连续性血液透析滤过对四氯化碳模型大鼠肝肾肠功能的保护作用

Protective effect of continuous blood purification on liver,kidney,and intestinal function in rats with oral carbon tetrachloride poisoning

背景四氯化碳(carbon tetrachloride,CCl_(4))中毒是化工从业人员常见的中毒类型,但目前尚无特效的临床药物能治疗此类中毒导致的肝、肾、肠损伤.目的探索连续性血液透析滤过(continuous blood purification,CBP)对口服CCl4中毒大鼠肝、肾、肠功能的保护作用及其潜在干预机制.方法将斯泼累格·多雷大鼠分为对照组、模型组(CCl4)和CBP治疗组(CCl_(4)+CBP),利用CCl4灌胃建立大鼠模型.收集外周血用于检测白细胞和中性粒细胞数以及血清尿素氮(blood urea nitrogen,BUN)、肌酐(creatinine,Cr)、C反应蛋白(C-reactive protein,CRP)、谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(alanine aminotransferase,AST)、D-乳酸(D-lactic acid,D-LA)、肠性脂肪酸结合蛋白(intestinal fatty acid binding protein,I-FABP)和降钙素(procalcitonin,PCT)的水平.将收集的肝肾肠组织进行相关病理检测,免疫组化法和免疫印迹法检测核转录因子(nuclear transcription factor-κB,NF-κB)通路的相对表达水平.结果CBP处理可显著降低CCl_(4)引起的白细胞和中性粒细胞增多(P<0.05)以及血清BUN、Cr、CRP、ALT、AST、D-LA、I-FABP和PCT的水平的增高(P<0.05),并降低肾脏组织中损伤标记物中性粒细胞明胶酶相关脂质运载蛋白的表达以及肝、肾、肠相关病理形态改变.免疫组化和免疫印迹法检测显示,CBP处理能降低CCl4引起的NF-κB通路激活(P<0.05).结论CBP对CCl4引起的肝、肾、肠损伤具有保护效果,其可能通过降低CCl_(4)引起NF-κB通路激活从而改善肝、肾、肠损伤的症状.

BACKGROUND Carbon tetrachloride(CCl_(4))poisoning is a common type of poisoning in chemical workers,but there is no specific clinical drug available to treat liver,kidney,and intestinal injuries caused by this kind of poisoning.AIM To explore the protective effect of continuous blood purification(CBP)on liver,kidney,and intestinal function in rats with oral CCl_(4) poisoning and the potential mechanism involved.METHODS Sprague-Dawley rats were divided into control group,model group(CCl_(4)),and CBP treatment group(CCl4+CBP).The rat model was established by gavage of CCl_(4).Peripheral blood samples were collected to detect the number of white blood cells and neutrophils,and the levels of blood urea nitrogen(BUN),creatinine(Cr),C-reactive protein(CRP),alanine aminotransferase(ALT),aspartate aminotransferase(AST),D-lactic acid(D-LA),intestinal fatty acid binding protein(I-FABP),and procalcitonin(PCT).Liver,kidney,and intestinal tissues were collected for pathological examination,and the relative protein expression level of nuclear transcription factor-κB(NF-κB)pathway molecules was detected by immunohistochemistry and Western blot.RESULTS CBP treatment significantly reduced the increase of white blood cell and neutrophil counts(P<0.05)and the increase of serum BUN,Cr,CRP,ALT,AST,D-LA,I-FABP and PCT(P<0.05)induced by CCl4.CBP treatment also reduced the expression of neutrophil gelatinase-associated lipocalin in kidney tissue and the pathological changes in the liver,kidney,and intestine.Immunohistochemistry and Western blot showed that CBP treatment could reduce the activation of the NF-κB pathway induced by CCl_(4)(P<0.05).CONCLUSION CBP has a protective effect against liver,kidney,and intestinal injuries induced by CCl4,and it may improve the symptoms of liver,kidney,and intestinal injuries by reducing the activation of the NF-κB pathway induced by CCl_(4).