中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2011年
36期
2573-2577
,共5页
王丽卿%祝胜美%周衡俊%潘彩飞
王麗卿%祝勝美%週衡俊%潘綵飛
왕려경%축성미%주형준%반채비
肝功能衰竭%肝性脑病%硫代乙酰胺%脑水肿
肝功能衰竭%肝性腦病%硫代乙酰胺%腦水腫
간공능쇠갈%간성뇌병%류대을선알%뇌수종
Liver failure%Hepatic encephalopathy%Thioacetamide%Brain edema
目的 探讨水通道蛋白-4(AQP4)在急性肝衰竭肝性脑病与脑水肿的相关性。方法 采用硫代乙酰胺(TAA)腹腔注射制备急性肝衰竭肝性脑病大鼠模型。将健康雄性SD大鼠随机分为对照组8只和模型组24只，其中模型组根据造模后处死大鼠时间不同，分为24、48、60h组。观察大鼠一般情况，评估HE等级，测定血浆丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素和血氨，观察肝组织病理学，检测脑含水量和脑组织AQP4（包括蛋白和mRNA）表达水平。结果 模型组大鼠表现出典型肝性脑病症状，随着造模后观察时间延长，HE等级进行性升高，肝脏生化和血氨水平较对照组显著升高(P＜0.05)，肝组织病理变化与对照组差异有统计学意义。脑含水量和AQP4表达水平（包括蛋白和mRNA）明显高于对照组(P＜0.05)，并且AQP4蛋白和mRNA表达水平分别与脑含水量呈正相关(r =0.536，P＜0.01；r=0.566,P=0.01)。结论 急性肝衰竭肝性脑病大鼠脑水通道蛋白-4(AQP4)表达与脑水肿密切相关，因此AQP4是急性肝衰竭肝性脑病脑水肿发生发展的重要分子机制之一。
目的 探討水通道蛋白-4(AQP4)在急性肝衰竭肝性腦病與腦水腫的相關性。方法 採用硫代乙酰胺(TAA)腹腔註射製備急性肝衰竭肝性腦病大鼠模型。將健康雄性SD大鼠隨機分為對照組8隻和模型組24隻，其中模型組根據造模後處死大鼠時間不同，分為24、48、60h組。觀察大鼠一般情況，評估HE等級，測定血漿丙氨痠轉氨酶、天鼕氨痠轉氨酶、總膽紅素和血氨，觀察肝組織病理學，檢測腦含水量和腦組織AQP4（包括蛋白和mRNA）錶達水平。結果 模型組大鼠錶現齣典型肝性腦病癥狀，隨著造模後觀察時間延長，HE等級進行性升高，肝髒生化和血氨水平較對照組顯著升高(P＜0.05)，肝組織病理變化與對照組差異有統計學意義。腦含水量和AQP4錶達水平（包括蛋白和mRNA）明顯高于對照組(P＜0.05)，併且AQP4蛋白和mRNA錶達水平分彆與腦含水量呈正相關(r =0.536，P＜0.01；r=0.566,P=0.01)。結論 急性肝衰竭肝性腦病大鼠腦水通道蛋白-4(AQP4)錶達與腦水腫密切相關，因此AQP4是急性肝衰竭肝性腦病腦水腫髮生髮展的重要分子機製之一。
목적 탐토수통도단백-4(AQP4)재급성간쇠갈간성뇌병여뇌수종적상관성。방법 채용류대을선알(TAA)복강주사제비급성간쇠갈간성뇌병대서모형。장건강웅성SD대서수궤분위대조조8지화모형조24지，기중모형조근거조모후처사대서시간불동，분위24、48、60h조。관찰대서일반정황，평고HE등급，측정혈장병안산전안매、천동안산전안매、총담홍소화혈안，관찰간조직병이학，검측뇌함수량화뇌조직AQP4（포괄단백화mRNA）표체수평。결과 모형조대서표현출전형간성뇌병증상，수착조모후관찰시간연장，HE등급진행성승고，간장생화화혈안수평교대조조현저승고(P＜0.05)，간조직병리변화여대조조차이유통계학의의。뇌함수량화AQP4표체수평（포괄단백화mRNA）명현고우대조조(P＜0.05)，병차AQP4단백화mRNA표체수평분별여뇌함수량정정상관(r =0.536，P＜0.01；r=0.566,P=0.01)。결론 급성간쇠갈간성뇌병대서뇌수통도단백-4(AQP4)표체여뇌수종밀절상관，인차AQP4시급성간쇠갈간성뇌병뇌수종발생발전적중요분자궤제지일。
ObjectiveTo investigate the expression of aquaporin-4 (AQP4) during brain edema in rats with thioacetamide-induced acute liver failure and encephalopathy. MethodsThe rat model of acute hepatic failure and encephalopathy was induced by intraperitoneal injection of thioacetamide (TAA) at a 24-hour interval for 2 consecutive days. Thirty-two SD rats were randomly divided into the model group ( n =24) and the control group (normal saline, n = 8).And then the model group was further divided into 3 subgroups by the timepoint of decapitation : 24 h ( n = 8 ), 48 h ( n = 8 ) and 60 h ( n = 8 ). Then we observed their clinical symptoms and stages of HE, indices of liver function and ammonia, liver histology and brain water content. The expression of AQP4 protein in brain tissues was measured with Western blot and the expression of AQP4mRNA with RT-PCR(reverse transcription-polymerase chain reaction ).Results Typical clinical manifestations of hepatic encephalopathy occurred in all TAA-administrated rats. The model rats showed the higher indices of ALT (alanine aminotransferase), AST (aspartate aminotransferase), TBIL (total bilirubin) and ammonia than the control rats (P ＜0. 05). The brain water content was significantly elevated in TAA-administrated rats compared with the control (P ＜0. 05 ). The expressions of AQP4 protein and mRNA in brain tissues significantly increased in TAA-administrated rats (P ＜ 0.05 ). In addition, the expressions of AQP4 protein and mRNA were positively correlated with brain water content( r = 0. 536, P ＜0. 01; r =0. 566, P =0. 01 ). ConclusionsThe high expression of AQP4 in rats with TAA-induced acute liver failure and encephalopathy plays a significant role during brain edema. AQP4 is one of the molecular mechanisms for the occurrence of brain edema in hepatic encephalopathy.
