乌司他丁对新生大鼠脓毒症肺损伤缓解作用的研究  

Effects of ulinastatin on lung injury in neonatal sepsis rats

作　　者：杨如江 张光成 YANG Ru-jiang;ZHANG Guang-cheng(School of Nursing,Chuzhou City Vocational College,Chuzhou239000,Anhui Province,China;Department 1 of Pediatrics,Children's Hospital,The First People's Hospital of Chuzhou,Chuzhou 239000,Anhui Province,China)

机构地区：[1]滁州城市职业学院护理学院,安徽滁州239000 [2]滁州市第一人民医院儿童医院儿一科,安徽滁州239000

出　　处：《中国临床药理学杂志》2024年第15期2207-2211,共5页The Chinese Journal of Clinical Pharmacology

基　　金：安徽省高等学校自然科学重点研究基金资助项目(2023AH052843);滁州城市职业学院校级自然科学一般研究基金资助项目(2023zkvb01)。

摘　　要：目的探讨乌司他丁减轻新生大鼠脓毒症肺损伤的分子作用机制。方法选取脓毒症诱导肺损伤患儿(脓毒症肺损伤组)及同期出生的健康新生儿(对照组)作为研究对象,采集各组新生儿静脉血备用。将新生SD大鼠随机分为空白对照组(给予等量的0.9%NaCl)、模型组(4 mg·kg^(-1)脂多糖)、乌司他丁组(4 mg·kg^(-1)脂多糖+5×10^(4)U·kg^(-1)乌司他丁),每组12只,在注射24 h内观察大鼠存活情况,24 h后心脏采血后收集肺组织。用实时荧光定量聚合酶链反应法检测血清和肺组织长链非编码RNA(Lnc)CRNDE和miR-29a的表达水平,用酶联免疫吸附试验法检测白细胞介素6(IL-6)水平,用试剂盒法检测活性氧(ROS)水平,用蛋白质印迹法检测血红素氧合酶1(HO-1)的表达水平,用原位荧光杂交实验检测CRNDE和miR-29a的表达水平。结果对照组和脓毒症肺损伤组患儿血清CRNDE相对表达水平分别为1.00±0.16和0.41±0.09,miR-29a相对表达水平分别为1.00±0.14和1.83±0.25,IL-6表达水平分别为(4.13±0.86)和(12.61±2.57)ng·mL^(-1),脓毒症肺损伤组的上述指标与对照组比较,在统计学上差异均有统计学意义(均P<0.05)。空白对照组、模型组和乌司他丁组的肺损伤评分分别为(0.62±0.24)、(4.96±1.28)和(2.13±0.86)分,ROS水平分别为(0.93±0.15)、(2.61±0.35)和(1.58±0.23)U·mg^(-1),HO-1蛋白相对表达水平分别为1.00±0.17、2.19±0.31和1.17±0.16,IL-6水平分别为(46.15±7.62)、(186.77±21.30)和(113.46±14.68)pg·mL^(-1),CRNDE相对表达水平分别为1.00±0.12、0.41±0.06和0.82±0.13,miR-29a相对表达水平分别为1.00±0.14、2.38±0.21和1.62±0.19。空白对照组的上述指标与模型组比较,乌司他丁组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.05)。结论乌司他丁可能通过CRNDE/miR-29a信号通路缓解新生儿脓毒症肺损伤。Objective To investigate the molecular mechanism of ulinastatin in reducing lung injury in neonatal sepsis rats.Methods Sepsis-induced lung injury patients(sepsis lung injury group)and healthy newborns born during the same period(control group)were selected as research subjects,and venous blood from newborns of each group was collected for use.Newborn SD rats were randomly divided into blank control group(given an equal volume of 0.9%NaCl),model group(4 mg·kg^(-1)lipopolysaccharide),and ulinastatin group(4 mg·kg^(-1)lipopolysaccharide+5×10^(4) U·kg^(-1)ulinastatin),with 12 rats in each group.Survival of the rats within 24 hours of injection was observed,and after 24 hours,blood was collected from the heart,and lung tissues were collected.Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression of CRNDE and miR-29a in serum and lung tissue.Enzyme-linked immunosorbent assay was used to detect the expression of inflammatory factors such asinterleukin 6(IL-6).Dual-luciferase reporter gene assay was used to verify the interaction between CRNDE and miR-29a.Kit methods were used to detect reactive oxygen species(ROS)and other oxidative stress indicators.Western blotting was used to detect the expression of heme oxygenase 1(HO-1).In situ fluorescence hybridization was used to detect the expression ofCRNDEandmiR-29a.Results The serum CRNDE expression levels in controlgroup and sepsis lung injury group were 1.00±0.16 and 0.41±0.09,respectively;the expression levels of miR-29a were 1.00±0.14 and 1.83±0.25,respectively;IL-6 levels were(4.13±0.86)and(12.61±2.57)ng·mL^(-1),respectively.Compared with the control group,the above indexes in the sepsis lung injury group were statistically significant(allP<0.05).The lung injury scores of blank control group,model group and ulinastatin group were 0.62±0.24,4.96±1.28,2.13±0.86,respectively;ROS levels were(0.93±0.15),(2.61±0.35),(1.58±0.23)U·mg^(-1),respectively;the protein levels of HO-1 were 1.00±0.17,2.19±0.31,1.17±0.16,res

关 键 词：乌司他丁注射剂 新生儿 脓毒症肺损伤 长链非编码RNA 炎性反应 

分 类 号：R97[医药卫生—药品]