急性百草枯中毒早期脏器损伤与细胞因子变化规律的研究
摘要
背景百草枯(paraquat,PQ),国内商品名为克无踪。其中毒引起的病死率很高,国外报道病死率为40%～50%,而国内个别报道高达80%以上。百草枯进入人体可使肺、肾、肝和肾上腺出现损伤,而其中毒的特征性改变是肺损伤,表现为早期肺泡上皮细胞受损,肺泡内出血水肿,炎症细胞浸润,晚期则出现肺泡内和肺间质纤维化,这种表现被命名为“百草枯肺”,是急性呼吸窘迫综合征(ARDS)的一种变异形式,也是PQ中毒患者的主要死亡原因。而近年来,肺纤维化机制研究取得了许多非常重要的进展,特别是肺内的多种类型细胞以及细胞因子在这一复杂过程中所起的作用引人注目,从而提出了肺细胞及细胞因子网络的概念。肺泡巨噬细胞及其他肺结构细胞合成的各种细胞因子如转化生长因子-β(TGF-β)、血小板衍生生长因子(PDGF)、胰岛素样生长因子-1(IGF-1)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)白细胞介素-10(IL-10)等在肺纤维化机制研究中取得了非常重要的进展。有资料证明,TGF-β1在肺纤维化的形成与发展中起关键性作用。研究发现,肺泡炎渗出液中有多种细胞生长因子,它们表达的种类、作用浓度和高表达的时间差异以及其相应受体激活程度,对肺泡上皮修复或肺纤维化的发生至关重要,其中TGF-β1是人们关注的热点之一。
目的研究急性百草枯中毒患者脏器损害与血清细胞因子变化规律。
方法38例百草枯中毒患者于服毒后48小时采集静脉血10ml,分离血清,取部分血清立即作肝肾功能及有关生化检查,其余置-70℃冻存,备测细胞因子。采集动脉血2ml行动脉血气检查。所有病人均行高分辨CT检查。对照组为30例健康查体志愿者。肝肾功能和动脉血气分析按照常规方法进行。血清转化生长因子-β(TGF-β)、血小板衍生生长因子(PDGF)、胰岛素样生长因子-1(IGF-1)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)白细胞介素-10(IL-10)采用酶联免疫吸附法(ELISA)。
结果百草枯中毒患者血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、尿素氮(BUN)、肌酐(Cr)、总胆红素(TBIL)较对照组升高明显(P＜0.05或P＜0.01)。患者动脉血氧分压(PO_2)、二氧化碳分压(PCO_2)下降明显,pH、碱剩余(BE)、碳酸氢盐(HCO_3~-)降低明显,与对照组比较差异显著(**P＜0.01),患者血清细胞因子TGF-β、PDGF、IGF-1、TNF-α、IL-10等较对照组明显升高,差异具有显著性(*P＜0.05),而IL-1β、IL-6变化不明显。HRCT主要为肺部渗出性病变,表现为片絮状影、磨玻璃样影、肺叶实变等。
结论;百草枯中毒可造成肺、肝、肾损害,在百草枯中毒发病机制中细胞因子的变化可能起到了重要作用。
Objective To observer the manifestation, liver and renal function, arterial blood gas , lung HRCT of paraquat poisoning patients, and we also determine the serum cytokines PDGF、IGF-1、TNF-α、IL-1β、IL-6、IL-10 of the patients.
Methods 10ml venous blood was drawn from 38 paraquat poisoning patients 48h later after taking poisoning for liver and renal function determination and cytokines detection. Arterial blood gas and lung HRCT were also been done at the same time. 38 volunteers were invited as control. The determination of liver and renal function,arterial blood gas according to routine methods and the detection of cytokines according to the instruction of kits by ELISA.
Results Paraquat could induce respiratory system, digestive system and urinary system manifestation. The serum ALT, AST, TBIL, BUN, Cr were increased by paraquat (P<0.05 or P<0.01, compared with control). PO_2, PCO_2, pH,BE,HCO_3~-were decreased by paraquat (P<0.01, compared with control). Cytokines PDGF、IGF-1、TNF-α、IL-10 were increased by paraquat.
Conclusion Paraquat could induce lung, kidney and liver injury and cytokines may play an important role on the pathogenesis of paraquat poisoning.
目的研究急性百草枯中毒患者脏器损害与血清细胞因子变化规律。
方法38例百草枯中毒患者于服毒后48小时采集静脉血10ml,分离血清,取部分血清立即作肝肾功能及有关生化检查,其余置-70℃冻存,备测细胞因子。采集动脉血2ml行动脉血气检查。所有病人均行高分辨CT检查。对照组为30例健康查体志愿者。肝肾功能和动脉血气分析按照常规方法进行。血清转化生长因子-β(TGF-β)、血小板衍生生长因子(PDGF)、胰岛素样生长因子-1(IGF-1)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)白细胞介素-10(IL-10)采用酶联免疫吸附法(ELISA)。
结果百草枯中毒患者血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、尿素氮(BUN)、肌酐(Cr)、总胆红素(TBIL)较对照组升高明显(P＜0.05或P＜0.01)。患者动脉血氧分压(PO_2)、二氧化碳分压(PCO_2)下降明显,pH、碱剩余(BE)、碳酸氢盐(HCO_3~-)降低明显,与对照组比较差异显著(**P＜0.01),患者血清细胞因子TGF-β、PDGF、IGF-1、TNF-α、IL-10等较对照组明显升高,差异具有显著性(*P＜0.05),而IL-1β、IL-6变化不明显。HRCT主要为肺部渗出性病变,表现为片絮状影、磨玻璃样影、肺叶实变等。
结论;百草枯中毒可造成肺、肝、肾损害,在百草枯中毒发病机制中细胞因子的变化可能起到了重要作用。
Objective To observer the manifestation, liver and renal function, arterial blood gas , lung HRCT of paraquat poisoning patients, and we also determine the serum cytokines PDGF、IGF-1、TNF-α、IL-1β、IL-6、IL-10 of the patients.
Methods 10ml venous blood was drawn from 38 paraquat poisoning patients 48h later after taking poisoning for liver and renal function determination and cytokines detection. Arterial blood gas and lung HRCT were also been done at the same time. 38 volunteers were invited as control. The determination of liver and renal function,arterial blood gas according to routine methods and the detection of cytokines according to the instruction of kits by ELISA.
Results Paraquat could induce respiratory system, digestive system and urinary system manifestation. The serum ALT, AST, TBIL, BUN, Cr were increased by paraquat (P<0.05 or P<0.01, compared with control). PO_2, PCO_2, pH,BE,HCO_3~-were decreased by paraquat (P<0.01, compared with control). Cytokines PDGF、IGF-1、TNF-α、IL-10 were increased by paraquat.
Conclusion Paraquat could induce lung, kidney and liver injury and cytokines may play an important role on the pathogenesis of paraquat poisoning.
引文
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3.Kurniawan AN.Product stewardship of paraquat in Indonesia,Int Arch Occup Environ Health.1996,68;516-518.
4.Hart TB.Paraquat--a review of safety in agricultural and horticultural use,Hum Toxicol.1987,6;13-18.
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6.隋宏,菅向东,楚中华,等..急性百草枯中毒血清细胞因子动态变化的实验研究.毒理学杂志,2007,21;21-23.
7.张政伟,菅向东,阮艳君,等.血必净注射液治疗急性百草枯中毒的实验研究.毒理学杂志,2007,21;23-26.
8.Mohammadi-Karakani A,Ghazi-Khansari M,Sotoudeh M.Lisinopril ameliorates paraquat-induced lung fibrosis,Clin Chim Acta.2006,367;170-174.
9.Bismuth C,Hall AH,Baud FJ,et al.Pulmonary dysfunction in survivors of acute paraquat poisoning.Vet Hum Toxicol,1996,38;220-222.
10.Yamashita M,Yamashita M,Ando Y.A long-term follow-up of lung function in survivors of paraquat poisoning.Hum Exp Toxicol.2000,19;99-103.
11.Gray JP,Heck DE,Mishin V,et al.Paraquat increases cyanide-insensitive respiration in murine lung epithelial cells by activating an NAD(P)H;Paraquat Oxidoreductase;Identification of the enzyme as thioredoxin reductase.J Biol Chem.2007,282;7939-7949.
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2.Bismuth C,Hall AH,Baud FJ et al.Pulmonary dysfunction in survivors of acute paraquat poisoning.Vet Hum Toxicol.1996,38;220-222.
3.Kurniawan AN.Product stewardship of paraquat in Indonesia,Int Arch Occup Environ Health.1996,68;516-518.
4.Hart TB.Paraquat--a review of safety in agricultural and horticultural use,Hum Toxicol.1987,6;13-18.
5.Lin JL,Lin-Tan DT,Chen KH,et al.Repeated pulse of methylprednisolone and cyclophosphamide with continuous dexamethasone therapy for patients with severe paraquat poisoning.Crit Care Med.2007,35;330-331.
6.隋宏,菅向东,楚中华,等..急性百草枯中毒血清细胞因子动态变化的实验研究.毒理学杂志,2007,21;21-23.
7.张政伟,菅向东,阮艳君,等.血必净注射液治疗急性百草枯中毒的实验研究.毒理学杂志,2007,21;23-26.
8.Mohammadi-Karakani A,Ghazi-Khansari M,Sotoudeh M.Lisinopril ameliorates paraquat-induced lung fibrosis,Clin Chim Acta.2006,367;170-174.
9.Bismuth C,Hall AH,Baud FJ,et al.Pulmonary dysfunction in survivors of acute paraquat poisoning.Vet Hum Toxicol,1996,38;220-222.
10.Yamashita M,Yamashita M,Ando Y.A long-term follow-up of lung function in survivors of paraquat poisoning.Hum Exp Toxicol.2000,19;99-103.
11.Gray JP,Heck DE,Mishin V,et al.Paraquat increases cyanide-insensitive respiration in murine lung epithelial cells by activating an NAD(P)H;Paraquat Oxidoreductase;Identification of the enzyme as thioredoxin reductase.J Biol Chem.2007,282;7939-7949.
12.Takizawa M,Komori K,Tampo Y et al.Paraquat-induced oxidative stress and dysfunction of cellular redox systems including antioxidative defense enzymes glutathione peroxidase and thioredoxin reductase.Toxicol In Vitro.2007,21;355-363.
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