郑州大学学报（医学版）
鄭州大學學報（醫學版）
정주대학학보（의학판）
JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES)
2013年
4期
489-492
,共4页
王彦芳%阚全程%余祖江%李朵璐%关克磊
王彥芳%闞全程%餘祖江%李朵璐%關剋磊
왕언방%감전정%여조강%리타로%관극뢰
高血氨%胆红素%氧化应激%血红素加氧酶1%尿苷二磷酸葡萄糖醛酸转移酶1 A1%核因子-κB%大鼠
高血氨%膽紅素%氧化應激%血紅素加氧酶1%尿苷二燐痠葡萄糖醛痠轉移酶1 A1%覈因子-κB%大鼠
고혈안%담홍소%양화응격%혈홍소가양매1%뇨감이린산포도당철산전이매1 A1%핵인자-κB%대서
hyperammonemia%bilirubin%oxidative stress%heme oxygenase-1%UDP-glucuronosyltransferase 1A1%NF-κB%rat
目的：分析高血氨状态下大鼠胆红素水平、胆红素代谢相关的血红素加氧酶1（ HO-1）、尿苷二磷酸葡萄糖醛酸转移酶1A1（ UGT1A1）表达的变化及NF-κB通路的激活情况。方法：25只成年健康雄性Wistar大鼠分为2组：高血氨组15只，每天给予氯化铵灌胃2次；对照组10只，同法灌胃生理盐水。每周心脏采血一次，应用ELISA检测血清总胆红素（ TBIL）与直接胆红素（ DBIL）水平。4周后处死大鼠，心脏灌流后取肝脏，免疫组化SP染色观察HO-1与NF-κB的表达，RT-PCR检测UGT1A1 mRNA的表达水平。结果：高血氨组大鼠血清TBIL、DBIL均较对照组明显升高（TBIL：F组间＝201．524，F时间＝446．552，P 均＜0．001；DBIL：F组间＝131．864，F时间＝455．413，P均＜0．001）。高血氨组HO-1蛋白表达量（2250．31±620．43）较对照组的（156．66±10．28）上调（ t ＝56．829， P＜0．001），高血氨组NF-κB阳性细胞百分比为（0．248±0．052）％，较对照组的（0．072±0．033）％增加（t＝62．347， P＜0．001）。高血氨组UGT1A1 mRNA的表达水平（0．611±0．152）高于对照组的（0．328±0．063）（t＝6．449，P＜0．001）。结论：血氨升高时TBIL和DBIL亦随之升高，HO-1和UGT1A1在组织中的表达增加，提示组织处于氧化应激状态，NF-κB通路被激活。
目的：分析高血氨狀態下大鼠膽紅素水平、膽紅素代謝相關的血紅素加氧酶1（ HO-1）、尿苷二燐痠葡萄糖醛痠轉移酶1A1（ UGT1A1）錶達的變化及NF-κB通路的激活情況。方法：25隻成年健康雄性Wistar大鼠分為2組：高血氨組15隻，每天給予氯化銨灌胃2次；對照組10隻，同法灌胃生理鹽水。每週心髒採血一次，應用ELISA檢測血清總膽紅素（ TBIL）與直接膽紅素（ DBIL）水平。4週後處死大鼠，心髒灌流後取肝髒，免疫組化SP染色觀察HO-1與NF-κB的錶達，RT-PCR檢測UGT1A1 mRNA的錶達水平。結果：高血氨組大鼠血清TBIL、DBIL均較對照組明顯升高（TBIL：F組間＝201．524，F時間＝446．552，P 均＜0．001；DBIL：F組間＝131．864，F時間＝455．413，P均＜0．001）。高血氨組HO-1蛋白錶達量（2250．31±620．43）較對照組的（156．66±10．28）上調（ t ＝56．829， P＜0．001），高血氨組NF-κB暘性細胞百分比為（0．248±0．052）％，較對照組的（0．072±0．033）％增加（t＝62．347， P＜0．001）。高血氨組UGT1A1 mRNA的錶達水平（0．611±0．152）高于對照組的（0．328±0．063）（t＝6．449，P＜0．001）。結論：血氨升高時TBIL和DBIL亦隨之升高，HO-1和UGT1A1在組織中的錶達增加，提示組織處于氧化應激狀態，NF-κB通路被激活。
목적：분석고혈안상태하대서담홍소수평、담홍소대사상관적혈홍소가양매1（ HO-1）、뇨감이린산포도당철산전이매1A1（ UGT1A1）표체적변화급NF-κB통로적격활정황。방법：25지성년건강웅성Wistar대서분위2조：고혈안조15지，매천급여록화안관위2차；대조조10지，동법관위생리염수。매주심장채혈일차，응용ELISA검측혈청총담홍소（ TBIL）여직접담홍소（ DBIL）수평。4주후처사대서，심장관류후취간장，면역조화SP염색관찰HO-1여NF-κB적표체，RT-PCR검측UGT1A1 mRNA적표체수평。결과：고혈안조대서혈청TBIL、DBIL균교대조조명현승고（TBIL：F조간＝201．524，F시간＝446．552，P 균＜0．001；DBIL：F조간＝131．864，F시간＝455．413，P균＜0．001）。고혈안조HO-1단백표체량（2250．31±620．43）교대조조적（156．66±10．28）상조（ t ＝56．829， P＜0．001），고혈안조NF-κB양성세포백분비위（0．248±0．052）％，교대조조적（0．072±0．033）％증가（t＝62．347， P＜0．001）。고혈안조UGT1A1 mRNA적표체수평（0．611±0．152）고우대조조적（0．328±0．063）（t＝6．449，P＜0．001）。결론：혈안승고시TBIL화DBIL역수지승고，HO-1화UGT1A1재조직중적표체증가，제시조직처우양화응격상태，NF-κB통로피격활。
Aim:To explore the influence of hyperammonemia on rat serum bilirubin level , and analyze the changes of bilirubin metabolism related enzyme heme oxygenase-1(HO-1), UDP-glucuronosyltransferase 1 (UGT1A1) and the activa-tion of NF-κB pathway under the state of hyperammonemia .Methods:A total of 25 adult male Wistar rats were allocated into two groups:the 15 rats in high blood ammonia group were given ammonium chloride by gavage twice a day ,and the 10 rats in control group were given normal saline .The blood in heart was drawn out once a week and ELISA was used to deter-mine the levels of serum TBIL and DBIL .The rats were killed after 4 weeks and the liver was removed .Immunohistochem-istry SP staining was used to detect the expressions of HO-1 and NF-κB, and RT-PCR was used to detect the mRNA level of UGT1A1.Results:Serum TBIL and DBIL in high blood ammonia group were significantly higher than those in control group(TBIL:Fgroup =201.524, Ftime =446.522, P<0.001;DBIL: Fgroup =131.864, Ftime =455.143, P<0.001).The expression of HO-1 protein in high blood ammonia group was significantly increased compared with that of control group (2 250.31 ±620.43 vs 156.66 ±10.28, t=56.829, P<0.001).Immunostaining showed deeper nuclear staining of NF-κB in high blood ammonia group [(0.248 ±0.052)% vs (0.072 ±0.033)%, t=62.347, P<0.001].The level of UGT1A1 mRNA in high blood ammonia group(0.611 ±0.152)was higher than that of control group (0.328 ±0.063)(t=6.449, P<0.001).Conclusion: TBIL and DBIL increase with elevating blood ammonia , and the expressions of HO-1 and UGT1A1 in hepatic tissue also increase , suggesting that the organization is in the state of oxidative stress and the NF-κB pathway is activated .
