CAJ | 학술논문

目的：评价蛋白激酶 Cα（PKCα）?核因子 E2相关因子2（Nrf2）?血红素氧合酶1（ HO?1）信号通路在内毒素休克诱发兔急性肺损伤中的作用。方法健康清洁级雄性新西兰大白兔30只，2月龄，体重2．0～2．5 kg，采用随机数字表法分为3组（ n＝10）：对照组（ C组）、急性肺损伤组（ ALI组）和PKC抑制剂白屈菜赤碱组（ CHE组）。 CHE组腹腔注射白屈菜赤碱8 mg∕kg（溶于0．5 ml二甲基亚砜），30 min后，ALI组和CHE组耳缘静脉注射LPS 5 mg∕kg（溶于2 ml生理盐水）制备内毒素休克诱发急性肺损伤模型。静脉注射LPS或生理盐水6 h时，处死大鼠，取肺组织，光镜下观察病理学结果，并行肺损伤评分，测定肺组织湿重∕干重（ W∕D）比值，采用荧光定量 PCR 法测定 Nrf2 mRNA和HO?1 mRNA的表达水平，采用Western blot方法测定Nrf2和HO?1的表达水平。结果与C组比较，ALI组和CHE组肺损伤评分和W∕D比值升高，肺组织Nrf2、HO?1及其mRNA的表达上调（ P＜0．05）；与ALI组比较，CHE组肺损伤评分和W∕D比值升高，肺组织Nrf2、HO?1及其mRNA的表达下调（ P＜0．05）。结论 PKCα?Nrf2?HO?1信号通路是内毒素休克诱发兔急性肺损伤时机体的内源性保护机制之一。
목적：평개단백격매 Cα（PKCα）?핵인자 E2상관인자2（Nrf2）?혈홍소양합매1（ HO?1）신호통로재내독소휴극유발토급성폐손상중적작용。방법건강청길급웅성신서란대백토30지，2월령，체중2．0～2．5 kg，채용수궤수자표법분위3조（ n＝10）：대조조（ C조）、급성폐손상조（ ALI조）화PKC억제제백굴채적감조（ CHE조）。 CHE조복강주사백굴채적감8 mg∕kg（용우0．5 ml이갑기아풍），30 min후，ALI조화CHE조이연정맥주사LPS 5 mg∕kg（용우2 ml생리염수）제비내독소휴극유발급성폐손상모형。정맥주사LPS혹생리염수6 h시，처사대서，취폐조직，광경하관찰병이학결과，병행폐손상평분，측정폐조직습중∕간중（ W∕D）비치，채용형광정량 PCR 법측정 Nrf2 mRNA화HO?1 mRNA적표체수평，채용Western blot방법측정Nrf2화HO?1적표체수평。결과여C조비교，ALI조화CHE조폐손상평분화W∕D비치승고，폐조직Nrf2、HO?1급기mRNA적표체상조（ P＜0．05）；여ALI조비교，CHE조폐손상평분화W∕D비치승고，폐조직Nrf2、HO?1급기mRNA적표체하조（ P＜0．05）。결론 PKCα?Nrf2?HO?1신호통로시내독소휴극유발토급성폐손상시궤체적내원성보호궤제지일。
Objective To evaluate the role of protein kinase Cα( PKCα)?nuclear factor E2?related factor 2 ( Nrf2)?heme oxygenase?1 ( HO?1) signaling pathway on endotoxic shock?induced acute lung injury ( ALI) in rabbits. Methods Thirty healthy male New Zealand white rabbits, aged 2 months, weighing 2?0-2?5 kg, were randomly divided into 3 groups ( n=10 each) using a random number table: normal control group ( group C);ALI group ( group ALI);PKCα inhibitor chelerythrine group ( group CHE) . In group CHE, chelerythrine 8 mg∕kg ( in 0?5 ml of DMSO) was injected intraperitoneally, and 30 min later, LPS 5 mg∕kg ( in 2 ml of normal saline) was injected via the auricular vein to induce ALI in ALI and CHE groups. The rabbits were then sacrificed at 6 h after injection of LPS or normal saline, and the lungs were removed for examination of the pathological changes which were scored and for determination of wet∕dry lung weight ratio ( W∕D ratio) , and the expression of Nrf2 and HO?1 protein and mRNA. Results Compared with group C, the pathological score and W∕D ratio were significantly increased, and the expression of Nrf2 and HO?1 protein and mRNA was up?regulated in ALI and CHE groups. The pathological score and W∕D ratio were significantly higher, and the expression of Nrf2 and HO?1 protein and mRNA was lower in group CHE than in group ALI. Conclusion The PKCα?Nrf2?HO?1 signaling pathway is one of the endogenous protective mechanisms underlying endotoxic shock?induced ALI in rabbits.