounts of injured neurons in occipital cortex and hippocampus of the rats in their neonatal period and adolescent period.The difference between the two groups was compared by t test.Results In INS-N and INS-A group,neonatal rats reached severe hypoglycemia level at 2.5 h after insulin injection (glucose at day 2＜1.3 mmol/L,at day 4 and day 6＜1.4 mmol/L).RPHN was observed to induce neuron injury in hippocampus CA1,CA3,DG,and occipital cortex in the INS N group (numbers of neuron injury in INS-N group:23±5,28±5,234±26 and 187± 17,respectively; in CON N group:14±3,16±3,26±4 and 30±6) (t=2.97,3.11,4.08 and 3.52,all P＜0.05).Compared with CON-N group,INS N group had higher injured index in above brain regions (INS-N group:0.22±0.04,0.24±0.06,0.83±0.06 and 0.34±0.08,respectively; CON-N group:0.12±0.02,0.13±0.02,0.16±0.03 and 0.17±0.04) (t=3.42,3.68,3.92 and 2.76,all P＜0.05).When the newborn rats reached their adolescent stage,there were more injured neurons in INS-A group in above brain regions (INS-A group:54± 7,42±9,296±34 and 75± 12,respectively; CON-A group:19±3,16±2,31 ±5 and 20±4) (t=3.47,3.24,3.80 and 3.92,all P＜0.05),and also showed higher injured index (INS-A group:0.86±0.12,0.89±0.14,0.92±0.09and 0.54±0.11,respectively; CON-A group:0.14±0.03,0.13±0.02,0.17±0.02 and 0.15±0.04) (t=3.05,3.60,3.52 and 3.33,all P＜0.05).Conclusion RPHN rat model can be produced by intraperitoneal injection of insulin (40 U/kg) on day 2,4 and 6.RPHN causes neuron injury in the occipital cortex and hippocampus,and such injury may last to adolescent stage.
