中华急诊医学杂志  2020, Vol. 29 Issue (2): 193-198   DOI: 10.3760/cma.j.issn.1671-0282.2020.02.0013
肝动脉阻力指数联和血清miRNA-122a对脓毒症休克合并肝损伤的诊断及预后价值
桑珍珍 , 高杰 , 贾春梅 , 李勇     
沧州市中心医院急诊科,061001
摘要: 目的 探讨肝动脉阻力指数(Hepatic artery resistance index,HARI)、miRNA-122a对脓毒症休克合并肝损伤的早期诊断及预后评估的临床价值。方法 选择2016年12月至2019年02月沧州市中心医院EICU收治的176例脓毒症休克患者作为研究对象,根据有无肝损伤分为无肝损伤组(90例)、肝损伤组(86例)。肝损伤组患者再按肝损伤程度分为轻度肝损伤组(20例)、中度肝损伤组(25例)、重度肝损伤组(41例)。脓毒症休克合并肝损伤患者根据28 d转归分为存活组(26例)和死亡组(60例)。选择健康体检者40例作为对照组。分析两组患者的临床资料,采用彩色多普勒超声测定肝动脉阻力指数(HARI),采用反转录-聚合酶链反应(RT-PCR)测定血清miRNA-122a表达量。采用受试者工作特征(receiver operating characteristic,ROC)曲线分析HARI、血清miRNA-122a对脓毒症休克合并肝损伤的早期诊断价值。采用二元Logistic回归分析影响脓毒症休克合并肝损伤患者预后的危险因素。结果 ① 与对照组比较,脓毒症休克无肝损伤组、脓毒症休克合并肝损伤组患者的HARI、血清miRNA-122a呈递增趋势,差异有显著统计学意义(P<0.01)。ROC曲线分析显示,HARI、血清miRNA-122a诊断脓毒症休克合并肝损伤的AUC分别为:0.872[95% CI=(0.813, 0.919)]、0.796 [95% CI=(0.728, 0.854)]。当HARI最佳临界值为0.738时,其诊断脓毒症休克合并肝损伤的敏感度为77.65%,特异度为83.53%。当miRNA-122a表达量最佳临界值为2.80时,其诊断脓毒症相关肝损伤的敏感度为71.76%,特异度为75.29%。当HARI联合miRNA-122a诊断脓毒症休克合并肝损伤的AUC为0.927[95% CI=(0.876, 0.961)],最佳临界值为0.276时,其诊断脓毒症休克合并肝损伤的敏感度为91.76%,特异度为85.29%。②脓毒症休克无肝损伤组与轻度肝损伤组比较,HARI差异无统计学意义(P > 0.05),而血清miRNA-122a差异有统计学意义(P<0.01)。随肝损伤严重程度加重,HARI、血清miRNA-122a呈递增趋势,重度肝损伤组显著高于轻度和中度肝损伤组,差异有显著统计学意义(P<0.01)。③与存活组比较,单因素分析显示,脓毒症休克合并肝损伤28 d死亡组患者的肝损伤严重程度、APACHE Ⅱ评分、SOFA评分、PCT、Lac、miRNA-122a、HARI显著升高,差异有统计学意义(P<0.01)。④二元Logistic回归分析发现,肝损伤严重程度、APACHE Ⅱ评分、SOFA评分、HARI、miRNA-122a是影响脓毒症休克合并肝损伤患者预后的独立危险因素。结论 HARI联合血清miRNA-122a检测对评估脓毒症休克合并肝损伤具有较高的敏感度和特异度,且对预后评估有一定的临床价值。
关键词: 肝动脉阻力指数(HARI)    miRNA-122a    脓毒症休克合并肝损伤    诊断    预后    
Clinical value of hepatic arterial resistance index combined with serum miRNA-122a in diagnosis and prognosis of septic shock complicated with liver injury
Sang Zhenzhen , Gao Jie , Jia Chunmei , Li Yong     
Department of Emergency, Cangzhou central hospital, Cangzhou 061001, Hebei China
Abstract: objective To investigate the clinical value of hepatic arterial resistance index (HARI) and miRNA-122a in the early diagnosis and prognosis of patients with septic shock complicated with liver injury. Methods A total of 176 septic shock patients admitted to EICU of Cangzhou Central Hospital from December 2016 to February 2019 were selected as the research subjects. According to the occurrence of acute liver injury, they were divided into the liver injury group (86 cases) and the non-liver injury group (90 cases). Patients in the liver injury group were further divided into the mild liver injury group (20 cases), moderate liver injury group (25 cases), and severe liver injury group (41 cases) according to the degree of liver injury. Patients with septic shock complicated with liver injury were divided into the survival group (26 cases) and non-survival group (60 cases) according to the 28-day mortality. Forty healthy individuals were selected as controls. The clinical data of the subjects were collected. The HARI was determined by bedside color Doppler ultrasonography. The expressions of miRNA-122a in serum were determined by reverse transcriptase polymerase chain reaction (RT-PCR). Receiver operating characteristic (ROC) curves were used to analyze the value of HARI and serum miRNA-122a in the early diagnosis of septic shock combined with liver injury. Binary Logistic regression was used to analyze the prognostic risk factors of septic shock patients with liver injury. Results ① Compared with the control group, there was an increasing trend of HARI and serum miRNA-122a in patients with septic shock without liver injury and patients with septic shock complicated with liver injury, with statistically significant differences (P < 0.01). ROC curve analysis showed that the AUC of HARI and serum miRNA-122a for the diagnosis of septic shock complicated with liver injury were 0.872 (95% CI: 0.813, 0.919), and 0.796 (95% CI: 0.728, 0.854). When the cut-off of HARI was 0.738, its sensitivity to the diagnosis of septic shock complicated with liver injury was 77.65%, and the specificity was 83.53%; and when the cut-off value of miRNA-122a was 2.80, its sensitivity to the diagnosis of septic shock complicated with liver injury was 71.76%, and the specificity was 75.29%. When the AUC of HARI combined with miRNA-122a for the diagnosis of septic shock complicated with liver injury was 0.927 (95% CI: 0.876, 0.961), the optimal cut-off value was 0.276, and its sensitivity to the diagnosis of septic shock complicated with liver injury was 91.76%, with a specificity of 85.29%.② There was no significant difference in HARI between the non-liver injury group and the mild liver injury group (P > 0.05), while the difference of serum miRNA-122a was statistically significant (P < 0.01). As the severity of liver injury increased, HARI and miRNA-122a expression in patients with septic shock complicated with liver injury showed an increasing trend, with statistically significant differences (P < 0.01).③ Compared with patients with septic shock with liver injury in the survival group, the liver injury severity, APACHE Ⅱ score, SOFA score, PCT, HARI and serum miRNA-122a expression levels were significantly increased in the death group, with statistically significant differences (P < 0.01).④ Binary Logistic regression analysis showed that the severity of liver injury, APACHE Ⅱ score, SOFA score, HARI and serum miRNA-122a were independent risk factors affecting the prognosis of patients with septic shock with liver injury. Conclusions HARI combined with serum miRNA-122a test has high sensitivity and specificity in the evaluation of septic shock with liver injury, and have certain clinical value in the evaluation of prognosis of patients with septic shock with liver injury.
Key words: Hepatic arterial resistance index(HARI)    miRNA-122a    Septic shock with liver injury    Diagnosis    Prognosis    

脓毒症是感染引起机体炎症反应失控导致的危及生命的器官功能障碍[1],可发展为脓毒症休克,而脓毒性休克患者并发肝损伤有较高的死亡率。急性肝损伤可发生在脓毒症的任何阶段,是影响脓毒症患者预后的独立危险因素[2]。床旁超声测定肝动脉阻力指数(hepatic artery resistance index,HARI),具有快速、方便、无创等优点,可以早期观察肝脏的血流灌注情况。有研究报道,miRNA-122a在调控炎症及肝功能方面发挥重要作用[3-4],但其对脓毒症相关肝损伤的诊断效能及预后价值尚缺乏相关研究。本研究通过检测脓毒症休克患者HARI、血清miRNA-122a的表达量,分析其对脓毒症休克合并肝损伤的早期诊断及预后评估的临床价值。

1 资料与方法 1.1 一般资料

选择2016年12月至2019年02月沧州市中心医院EICU收治的176例脓毒症休克患者作为研究对象。

1.1.1 入选标准

所有入组患者均符合脓毒症与脓毒症休克国际处理指南(2016版)的诊断标准[1]。病例资料完整。脓毒症休克合并肝损伤组患者同时符合脓毒症相关肝损伤(sepsis related liver injury,SRLI)诊断标准[5]。所有入组患者年龄18~80岁。

脓毒症与脓毒症休克的诊断标准[1]:脓毒症为感染后器官序贯衰竭评分(SOFA)≥2分;脓毒症休克是指脓毒症患者经充分液体复苏仍存在持续性低血压,需要血管活性药物维持平均动脉压(MAP)≥65 mmHg(1 mmHG=0.133 kPa),血乳酸水平>2 mmol/L。

脓毒症相关肝损伤(sepsis related liver injury,SRLI)诊断标准[5]:血清丙氨酸氨基转移酶(ALT)或结合胆红素(DBil)升高至正常值上线(ULN) 2倍以上;或血清天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)和总胆红素(TB)同时升高,且其中至少有1项升高至ULN 2倍以上。ALT升高定义为 > 80 U/L,TB升高定义为 > 34.1 μmol/L。肝损伤分级:轻度组:1<ALT/ALTULN<3或1<TB/TBULN<2;中度组:3<ALT/ALTULN > <5或2<TB/TBULN<3;重度组:ALT/ALTULN > 5或TB/TBULN > 3。

1.1.2 排除标准

既往有肝脏肿瘤、慢性肝脏疾病、梗阻性黄疸、慢性肝功能障碍急性发作入住EICU者;中毒或药物性肝损伤等非脓毒症原因引起的肝损伤者;年龄<18岁或 > 80岁;住院资料完整性不能满足研究要求者。

1.1.3 伦理学

本研究符合伦理学标准,并经沧州市中心医院伦理委员会批准,所有检查和治疗均获得过患者家属的知情同意。

1.1.4

病例分组根据是否发生肝损伤,分为无肝损伤组(90例)和肝损伤组(86例);脓毒症休克合并肝损伤患者再按肝损伤严重程度分为轻度肝损伤组(20例)、中度肝损伤组(25例)、重度肝损伤组(41例);脓毒症休克合并肝损伤组患者根据28d转归分为生存组(26例)和死亡组(60例)。选择健康体检者40例作为对照组。

1.2 方法

1.2.1采用彩色多普勒超声测定肝动脉阻力指数(HARI)采用飞利浦ELETE彩超(飞利浦公司,荷兰)诊断系统,3~5 MHz探头进行检查,受检者禁食8h以上,仰卧位,经剑突下横向扫查下腔静脉,在下腔静脉前方检测门静脉,在该处门静脉腹侧寻找肝动脉并检测,采样容积接近血管内径,声束与血流方向的夹角小于60°,检测肝动脉阻力指数(HARI)。选取统一切面和测量方式,各项参数均取3个以上心动周期的平均值。

1.2.2采用反转录-聚合酶链反应(RT-PCR)测定血清miRNA-122a表达量患者入院当天(治疗前)采集患者肘静脉血5 mL,离心(3 000 r/min)10 min,取血浆于-80℃保存,待测miRNA-122a、相对表达量。在miRBase上查找目的基因序列,由美国Invitrogen公司设计合成引物,提取血清miRNAs,合成cDNA。以U6作为内参,RT-PCR反应在9700型基因扩增仪中进行,扩增miRNA。RT-PCR反应条件为:95℃,10 min;40个PCR循环(95℃,10s;60℃,60s)。采用2-ΔΔCt相对定量法计算miRNA-122a相对表达量。

1.3 观察指标

记录患者入EICU当日的一般资料,包括年龄、性别、感染部位、乳酸(Lac)、氧合指数OI(PaO2/FiO2)、血常规、生化指标、PCT、机械通气、APACHE Ⅱ评分、SOFA评分等,记录28 d预后。记录患者入EICU当时的肝动脉阻力指数(HARI)、血清miRNA-122a表达量。

1.4 统计学方法

使用SPSS 23.0软件处理数据,计量资料先行正态检验,符合正态分布的计量资料采用均数±标准差(Mean±SD)表示,两组间比较采用独立样本t检验;方差齐者多组间比较采用单因素方差分析;不符合正态分布者以中位数(P25P75)表示,两组间比较用Mann-Whitney U检验,多组间比较用Kruskal-Wallis H检验。计数资料采用χ2检验。绘制受试者工作特征曲线(ROC),评估HARI和血清miRNA-122a对脓毒症休克合并肝损伤的诊断价值。采用二元Logistic回归分析影响脓毒症休克合并肝损伤患者预后的危险因素。以P<0.05为差异有统计学意义,P<0.01为差异有计学意义。

2 结果 2.1 患者一般资料比较

脓毒症休克无肝损伤组患者与肝损伤组患者间性别、年龄、感染部位等差异均无统计学意义(均P>0.05),说明基线资料均衡,具有可比性,见(表 1)。但是,肝损伤组患者的APACHE Ⅱ评分、SOFA评分、PCT、Lac、28 d病死率显著高于无肝损伤组,差异有显著统计学意义(均P<0.01),且随肝损伤程度的加重呈递增趋势,各组间比较差异有统计学意义(均P<0.01),见表 1, 2

表 1 入选病例一般情况 Table 1 Patient characteristics
指标 对照组
(n=40)
无肝损伤组
(n=90)
肝损伤组
(n=86)
x2/Z/F/H//t/t' P
年龄(岁) 58.9±7.8 59.8±12.5 64.9±11.3 1.261 0.313
男性(例,%) 20(50) 56(57.77) 48(55.81) 1.475 0.252
HR(次/min) 65.2±7.6 125.5±15.9 126.7±15.6 0.038 0.874
MAP(mmHg) 75.6±10.5 61.54±9.52 61.48±8.53 0.092 0.793
CVP(mmHg)   7.28±4.23 7.36±4.87 0.745 0.638
NE(μg/kg/min)   0.79±0.15 0.81±0.26 1.236 0.351
Lac(mmol/L)   3.92±1.54 3.87±1.85 0.367 0.574
PaO2/FiO2(mmHg)   129.50±25.36 127.64±27.59 1.482 0.245
PCT(ng/mL) 0.15±0.02 9.47(6.84, 13.30) 15.47(9.84, 33.4) 55.637 <0.001
机械通气(例,%)   117(69.64) 61(70.93) 2.679 0.192
感染部位(例,%)       1.264 0.337
肺及胸腔   18(20.00) 18(20.93)    
腹腔   20(22.22) 21(24.41)    
泌尿系   28(31.11) 28(32.55)    
导管   5(5.55) 5(5.81)    
其他部位a   19(21.12) 14(16.3)    
APACHE Ⅱ评分   21.72±3.65 25.62±3.37 42.51 <0.001
SOFA评分   7.0(5.0, 11.0) 14.0(12.0, 17.0) 37.98 <0.001
28 d病死率n (%)   87(51.78) 60(69.76) 32.69 <0.001
注: a指除肺、胸腔、腹腔、肝胆系统、导管、泌尿系以外其他部位感染,或者感染部位不明;HR,心率;MAP,平均动脉压;CVP,中心静脉压;NE,去甲肾上腺素;Lac,乳酸;PCT,降钙素原;PaO2/FiO2,氧合指数;APACHE Ⅱ,急性生理与慢性健康评分;SOFA,序贯器官衰竭评分

表 2 脓毒症休克合并不同程度肝损伤患者的各指标比较 Table 2 Comparison of various indicators of septic shock patients with different degrees of liver injury
指标 轻度肝损伤组
(n=20)
中度肝损伤组
(n=25)
重度肝损伤组
(n=41)
F/H/x2 P
APACHE Ⅱ评分 16.74±3.51 22.65±3.36c 26.72±3.62cd 35.69 <0.001
SOFA评分 5.0(5.0, 11.0) 9.0(5.0, 11.0)c 15.0(12.0, 18.0)cd 42.37 <0.001
28 d病死率n(%) 11(45) 14(56)c 35(85.36)cd 9.446 0.009
PCT(ng/mL) 9.52(6.97, 13.46) 14.39(9.86, 26.57)c 18.45(11.24, 39.43)cd 30.54 <0.001
注:与轻度肝损伤组比较,cP<0.01;与中度肝损伤组比较,dP<0.01
2.2 入EICU时的HARI、血清miRNA-122a用于脓毒症休克合并肝损伤的早期诊断价值

与对照组比较,脓毒症休克无肝损组、脓毒症休克合并肝损伤的HARI、血清miRNA-122a表达量明显升高,差异有显著统计学意义(P<0.01),见表 3。脓毒症休克无肝损伤组与轻度肝损伤组比较,HARI差异无统计学意义(P > 0.05),而血清miRNA-122a差异有统计学意义(P<0.01)。随肝损伤严重程度加重,HARI、血清miRNA-122a呈递增趋势,重度肝损伤组显著高于轻度和中度肝损伤组,差异有显著统计学意义(P<0.01),见表 4。HARI、血清miRNA-122a诊断脓毒症休克合并肝损伤的AUC分别为:0.872[95% CI=(0.813, 0.919)]、0.796 [95% CI=(0.728, 0.854)]。当HARI最佳临界值为0.738时,其诊断脓毒症休克合并肝损伤的敏感度为77.65%,特异度为83.53%;当miRNA-122a表达量最佳临界值为2.80时,其诊断脓毒症相关肝损伤的敏感度为71.76%,特异度为75.29%;当HARI联合miRNA-122a诊断脓毒症休克合并肝损伤的AUC为0.927 [95% CI=(0.876, 0.961)],最佳临界值为0.276时,其诊断脓毒症休克合并肝损伤的敏感度为91.76%,特异度为85.29%。见图 1

表 3 不同组间HARI、血清miRNA-122a的比较 Table 3 Comparison of HARI and serum miRNA-122a between different groups
指标 对照组
(n=40)
脓毒症休克无肝损伤组(n=90) 脓毒症休克合并肝损伤组(n=86) F P
miRNA-122 1.03±0.02 2.51±0.45a 2.83±0.56ab 52.736 <0.001
HARI 0.657±0.042 0.708±0.035a 0.730±0.016ab 10.454 <0.001
注:与对照组比较,aP<0.01;与脓毒症休克无肝损伤组比较,bP<0.01

表 4 不同严重程度各组入院即刻HARI、血清miRNA-122a的比较 Table 4 Comparison of HARI and serum miRNA-122a immediately after admission in groups with different degree of liver injury
指标 对照组
(n=40)
脓毒症休克无肝损伤组(n=90) 轻度肝损伤组
(n=20)
中度肝损伤组
(n=25)
重度肝损伤组
(n=41)
F P
miRNA-122a 1.03±0.02 2.51±0.45a 2.57±0.34ab 2.84±0.56abc 3.54±0.58abcd 18.236 <0.001
HARI 0.657±0.042 0.708±0.035a 0.714±0.037a 0.726±0.024abc 0.754±0.046abcd 25.379 <0.001
注:与健康对照组比较,aP<0.01;与脓毒症休克无肝损伤组比较,bP<0.01;与轻度肝损伤组比较,cP<0.01;与中度肝损伤组比较,dP<0.01

图 1 HARI、血清miRNA-122a诊断脓毒症休克合并肝损伤的ROC曲线 Fig 1 ROC curve of HARI and serum miRNA-122a in diagnosis of septic shock with liver injury
2.3 预后危险因素的单因素分析结果

单因素分析结果显示,存活组和死亡组患者年龄、性别、WBC、住EICU时间、机械通气时间、肝损伤持续时间等比较,差异无统计学意义(均P > 0.05)。与存活组比较,28 d死亡组患者入EICU时的肝损伤严重程度、HARI、APACHE Ⅱ评分、SOFA评分、PCT、Lac、HARI、血清miRNA-122a的表达量显著升高,差异有统计学意义(均P<0.05)。见表 5

表 5 脓毒症休克合并肝损伤患者死亡影响因素分析 Table 5 Analysis of influencing factors of death in septic shock patients with liver injury
变量 存活组(n=26) 死亡组(n=60) x2/Z/t/t' P
年龄(岁) 57.9±9.8 65.7±12.6 1.236 0.352
男性(例,%) 13(50) 30(50) 0.328 0.573
APACHE Ⅱ评分 14.85±6.53 28.45±7.39 52.746 <0.001
SOFA评分 7.0(5.0, 10.0) 15.0(12.0, 18.0) 63.249 <0.001
住EICU时间(d) 5(2, 8) 12(6, 25) 0.002 0.975
机械通气时间(d) 4(3, 9) 7(5, 11) 1.457 0.298
肝损伤持续时间(d) 6(3, 9) 8(5, 14) 2.659 0.175
WBC(×109/L) 20.58±3.66 23.78±5.48 0.376 0.549
Lac(mmol/L) 3.2(2.5, 7.8) 4.7(3.1, 15.4) 37.58 <0.001
PCT(ng/mL) 7.03(5.26, 15.63) 22.37(17.68, 45.92) 48.07 <0.001
肝损伤严重程度
(轻度/中度/重度)
9/11/6 11/14/35 9.76 0.002
HARI 0.717±0.016 0.732±0.023 0.695 0.046
miRNA-122a 2.51±0.52 3.27±0.36 33.29 <0.001
2.4 危险因素的二元Logistic回归分析结果

肝损伤严重程度、APACHE Ⅱ评分、SOFA评分、HARI、miRNA-122a是影响脓毒症休克合并肝损伤患者预后的独立危险因素,见表 6

表 6 影响脓毒症休克合并肝损伤患者预后独立危险因素的二元Logistic回归分析结果 Table 6 Binary Logistic regression analysis of independent risk factors affecting the prognosis of patients with septic shock combined with liver injury
影响因素 B SE Wald P OR 95%CI
肝损伤严重程度 1.713 0.785 1.927 <0.01 5.544 (2.024, 9.631)
APACHE Ⅱ评分 1.509 0.762 3.967 0.016 4.521 (1.965, 7.323)
SOFA评分 1.546 0.381 7.779 0.001 4.692 (2.538, 8.633)
HARI 1.024 0.047 4.376 0.008 2.784 (1.259, 5.704)
miRNA-122a 1.036 0.487 4.525 0.023 2.815 (1.082, 5.926)
3 讨论

脓毒症休克为脓毒症的一个亚组,具有较高的死亡率,是ICU患者主要死亡原因之一[6],急性肝损伤可发生在脓毒症休克的任何阶段,是预测死亡的一项重要的预警指标。因此,早期诊断脓毒症休克合并肝损伤,及时给予有效的预防及治疗措施对脓毒症休克患者尤为要要。脓毒症相关肝损伤的机制众多[7-9],目前研究认为有以下几项:①肝脏微循环功能障碍,肝脏虽有门静脉和肝动脉双重血液供应,但脓毒症时肝动脉、门静脉血流量均减少。同时脓毒症时,内毒素导致缩血管和扩血管比例失衡、肝窦内皮细胞损伤、白细胞聚集黏附于窦后静脉壁等,导致肝窦内血管阻力的增加,均导致肝脏微循环功能障碍[10]。②肝脏能量代谢障碍,脓毒症时肝细胞线粒体膜上的主要ATP离子通道活性均降低,导致膜的流动性及通透性改变,同时线粒体结构和功能受损,引起肝细胞能量代谢障碍[11]。③炎性因子、介质过度释放入血,形成瀑布式反应,机体免疫抑制,感染失控,导致肝脏甚至全身多器官功能损害。同时炎性介质促进氧自由基释放,引发脂质过氧化,导致肝损伤[12]。④血小板活化因子(platelet activating factor,PAF)的作用,脓毒症时PAF释放增多,促进血小板聚集、活化,在肝脏微血栓形成;同时PAF通过NF-ҡB激活内毒素,加重肝脏[13]。⑤肠道细菌/内毒素移位,随血液循环到达肝脏,导致肝损害[14]

血清丙氨酸氨基转移酶(ALT)、血清天冬氨酸氨基转移酶(AST)和总胆红素(TB)等是目前诊断脓毒症相关肝损伤(sepsis related liver injury,SRLI)最常用的检测指标,但敏感性、特异性欠佳,且受诸多因素影响。而床旁超声测定肝动脉阻力指数(HARI),具有快速、方便、无创等优点,可以早期观察肝脏的血流灌注情况。国内外很多专家及学者对急性病毒性肝炎或急性酒精性肝炎患者的肝动脉阻力指数进行了研究,然而关于脓毒症休克相关的肝动脉阻力指数方面的信息却很少。因此,本研究探讨脓毒症休克合并肝损伤患者肝动脉阻力指数与肝损伤严重程度及临床预后的关系。

正常人肝脏的血供75 %来自门静脉, 25 %来自肝动脉。门静脉与肝动脉间存在着缓冲效应,即当肝动脉血流量减少时,门静脉血流量增加,而门静脉血流量减少时,肝动脉血流量增加。肝动脉阻力指数(hepatic artery resistance index,HARI)是指肝动脉收缩期峰值流速PSV -舒张末期流速(EDV)与PSV之比,反映动脉收缩期与舒张期血流速度的变化梯度, 不受血管形态及取样角度影响。HARI降低提示动脉壁弹性减低, 血流近端存在梗阻或远端血流的阻力下降。HARI增高主要见于胆管内压力增高并扩张时, 由于胆道梗阻, 胆汁淤积而致的毛细胆管周围肝细胞炎性水肿。本研究显示,脓毒症休克患者肝损伤组HARI显著高于无肝损伤组,并随肝损伤程度加重呈递增趋势,对脓毒症休克肝损伤的早期诊断具有较高的临床应用价值。二元Logistic回归分析发现,HARI是影响脓毒症休克合并肝损伤患者预后的独立危险因素。结果表明脓毒症休克合并肝损伤与HARI有密切的关系,其原因为:脓毒症休克时,血压降低,有效循环血容量锐减,脏器灌注不足,肝动脉血流速降低,HARI增加,此时机体为保证重要脏器灌注,胃肠道血管收缩,导致门静脉血流速度降低。另一方面,脓毒症休克患者,通常使用血管活性药,收缩血管,提升血压,从而导致肝脏血管阻力增大,血流量减少。

miRNA-122作为新药肝细胞毒性早期评价标志物具有潜在应用价值,miRNA-122a通过调控靶基因CAT-1、Cycling G1参与蛋白质的合成,进而参与肝细胞的损伤。miRNA-122a能抑制抗凋亡基Bcl-xL、Bcl-2表达,导致大量淋巴细胞凋亡,免疫功能抑制,脓毒症后期感染难以控制。血清miRNA-122a表达量的升高,可以作为脓毒症诊断的特异性标志物, 还能够对脓毒症患者的疾病严重程度及死亡率做出预警[3]。在急性呼吸窘迫损伤综合征患者中,血清miRNA-122a表达量的升高与死亡率和急性肝损伤有相关性。本研究显示,脓毒症休克合并肝损伤组患者血清miRNA-122a表达水平显著高于脓毒症休克无肝损伤组,并随肝损伤程度加重呈递增趋势;脓毒症休克合并肝损伤死亡组患者血清miRNA-122a表达水平显著高于存活组,表明血清miRNA-122a可用于脓毒症休克合并肝损伤的早期诊断、严重程度和预后评估,这与国内外研究报道结果一致。

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