[1]平 虎,蒲 燕,汤 进,等.乌司他丁对百草枯中毒患者肺纤维化程度及近期生存情况的影响[J].陕西医学杂志,2022,51(8):999-1003.[doi:DOI:10.3969/j.issn.1000-7377.2022.08.022]
　PING Hu,PU Yan,TANG Jin,et al.Effect of ulinastatin on pulmonary fibrosis and short-term survivalin patients with paraquat poisoning[J].,2022,51(8):999-1003.[doi:DOI:10.3969/j.issn.1000-7377.2022.08.022]
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乌司他丁对百草枯中毒患者肺纤维化程度及近期生存情况的影响
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
51
期数:
2022年8期
页码:
999-1003
栏目:
药物与临床
出版日期:
2022-08-05

文章信息/Info

Title:
Effect of ulinastatin on pulmonary fibrosis and short-term survivalin patients with paraquat poisoning
作者:
平 虎; 蒲 燕; 汤 进; 苗云凤; 刘 波
(汉中市中心医院,陕西 汉中 723000)
Author(s):
PING Hu; PU Yan; TANG Jin; MIAO Yunfeng; LIU Bo
(Hanzhong Central Hospital,Hanzhong 723000,China)
关键词:
百草枯中毒;  乌司他丁;  白细胞介素-18;  炎症因子;  氧化应激;  肺纤维化;  生存时间
Keywords:
Paraquat poisoning;  Ulinastatin;  Interleukin-18;  Inflammatory factor;  Oxidative stress;  Pulmonary fibrosis;  Survival time
分类号:
R 595
DOI:
DOI:10.3969/j.issn.1000-7377.2022.08.022
文献标志码:
A
摘要:
目的:探讨乌司他丁对百草枯中毒患者肺纤维化程度及近期生存情况的影响。方法:选择90例百草枯中毒患者,随机分为两组,对照组45例采用常规治疗,干预组45例在常规治疗的基础上给予乌司他丁治疗5 d。治疗后7 d,对两组患者治疗前后促炎细胞因子[白细胞介素-18(IL-18)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、高迁移率族蛋白B1(HMGB1)],促纤维化相关因子[基质金属蛋白酶-9(MMP-9)、转化生长因子-β1(TGF-β1)],氧化应激指标[丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)]以及肝功、肾功、心肌酶指标[谷丙转氨酶(ALT)、谷草转氨酶(AST)、血肌酐(SCr)、肌酸激酶同工酶(CK-MB)等生化指标]进行比较,依据肺CT影像计算并对比两组的肺纤维化程度评分。随后分别对比两组患者7、14、28 d的病死率并采用Kaplan-Meier法对比两组的生存情况。结果:治疗前两组患者的促炎细胞因子、促纤维化相关因子、氧化应激指标以及ALT、AST、SCr、CK-MB等生化指标比较均无统计学差异(均P>0.05)。治疗后7 d,对照组死亡4例(其中1例为第7天死亡)、干预组死亡3例,两组患者的IL-18、TNF-α、IL-6、HMGB1、MMP-9、TGF-β1均较前升高但干预组低于对照组,MDA较前降低且干预组低于对照组,SOD和CAT较前升高且干预组高于对照组,ALT、AST、SCr、CK-MB虽均较前升高但干预组均低于对照组,差异均有统计学意义(均P<0.05); 干预组的肺纤维化程度评分显著低于对照组(P<0.05)。干预组的7 d病死率及生存时间与对照组比较无统计学差异(P>0.05),但14 d病死率显著低于对照组且生存时间显著高于对照组(均P<0.05),然而28 d病死率及生存时间与对照组比较却无统计学差异(均P>0.05)。结论:在常规治疗的基础上联合乌司他丁治疗百草枯中毒,可改善肺纤维化程度及肝、肾、心肌等损伤情况,且可降低14 d病死率并改善生存时间; 其机制为乌司他丁可改善患者的炎性反应及氧化应激失衡、改善肺纤维化,进而降低百草枯所致器官损伤。
Abstract:
Objective:To explore the effect of ulinastatin on the degree of pulmonary fibrosis and short-term survival in patients with paraquat poisoning.Methods:A total of 90 patients with paraquat poisoning were randomly divided into two groups.The control group(45 cases)was treated with routine treatment and the intervention group(45 cases)was treated with ulinastatin on the basis of control group for 5 days.Seven days after treatment,the serum indexes [including pro-inflammatory cytokines(IL-18,TNF-α,IL-6,HMGB1),pro-fibrosis related factors(MMP-9,TGF-β1),oxidative stress indexes(MDA,SOD,CAT),liver function,kidney function and myocardial enzyme indexes(ALT,AST,SCr and CK-MB)]of the two groups before and after treatment were compared.The pulmonary fibrosis degree scores of the two groups were calculated according to lung CT images and then compared.Then,the mortality at 7,14 and 28 days of the two groups were compared,and the survival of the two groups were compared by Kaplan-Meier method.Results:There was no significant difference in pro-inflammatory cytokines,pro-fibrosis related factors,oxidative stress indexes and biochemical indexes such as ALT,AST,SCr and CK-MB before treatment between the two groups(all P>0.05).Seven days after treatment,4 patients died in the control group(1 of them died on the 7th day)and 3 patients died in the intervention group,and IL-18,TNF-α,IL-6,HMGB1,MMP-9 and TGF-β1 in the two groups were higher than those before treatment,but those in the intervention group were lower than those in the control group(all P<0.05); MDA was lower than that before treatment,and that in the intervention group was lower than that in the control group(all P<0.05); SOD and CAT were higher than those before treatment,and those in the intervention group were higher than those in the control group(all P<0.05); ALT,AST,SCr and CK-MB were higher than those before treatment,and those in the intervention group were lower than those in the control group(all P<0.05); the score of pulmonary fibrosis degree in the intervention group was significantly lower than that in the control group(P<0.05).There was no significant difference in 7-day and 28-day mortality and survival time between the two groups(all P>0.05).The 14-day mortality was significantly lower and the survival time was significantly higher in the intervention group than those in the control group(all P<0.05).Conclusion:On the basis of routine treatment,the combined use with ulinastatin in the treatment of paraquat poisoning can improve the degree of pulmonary fibrosis and the injury of liver,kidney and myocardium,reduce the short-term mortality of 14 days and improve the survival time.The mechanism is that ulinastatin can improve patients' inflammatory response and oxidative stress imbalance,improve fibrosis,and then reduce organ damage caused by paraquat.

参考文献/References:

[1] 付国强,王建宇,姚家久,等.急性百草枯中毒患者血清程序性死亡因子1水平变化及与肺纤维化的相关性[J].中国医药,2021,16(3):369-372.
[2] 李辞茹.百草枯中毒致肺纤维化临床治疗及分子机制研究进展[J].医学研究生学报,2020,33(3):322-326.
[3] 黄 坤,杨一红,闫 敏.急性百草枯中毒的预后因素探讨[J].中国急救复苏与灾害医学杂志,2021,16(5):533-535.
[4] 李 军,黄 甫.清胰汤联合乌司他丁治疗重症胰腺炎效果及对患者免疫功能的影响[J].陕西中医,2018,39(10):1393-1395.
[5] 潘龙飞,王立明,牛泽群,等.乌司他丁联合奥曲肽对重症急性胰腺炎患者炎症风暴和肺损伤的作用及机制[J].肝胆胰外科杂志,2021,33(3):147-151.
[6] 中国医师协会急诊医师分会.急性百草枯中毒诊治专家共识(2013)[J].中国急救医学,2013,33(6):484-489.
[7] 宫 平,肖青勉,李百艳,等.百草枯解毒成方辅助治疗对急性百草枯中毒患者血Ⅰ型胶原蛋白和Ⅲ型前胶原肽及转化生长因子β1的影响[J].中国医药,2020,15(3):419-422.
[8] 王瑜贵,张海文,田二云.血液滤过对百草枯中毒患者血清AST、cTnI、AMS及炎症因子水平的影响[J].川北医学院学报,2021,36(5):627-631.
[9] 雷亚莉,张新彧,刘 瑛.急性百草枯中毒肺损伤机制和临床治疗研究进展[J].陕西医学杂志,2018,47(11):1510-1513.
[10] 孙云晖,王一新,马雪梅,等.大鼠肺纤维化模型中NLRP3、IL-18表达及意义的探讨[J].临床肺科杂志,2018,23(5):817-820.
[11] Chen H,Fu X.Dynamics study on the role of curcumin on TGF-β1 expression and pathological changes in acute paraquat poisoned rats[J].Exp Ther Med,2018,16(5):3841-3846.
[12] 高 璠,汪 鑫,杨 冉,等.HMGB1/TLR4介导狼疮性肾炎肾小球细胞增殖和细胞外基质沉积[J].中国药理学通报,2021,37(1):125-131.
[13] Li G,Wu X,Yang L,et al.TLR4-mediated NF-κB signaling pathway mediates HMGB1-induced pancreatic injury in mice with severe acute pancreatitis[J].Int J Mol Med,2016,37(1):99-107.
[14] 刘家燕,王 鑫,李康然,等.乌司他丁治疗百草枯中毒患者的临床疗效及对炎性细胞因子、T淋巴细胞亚群的影响[J].河北医科大学学报,2021,42(10):1149-1154.
[15] Ntshalintshali SD,Manzini TC.Paraquat poisoning:Acute lung injury-a missed diagnosis[J].S Afr Med J,2017,107(5):399-401.
[16] 杨长爽,徐 龙,杨陟华,等.TGF-β3通过调控MMP-9/TIMP-1比例和VEGF表达延缓小鼠放射性肺纤维化[J].军事医学,2017,41(2):81-85.
[17] 王 晔,郝 丽,王 南,等.TGF-1β和MMP-2/MMP-9mRNA在PQ中毒鼠肺中的表达及Ac-SDKP保护作用[J].昆明医科大学学报,2019,40(11):34-38.
[18] 陈 宏,张 伟,郭建波,等.地龙提取物通过抑制TGF-β1信号通路发挥抗肺纤维化作用研究[J].陕西中医,2021,42(4):427-429.
[19] 李荣霞.乌司他丁联合血液灌流对百草枯中毒患者肾功能、纤维化指标及氧化应激指标的影响[J].海南医学院学报,2018,24(12):1155-1158.
[20] 王 鑫,李 兵,孙桂芹,等.乌司他丁对急性百草枯中毒大鼠血浆中炎性细胞因子及MDA、SOD影响的研究[J].现代中西医结合杂志,2015,24(23):2527-2529,2616.
[21] 郝昱芳,安巧和.乌司他丁联合谷氨酰胺治疗急性重症胰腺炎对患者血清淀粉酶、前白蛋白和白蛋白的影响[J].陕西医学杂志,2020,49(10):1325-1328.
[22] Guo H,Jiang C,Sun X.Therapeutical effects and mechanism of salubrinal combined with ulinastatin on treating paraquat poisoning[J].Cell Biochem Biophys,2014,70(3):1559-1563.
[23] Wen C,Lin F,Huang B,et al.Metabolomics analysis in acute paraquat poisoning patients based on UPLC-Q-TOF-MS and machine learning approach[J].Chem Res Toxicol,2019,32(4):629-637.

更新日期/Last Update: 2022-08-04