Gao Yanguo, Du Guibin, Wu Ying, Wang Qiuyan, Li Rui
Intensive Care Unit, First Affiliated Hospital, Dalian Medical University, Dalian 116021, China. Email:
Zhonghua Yi Xue Za Zhi. 2014 Jan 28;94(4):306-9.
To explore the protective effect of pituitrin on the development of paraquat-induced lung injury in rats.
Sixty healthy Sprague Dawley female rats were randomized into 3 groups of control, paraquat and treatment (80 mg/kg, intragastric) groups (n = 20 each) Each group was divided into 4, 6, 12 and 24 h subgroups (n = 5 each). The treatment group received pituitrin, injection via internal jugular vein 30 minutes after paraquat dosing. As controls, control and paraquat groups were injected with an equal volume of saline. The paraquat content in serum and lung tissue was measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS). And the levels of tumor necrosis factor-alpha (TNF-α) in sera and nuclear factor-kappa B (NF-κB) in lung tissue and the content of protein in bronchoalveolar lavage (BAL) fluid were detected at various timepoints. Lung wet-to-dry weight ratio (W/D) was recorded after pituitrin dosing. In addition, pathological changes were also observed.
The highest drug concentration of paraquat in lung tissue was far lower in the treatment group than that in the paraquat group ((7.67 ± 0.91) vs (13.27 ± 0.95) µg/g, P = 0.002). There were the same result in sera ((1 695 ± 274) vs (5 377 ± 576) ng/ml, P = 0.003). The area under the concentration-time curve in the treatment group was significantly lower than that in the paraquat group (10 482 vs 43 441, P = 0.000). The levels of NF-κB in lung tissue and TNF-α in sera in the treatment group were lower than those in the paraquat group (TNF-α: 24 h: (1.85 ± 0.22) vs (2.59 ± 0.13) ng/ml, P = 0.020; NF-κB: 24 h: (88.0 ± 2.7) vs (101.8 ± 2.8) ng/g, P = 0.003). And there was a decrease in the content of protein in BAL fluid in the treatment group versus the paraquat group (BALF protein: 24 h: (125.9 ± 4.2) vs (192.7 ± 6.5)µg/ml, P = 0.003), lung W/D significantly decreased in the treatment group versus the paraquat group (12 h: 3.50 ± 0.14 vs 3.73 ± 0.15, P = 0.043; 24 h: 3.41 ± 0.06 vs 3.61 ± 0.09, P = 0.047). In addition, when compared with the paraquat group, the pituitrin-treated rats showed a mitigation of inflammatory response in lungs and reduced pulmonary edema.
Pituitrin treatment decreases the content of paraquat in sera and lung homogenate in intoxicated rats and alleviates lung injury so that it may become a useful adjuvant in the treatment of acute lung injury.
探讨垂体后叶素对百草枯诱导的大鼠肺损伤发展的保护作用。
将60只健康的雌性Sprague Dawley大鼠随机分为对照组、百草枯组和治疗组（80mg/kg，灌胃），每组20只。每组再分为4、6、12和24小时亚组（每组5只）。治疗组在给予百草枯30分钟后经颈内静脉注射垂体后叶素。作为对照，对照组和百草枯组注射等体积的生理盐水。采用高效液相色谱-质谱联用（HPLC-MS）法测定血清和肺组织中的百草枯含量。并在不同时间点检测血清中肿瘤坏死因子-α（TNF-α）水平、肺组织中核因子-κB（NF-κB）水平以及支气管肺泡灌洗（BAL）液中的蛋白质含量。记录垂体后叶素给药后的肺湿重/干重比（W/D）。此外，还观察了病理变化。
治疗组肺组织中百草枯的最高药物浓度远低于百草枯组（（7.67±0.91）对（13.27±0.95）μg/g，P = 0.002）。血清中也有相同结果（（1695±274）对（5377±576）ng/ml，P = 0.003）。治疗组的浓度-时间曲线下面积显著低于百草枯组（10482对43441，P = 0.000）。治疗组肺组织中NF-κB水平和血清中TNF-α水平低于百草枯组（TNF-α：24小时：（1.85±0.22）对（2.59±0.13）ng/ml，P = 0.020；NF-κB：24小时：（88.0±2.7）对（101.8±2.8）ng/g，P = 0.003）。与百草枯组相比，治疗组BAL液中的蛋白质含量降低（BALF蛋白：24小时：（125.9±4.2）对（192.7±6.5）μg/ml，P = 0.003），治疗组的肺W/D显著低于百草枯组（12小时：3.50±0.14对3.73±0.15，P = 0.043；24小时：3.41±0.06对3.61±0.09，P = 0.047）。此外，与百草枯组相比，垂体后叶素治疗的大鼠肺内炎症反应减轻，肺水肿减轻。
垂体后叶素治疗可降低中毒大鼠血清和肺匀浆中百草枯的含量，减轻肺损伤，有望成为治疗急性肺损伤的有效辅助药物。
