摘要
目的通过观察百草枯染毒大鼠肾组织的变化及中毒后不同时间点血清肌酐水平和肾组织中缺氧诱导因子（HIF）-1α蛋白及转化生长因子（TGF）-β蛋白表达的变化，探讨HIF-1α和百草枯中毒后肾损伤的相关性。方法将48只健康sD雄性大鼠随机分为对照组（6只）和染毒组（42只）：对照组大鼠予生理盐水1ml一次性灌胃；染毒组按照50mg／kg将质量浓度为20％的百草枯原液用生理盐水稀释至1ml后一次性灌胃，按灌胃后2、6、12、24、48、72及120h分为7个亚组，每组6只。分别收集动脉血做血气分析及乳酸和血清肌酐检测；肾组织切片行HE染色；蛋白免疫印迹法（Western blot）法检测肾组织HIF-1α和TGF-β蛋白表达。结果百草枯中毒大鼠在中毒后6h血乳酸和血清肌酐开始升高，与对照组比较，6、12、24、48、72、120h染毒组大鼠乳酸和血清肌酐明显升高，差异有统计学意义（P〈0．05）；72、120h染毒组大鼠出现低氧血症，与对照组的差异有统计学意义（P〈0．05）。6h染毒组大鼠肾组织的HIF-α表达明显升高，72h达高峰，染毒后6、12、24、48、72及120h组HIF-1α蛋白表达与对照组的差异有统计学意义（P〈O．05）。染毒后24hTGF-β蛋白开始升高，72h达高峰，120h呈下降趋势，染毒后24、48、72h组TGF-β蛋白表达与对照组的差异有统计学意义（P〈0．05）。HIF-1α蛋白表达水平与血清肌酐（r=0．9308，P=0．0008）呈正相关；与动脉血氧分压（r=-0．6996，P=0．0534）无相关；与血乳酸（r=0．9483，P=0．0003）呈正相关。肾组织病理学表现主要为肾小管上皮细胞的变性和坏死，并随中毒时间的延长而加重，至120h有好转趋势。结论百草枯中毒后早期肾组织HIF-1α表达明显升高，且和血乳酸、血清肌酐的上升存在相关性，可能同时上调了促肾纤维化因子TGF-β的表达。
Objective To observe the pathological changes of renal tissue in the rats with paraquat （PQ） poisoning as well as the serum crcatinine （SCr） levels and expression levels of hypoxia-inducible factor-1α （HIF-1α ） and transforming growth factor-β（TGF-β） in renal tissue at different time points after PQ poisoning, and to investigate the association of HIF-1α with renal injury after PQ poisoning. Methods Forty-eight healthy male Sprague-Dawley rats were randomly divided into control group （n=6） and PQ group （n=42）. The control group was given a single dose of 1 ml saline by garage; the PQ group was given a single dose of 1 ml PQ （50 mg/ kg）, which was prepared by diluting 20% raw liquid of PQ with saline, by gavage. The PQ group was further divided into 2, 6, 12, 24, 48, 72 and 120h PQ subgroups （n=6 for each subgroup） to be examined at 2, 6, 12, 24, 48, 72, or 120 h after gavage. Their arterial blood was collected for blood gas analysis as well as blood lactic acid （BLA） and SCr measurement; renal sections were subjected to HE staining; the protein expression of HIF- 1α and TGF-β in renal tissue was measured by Western blot. Results The BLA level and SCr level began to rise at 6 h after poisoning. Compared with the control group, the 6, 12, 24, 48, 72 and 120 h PQ subgroups had significantly increased BLA and SCr levels （1）〈0.05）; the 72 and 120 h PQ subgroup showed hypoxemia （P〈 0.05 ）. The protein expression of HIF-1α in PQ group increased significantly at 6 h and reached the peak level at 72 h, with a significant difference from that in the control group at 6, 12, 24, 48, 72, and 120 h （P〈0.05）. The protein expression of TGF-β in PQ group began to rise at 24 h, reached the peak level at 72 h, and declined at 120 h, with a significant difference from that in the control group at 24, 48, and 72 h （P〈0.05）. The protein expression of HIF- 1α was positively correlated with SCr level （r=0.9308, P=0.0008）, uncorrelated with arterialpartial pr
出处
《中华劳动卫生职业病杂志》
CAS
CSCD
北大核心
2013年第1期10-13,共4页
Chinese Journal of Industrial Hygiene and Occupational Diseases
基金
上海市科委课题（10JC1413200）
上海市卫生局课题（20114Y118）
关键词
百草枯
中毒
大鼠
缺氧诱导因子-1Α
转化生长因子-Β
Paraquat
poisoning
Rats
Hypoxia-inducible factor 1 alpha
Transforming growth factor beta
