百草枯致大鼠急性肺损伤时肺组织c-Jun氨基末端激酶和c-Jun的变化

Change of JNK and c-Jun in lung injury associated with paraquat poisoning of rats

目的 探讨百草枯（paraquat，PQ）致大鼠急性肺损伤时肺组织中c-Jun氨基末端激酶（JNK）和c-Jun的变化。亢法将46只大鼠随机分为对照组（10只）、PQ组、PQ±锌原卟啉（ZnPP）组和PQ±氯血红素（Hm）组（每组各12只）。PQ组大鼠腹腔注入PQ（25mg／kg）制造PQ中毒模型；对照组大鼠腹腔注入等量生理盐水；PQ±ZnPP组大鼠在注入PQ前10min注入ZnPP（10mg／kg，10mg／m1）；PQ±Hm组大鼠在注入PQ前10min注入Hm（10mg／kg，10mg／m1）。不同处理后3d，取肺组织常规HE染色和取血测定血浆中丙二醛（MDA）含量；检测肺组织中CO含量；反转录-聚合酶链反应（RT-PCR）检测肺组织血红素氧合酶-1（HO-1）mRNA的表达；Western免疫印迹分析肺组织JNK和c-Jun磷酸化的情况。结果PO组、PQ±ZnPP组和PQ±Hm组血浆中MDA含量、肺组织中CO含量均明显高于对照组，差异有统计学意义（P〈0.05或P〈O．01），与PQ±ZnPP组比较，PQ±Hm组MDA含量降低，而肺组织中CO含量明显升高，差异均有统计学意义（P〈0．01）。PQ组、PQ±ZnPP组和PQ±Hm组的肺组织HO-1mRNA表达、JNK（55．24±9．34、38．15±10．71、128．55±19．43）及c-Jun（23．16±4．85、15．49±3．13、44．89±10．37）磷酸化相对水平较对照组均明显升高，差异有统计学意义（P〈0．01），PQ±Hm组肺组织的HO．1mRNA表达明显高于PQ组，PQ±Hm组JNK及c-Jun磷酸化水平高于PQ组和PQ±ZnPP组，而PQ±ZnPP组JNK及c-Jun磷酸化水平与PQ组相比又有所降低，差异均有统计学意义（P〈0．01或P〈0．05）。结论在PQ致大鼠急性肺损伤时，内源性CO产生增加，肺组织中JNK和c-Jun的磷酸化水平明显升高。

Objective To investigate the change of JNK and c-Jun in lung injury associated with paraquat poisoning of rats. Methods 46 Rats were randomly divided into four groups：PQ group （n= 12）, control group （n=10）,PQ＋ZnPP group （n=12） and PQ＋Hm group （n=12）. The rats were injected with 2% PQ （25 mg/kg·ip） in PQ group. ZnPP and Hemin （ 10 mg/kg, 10 mg/ml） were injected through inguinal vein before intraperitoneal administration of 2% paraquat in PQ＋ZnPP group and PQ＋Hm group respectively. The rats were injected NS （1 ml/kg,ip） in control group. HE dyeing of lung tissue and MDA content of plasma were used for estimating the injury of lung tissue. The content of CO in the lung tissue was determined. The expression of HO-1 mRNA of the lung tissue was detected by the reverse transcription-polymerase chain reaction. The phosphorylation of JNK and c-Jun was evaluated by Western blot analysis. Results The degree of lung injury in PQ group and PQ＋ZnPP group was higher than that in control group and PQ＋Hm group. But in PQ＋ Hm group the degree of lung injury was lower. The content of MDA in PQ group and PQ＋ZnPP group was higher than that in control group and PQ＋Hm group （P〈0.01）. The content of MDA in PQ＋Hm group was higher than that in control group （P〈0.05）. The content of CO in lung tissue in PQ group, PQ＋ZnPP group and PQ＋ Hm group was and （1.08±0.15mg/L） respectively,and higher than that in control group（P〈0.01 ）. The content of CO in lung tissue in PQ＋Hm group was significantly higher than that in PQ＋ZnPP group （P〈0.01）. The expression of HO-1 and the phosphorylation of JNK （55.24 ±9.34,38.15 ±10.71,128.55 ±19.43） and c-Jun （23.16±4.85.15.49±3.13.44.89±10.37） were increased remarkably in PQ group,PQ＋ZnPP group and PQ＋ Hm group. Those in PQ＋Hm group were higher significantly than PQ group and PQ＋ZnPP group （P〈0.01）. Those in PQ＋ZnPP group were lower than PQ group（P〈0.05 ）. Conclusion The increase of CO of lung tissue in rats at the lung injury associated with paraquat poisoning reduces the acute lung injury of rats. The level of JNK and c-Jun phosphorylation increases obviously, especially after Hemin is utilized.