不同时段剂量腹腔注射百草枯致小鼠肺损伤及肺纤维化效果评价

目的 观察不同时段、剂量腹腔注射百草枯(PQ)对于小鼠肺损伤及肺纤维化诱导效果的区别,以期建立更为合适、操作简便且结果稳定的肺损伤和/或肺纤维化动物模型.方法 8～10周龄雄性C57BL/6J小鼠,分别采取腹腔注射单次给药(40 mg/kg、50 mg/kg、60 mg/kg),连续给药(10 mg/kg、12.5 mg/kg、15 mg/kg),以及间断给药(20 mg/kg、22.5 mg/kg、25 mg/kg)的方法,同组随机(随机数字法)匹配生理盐水对照组.分别于末次给药后1周、2周处死小鼠.监测小鼠一般情况,体质量状况及病死率.收获日检测肺功能指标;肺泡支气管灌洗液(BALF)细胞计数及分类;羟脯氨酸浓度;以及组织病理学分析.结果 单次或间断腹腔注射不同剂量PQ,均可诱导部分小鼠发生急性肺损伤,早期观察时间点的炎症表现随剂量增高而加重;晚期观察点少量存活小鼠可发生肺间质纤维化.病理切片见损伤部位主要集中在背后段、外周及胸膜下.但以上两组给药方式早期均有较高病死率,故晚期肺纤维化致病率较低.小剂量PQ连续给药法在各时间点诱导C57BL/6J小鼠的肺部病变缺乏显著意义.结论 单次大剂量或间断中等剂量腹腔注射作为PQ全身性给药的方法之一,可以成功诱导出早期小鼠急性肺损伤,但研究终点肺纤维化的致病率较低.PQ小剂量连续给药法致C57BL/6J鼠系肺损伤及肺纤维化的效果不明显.     

Protective effects of chitosan oligosaccharide on paraquat-induced nephrotoxicity in rats

We investigated the apoptotic pathway during paraquat (PQ)-induced nephrotoxicity as well as renoprotective effects of chitosan oligosaccharide (COS) in male Sprague-Dawley rats because increasing evidences suggest that antioxidants may prevent PQ-induced apoptosis. Animals were pretreated with normal saline or COS (500 mg/kg, p.o.) 3 days before PQ (60 mg/kg, i.p.) administration, and were sacrificed at scheduled times after PQ administration. Rats administered PQ showed increased serum PQ concentrations, blood urea nitrogen, and creatinine levels in a time-dependent manner and creatinine clearance was decreased compared with control rats. All of these parameters were reversed significantly by COS pretreatment. After the PQ injection, cell deaths occurred in the proximal renal tubules with increased APE, PUMA, and cleaved caspase-3 expression, while APE and cleaved caspase-3 were immunolocalized mainly in the proximal tubules of control kidneys. COS-pretreated rat kidneys showed increased expression of the above parameters before PQ injection. APE and cleaved caspase-3 were immunolocalized ubiquitously in the renal cortex of COS-pretreated rats until 24 h after the PQ injection. These results showed that PQ-induced nephrotoxicity may be caused by apoptosis in rat kidneys and that COS could protect kidneys from PQ-induced toxicity in association with the basal higher level of APE.     

HPLC法检测人血浆中百草枯的浓度

摘 要 目的:建立检测人血浆百草枯浓度的高效液相色谱方法。方法: 流动相为乙腈-3 mmol·L^-1 SDS-0.2％TFA（35∶28∶37）,流速为1.0 ml·min^-1,检测波长258 nm,柱温35℃,内标为卡马西平。用乙腈沉淀血浆蛋白处理后,进行高效液相色谱分析。结果:血浆百草枯在0.5～100.0 mg·L^-1范围内线性关系良好（r=0.999 8）。高、中、低三个浓度（1.00,10.00,50.00 mg·L^-1 ）的相对回收率分别为（103.06±4.04）％,（100.20±3.00）％和（99.33±2.26）％;日内RSD分别为4.85％,5.97％和4.91％;日间RSD分别为6.60％,5.98％和4.10％。结论:本方法准确可靠,简便快速,适用于百草枯中毒患者的血药浓度检测。     

血液透析加血液灌注救治百草枯中毒79例疗效分析

目的研究血液净化技术对救治百草枯中毒患者的有效方法。方法总结回顾河池市第一人民医院近年来收治的百草枯患者通过血液透析加血液灌注治疗取得的疗效。使用SAS软件统计处理数据,采用χ2检验。结果79例百草枯患者,经血液透析加血液灌注救治,死亡61例(19例死于肺间质纤维化,42例死于多器官功能衰竭),痊愈15例,经救治后病情好转主动要求转院的3例。结论百草枯中毒以高病死率应引起广泛关注。临床上没有特别有效的针对药,要采用药物治疗和血液净化技术联合对百草枯患者进行及早的救治。     

急性百草枯中毒患者肝功能变化及意义

目的：探讨急性百草枯中毒（APP）患者肝功能变化与预后的关系。方法：APP患者46例,以住院期间临床死亡作为观察终点,分为存活组24例、死亡组22例。分别采集患者入院第1、3、7天空腹静脉血进行谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TBIL）、直接胆红素（DBIL）和白蛋白（ALB）检测,两组比较并进行统计学分析。结果：存活组入院第1天ALT、AST、DBIL、ALB,第3、7天ALT、AST、TBIL、DBIL明显低于死亡组（P〈0．05）;存活组入院第1、3、7天ALT逐渐升高（P〈0．05）,ALB逐渐降低（P〈0．05）,而AsT未见明显变化（P〉0．05）;死亡组入院第3天A1月、AST、TBIL、DBIL较入院第1天显著升高（P〈0．01）,入院第3天ALB较第1天显著降低（P〈0．01）。结论：APP患者的肝功能指标变化与中毒程度有关,是判断APP病情严重程度,肝脏损伤情况及预后的可靠指标。     

Occupational paraquat exposure of agricultural workers in large Costa Rican farms

Objective  Paraquat is an herbicide widely used worldwide. This study determined the extent of occupational exposure to paraquat among farm workers in Costa Rica and identified determinants of occupational exposure. Methods  Twenty-four hour urine samples were collected from 119 paraquat handlers and 54 non-handlers from banana, coffee and palm oil farms. Information about herbicide handling operations was also collected. The urinary paraquat levels were determined by an enzyme-linked immunosorbent assay (ELISA) with a limit of quantification (LOQ) of 2 ng/mL. Inhalable dust and airborne paraquat levels were simultaneously measured for a subset of the participants. Results  Urinary paraquat measurements were non-detectable or very low when workers did not handle paraquat. For handlers, 83.3, 47.1 and 63.9% of the samples were below the LOQ on before-, during- and after-paraquat spray days, respectively. The arithmetic mean (±SD) of urinary paraquat level on days when workers handled paraquat was 6.3 (±10.45) μg/24 h. Paraquat exposures among handlers on spray day were significantly associated with the type of crop. Conclusion  Non-handlers had negligible urinary paraquat, while detectable paraquat exposures were observed among handlers on spray day. Urinary paraquat levels were different by crop.     

百草枯致小鼠肺纤维化作用的实验研究

目的探讨百草枯(PQ)对小鼠肺纤维化的作用机制。方法将8周龄健康清洁级雄性C57BL小鼠48只分为百草枯组和对照组(生理盐水),每组24只。百草枯组腹腔注射5mg/ml的百草枯(20mg/kg)连续3d。每天观察并记录各组小鼠的行为学改变。分别于染毒后第1、3、7天处死动物,取肺组织进行普通病理和免疫组化染色,统计肺组织基质金属蛋白酶(MMP-2、MMP-9)阳性细胞数。结果染毒后3d,百草枯组小鼠均出现不同程度的运动障碍、动作迟缓、震颤、竖毛和活动减少。光镜下观察,静脉瘀血、局部出血,中性粒细胞轻度增多,纤维母细胞增多,肺局部纤维组织增生;染毒后7d,出现慢性炎症、出血,局部区域可明显见纤维组织增生,间质增厚。百草枯组小鼠肺组织中MMP-2、MMP-9的表达均强于对照组,差异有统计学意义(P<0.05或P<0.01);且MMP-2、MMP-9的表达随着时间的延长而增强。结论百草枯可引起小鼠肺组织纤维化,MMP-2、MMP-9可能参与了百草枯致肺纤维化的过程。     

An antisense oligonucleotide to HSP47 inhibits paraquat-induced pulmonary fibrosis in rats

The most common cause of death from poisoning by the widely used, but highly toxic herbicide paraquat is respiratory failure from pulmonary fibrosis, which develops through pathological overproduction of extracellular matrix proteins such as the collagens. Heat shock protein (HSP47) is a collagen-specific molecular chaperone that assists in the posttranslational modifications of procollagens during collagen biosynthesis. We investigated whether treatment with an HSP47-antisense oligonucleotide would inhibit paraquat-induced pulmonary fibrosis in Wistar rats. Rats randomized into three groups (control, paraquat, and paraquat+antisense). Paraquat (20 mg/kg/day) (n=16) or a saline control (n=10) was administered to groups of Wistar rats. Intratracheal administration of the antisense oligonucleotide (100 nmol/kg in saline) was performed after the initial paraquat treatment (n=16). Treatment with paraquat alone induced pulmonary fibrosis in the entire group, while treatment with the antisense oligonucleotide alone did not produce any substantial change in lung histology. Administration of antisense oligonucleotides produced a substantial reduction in paraquat-induced pulmonary fibrosis. An immunoblot analysis confirmed that the HSP47-antisense oligonucleotide inhibited HSP47 production. These findings indicate that the HSP47-antisense oligonucleotide inhibited paraquat-induced pulmonary fibrosis and pneumopathy in rats.     

百草枯中毒的急救与护理

百草枯（ PQ）,又名克芜踪,化学名称为1,1＇- 二甲基-4,4＇-联吡啶二氯化物,属接触灭生类除草剂.对人体有较强的毒性,迄今为止仍无特效的解毒剂,临床死亡率极高.我院于2003年5月至2010年2月共收治百草枯中毒患者10例,现将护理体会报道如下.     

序贯性血液净化救治急性百草枯中毒临床研究

目的观察序贯性血液净化救治急性百草枯(paraquat,PQ)中毒的临床疗效。方法选择73例急性PQ中毒患者随机分为对照组和治疗组,对照组给予常规方法治疗,治疗组在对照组基础上给予序贯性血液净化治疗。结果两组治疗7、14 d后除WBC外其他实验室指标比较差异均有统计学意义(均P<0.05),两组治疗后肺部CT表现比较差异均有统计学意义(均P<0.05)。对照组治疗后发生多器官功能衰竭、死亡、存活患者住院时间分别为63.6%、66.7%、(41.5±5.5)d,治疗组分别为27.5%、27.5%、(25.9±4.8)d,两组比较差异均有统计学意义(均P<0.05)。对照组无并发症发生。治疗组在序贯性血液净化过程中出现血压下降4例,经快速补液很快纠正;出现肉眼血尿3例,未行任何特殊处理,序贯性血液净化结束后自然恢复。结论尽早实施序贯性血液净化救治急性PQ中毒能减轻各脏器的损伤,减少肺纤维化的形成,降低死亡率,明显改善患者预后,值得临床推广应用。