中华围产医学杂志
中華圍產醫學雜誌
중화위산의학잡지
CHINESE JOURNAL OF PERINATAL MEDICINE
2012年
11期
689-695
,共7页
王金梅%郑明明%周建军%刁振宇%胡娅莉
王金梅%鄭明明%週建軍%刁振宇%鬍婭莉
왕금매%정명명%주건군%조진우%호아리
先兆子痫%疾病模型,动物%脂多糖类
先兆子癇%疾病模型,動物%脂多糖類
선조자간%질병모형,동물%지다당류
Pre-eclampsia%Disease models,animal%Lipopolysaccharides
目的 在妊娠甲期利用脂多糖建立孕鼠子痫前期模型,为子痫前期发病机制探索奠定基础. 方法 研究第1步是探索脂多糖诱导孕鼠子痫前期模型的合适剂量:24只妊娠大鼠随机分为6组(n=4),其中5组分别于妊娠第5天尾静脉缓慢注射2 ml的脂多糖溶液,其脂多糖剂量分别为0.3、0.5、0.7、1.0、2.0 μg/kg,另1组注射2 ml生理盐水为对照组.采用配对或两独立样本t检验比较各组血压、尿蛋白总量和胎盘病理变化,确定最合适脂多糖造模剂量.第2步是应用所选脂多糖的合适剂量造模.模型组:取19只孕鼠于妊娠第5天尾静脉注射最佳剂量脂多糖,其中15只于妊娠第20天处死取样,另4只喂养至产后第10天.正常妊娠组:取15只孕鼠于妊娠第5天尾静脉缓慢注射生理盐水2 ml.3只交配但未成功受孕的大鼠作为未孕组.采用方差分析及LSD两两检验比较妊娠期及产后血压、尿蛋白总量及胎盘重、胎仔重及病理变化,探讨模型的子痫前期表型特点.结果 第1步研究结果:脂多糖0.3 μg/kg组胎盘重量比对照组增加；0.7、1.0 μg/kg组于妊娠第12天尿蛋白总量达峰值后又下降；脂多糖1.0、2.0 μg/kg组均有1只孕鼠(1/4)于妊娠第16天阴道大量流血死亡；只有脂多糖0.5 μg/kg组血压和尿蛋白总量呈明显上升趋势,且胎仔体重较对照组减低,故选脂多糖0.5 μg/kg作为最佳造模剂量.第2步研究结果:模型组大鼠较正常妊娠组于妊娠第6天始血压增高[(124.89±1.79) mm Hg与(119.02±1.80) mm Hg,LSD检验,P=0.03]、妊娠第9天始尿蛋白总量增加[(2.02±0.29) mg与(1.11±0.18) mg,LSD检验,P=0.00],妊娠第20天吸收胚胎数目增多[3.6％(7/194)与0.0％(0/200),Fisher精确概率法,P=0.01],胎盘出血发生率增高[4.1％(8/194)与0.0％(0/200),Fisher精确概率法,P=0.00],胎儿生长受限发生率增加[13.9％(27/194)与6.0％(12/200),X2=6.92,P=0.01],病理组织学显示胎盘明显炎症细胞浸润,肾小球系膜细胞增多、肾小管上皮细胞肿胀脱落.模型组分娩后第6天血压及尿蛋白总量恢复至基础值,未孕组大鼠血压及尿蛋白总量无改变. 结论 妊娠早期尾静脉注射脂多糖0.5μtg/kg可成功诱导大鼠出现子痫前期表型.
目的 在妊娠甲期利用脂多糖建立孕鼠子癇前期模型,為子癇前期髮病機製探索奠定基礎. 方法 研究第1步是探索脂多糖誘導孕鼠子癇前期模型的閤適劑量:24隻妊娠大鼠隨機分為6組(n=4),其中5組分彆于妊娠第5天尾靜脈緩慢註射2 ml的脂多糖溶液,其脂多糖劑量分彆為0.3、0.5、0.7、1.0、2.0 μg/kg,另1組註射2 ml生理鹽水為對照組.採用配對或兩獨立樣本t檢驗比較各組血壓、尿蛋白總量和胎盤病理變化,確定最閤適脂多糖造模劑量.第2步是應用所選脂多糖的閤適劑量造模.模型組:取19隻孕鼠于妊娠第5天尾靜脈註射最佳劑量脂多糖,其中15隻于妊娠第20天處死取樣,另4隻餵養至產後第10天.正常妊娠組:取15隻孕鼠于妊娠第5天尾靜脈緩慢註射生理鹽水2 ml.3隻交配但未成功受孕的大鼠作為未孕組.採用方差分析及LSD兩兩檢驗比較妊娠期及產後血壓、尿蛋白總量及胎盤重、胎仔重及病理變化,探討模型的子癇前期錶型特點.結果 第1步研究結果:脂多糖0.3 μg/kg組胎盤重量比對照組增加；0.7、1.0 μg/kg組于妊娠第12天尿蛋白總量達峰值後又下降；脂多糖1.0、2.0 μg/kg組均有1隻孕鼠(1/4)于妊娠第16天陰道大量流血死亡；隻有脂多糖0.5 μg/kg組血壓和尿蛋白總量呈明顯上升趨勢,且胎仔體重較對照組減低,故選脂多糖0.5 μg/kg作為最佳造模劑量.第2步研究結果:模型組大鼠較正常妊娠組于妊娠第6天始血壓增高[(124.89±1.79) mm Hg與(119.02±1.80) mm Hg,LSD檢驗,P=0.03]、妊娠第9天始尿蛋白總量增加[(2.02±0.29) mg與(1.11±0.18) mg,LSD檢驗,P=0.00],妊娠第20天吸收胚胎數目增多[3.6％(7/194)與0.0％(0/200),Fisher精確概率法,P=0.01],胎盤齣血髮生率增高[4.1％(8/194)與0.0％(0/200),Fisher精確概率法,P=0.00],胎兒生長受限髮生率增加[13.9％(27/194)與6.0％(12/200),X2=6.92,P=0.01],病理組織學顯示胎盤明顯炎癥細胞浸潤,腎小毬繫膜細胞增多、腎小管上皮細胞腫脹脫落.模型組分娩後第6天血壓及尿蛋白總量恢複至基礎值,未孕組大鼠血壓及尿蛋白總量無改變. 結論 妊娠早期尾靜脈註射脂多糖0.5μtg/kg可成功誘導大鼠齣現子癇前期錶型.
목적 재임신갑기이용지다당건립잉서자간전기모형,위자간전기발병궤제탐색전정기출. 방법 연구제1보시탐색지다당유도잉서자간전기모형적합괄제량:24지임신대서수궤분위6조(n=4),기중5조분별우임신제5천미정맥완만주사2 ml적지다당용액,기지다당제량분별위0.3、0.5、0.7、1.0、2.0 μg/kg,령1조주사2 ml생리염수위대조조.채용배대혹량독립양본t검험비교각조혈압、뇨단백총량화태반병리변화,학정최합괄지다당조모제량.제2보시응용소선지다당적합괄제량조모.모형조:취19지잉서우임신제5천미정맥주사최가제량지다당,기중15지우임신제20천처사취양,령4지위양지산후제10천.정상임신조:취15지잉서우임신제5천미정맥완만주사생리염수2 ml.3지교배단미성공수잉적대서작위미잉조.채용방차분석급LSD량량검험비교임신기급산후혈압、뇨단백총량급태반중、태자중급병리변화,탐토모형적자간전기표형특점.결과 제1보연구결과:지다당0.3 μg/kg조태반중량비대조조증가；0.7、1.0 μg/kg조우임신제12천뇨단백총량체봉치후우하강；지다당1.0、2.0 μg/kg조균유1지잉서(1/4)우임신제16천음도대량류혈사망；지유지다당0.5 μg/kg조혈압화뇨단백총량정명현상승추세,차태자체중교대조조감저,고선지다당0.5 μg/kg작위최가조모제량.제2보연구결과:모형조대서교정상임신조우임신제6천시혈압증고[(124.89±1.79) mm Hg여(119.02±1.80) mm Hg,LSD검험,P=0.03]、임신제9천시뇨단백총량증가[(2.02±0.29) mg여(1.11±0.18) mg,LSD검험,P=0.00],임신제20천흡수배태수목증다[3.6％(7/194)여0.0％(0/200),Fisher정학개솔법,P=0.01],태반출혈발생솔증고[4.1％(8/194)여0.0％(0/200),Fisher정학개솔법,P=0.00],태인생장수한발생솔증가[13.9％(27/194)여6.0％(12/200),X2=6.92,P=0.01],병리조직학현시태반명현염증세포침윤,신소구계막세포증다、신소관상피세포종창탈락.모형조분면후제6천혈압급뇨단백총량회복지기출치,미잉조대서혈압급뇨단백총량무개변. 결론 임신조기미정맥주사지다당0.5μtg/kg가성공유도대서출현자간전기표형.
Objective To establish an animal model of preeclampsia by injecting ultra-low-dose lipopolysaccharide (LPS) to rats in early pregnancy,and to lay the foundation for further study on mechanisms of preeclampsia.Methods Twenty-four pregnant rats were divided into six groups according to the random number table and were injected with LPS 0.3,0.5,0.7,1.0,2.0 μg/kg or saline 2 ml respectively through tail veins on day 5 of pregnancy.The differences in blood pressure,urinary protein and pathological changes in placenta among groups were compared to confirm the suitable dose of LPS for establishing preeclamptic model.Then another 19 pregnant rats were injected with the chosen dose of LPS slowly through tail veins on day 5 of pregnancy; 15 of which were chosen as model group; the other four were chosen as postpartum group.Three non-pregnant rats were as non-pregnant group.Besides,another 15 pregnant rats were injected with saline as pregnant control group.Systolic blood pressure,urinary protein excretion,placental weight,fetal weight,serum white blood cell counts,blood platelet counts,plasma anti-thrombin-Ⅲ content,D-dimer content were examined and compared among groups with one way analysis of variance; histopathologic studies were also done on the placentas,kidneys and aortas of the rats.Results (1) Placental weight of LPS 0.3 μg/kg group increased compared with control group.One pregnant rats(1/4) in LPS 1.0 μg/kg group and LPS 2.0 μg/kg group died on day 16 of pregnancy as a result of vaginal bleeding.Systolic blood pressure of LPS 0.5 μg/kg group rose steadily,while no significant changes were found in other groups.Urinary protein increased in all LPS groups,while urinary protein of LPS 0.7 μg/kg group and LPS 1.0 μg/kg group peaked on day 12 of pregnancy and then decreased; urinary protein of LPS 0.5 μg/kg group increased most significantly,and fetus in LPS 0.5,0.7 and 2.0 μg/kg groups had lighter body weight.So LPS 0.5 μg/kg was chosen as the suitable dose to establish preeclamptic model.(2)Compared with pregnant control group,model group had higher systolic blood pressure [(124.89±1.79) mm Hg vs (119.02±1.80) mm Hg,LSD test,P=0.03] from day 6 of pregnancy,more urinary protein [(2.02±0.29) mg vs (1.11±0.18) mg,LSD test,P=0.00] from day 9 of pregnancy,more absorbed embryos [3.6％ (7/194) vs 0.0％ (0/200),Fisher exact test,P=0.01] at day 20 of pregnancy,higher incidence of placenta bleeding [4.1％ (8/194) vs 0.0％ (0/200),Fisher exact test,P=0.00] and fetal growth restriction [13.9％ (27/194) vs 6.0％ (12/200),X2=6.92,Fisher exacttest,P=0.01].Model group showed more inflammatory cells infiltration in the placenta,more glomerular mesangial cells,swelling and desquamated of renal tubular epithelial cells compared to control group.Blood pressure and urinary protein of the model group recovered to the baseline at the sixth day of postpartum,and no changes in blood pressure and urinary protein were found in non-pregnant rats.Conclusions Injection of LPS 0.5 μg/kg on day 5 of pregnancy through tail veins could induce the clinical symptoms of preeclampsia in rats,which might be an ideal model for further preeclampsia research.
