Effect of norepinephrine and hemagglutinin combined with proton pump inhibitor on hemorheology and peripheral blood NO and ET in patients with cirrhosis complicated with upper gastrointestinal bleeding
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摘要: 目的 探讨去甲肾上腺素、血凝酶联合质子泵抑制剂(PPI)治疗对肝硬化合并上消化道出血(UGIB)患者血液流变学及外周血NO、内皮素(ET)的影响。方法 选取2018年1月—2019年1月接受治疗的肝硬化合并UGIB的96例患者为研究对象，随机分为对照组和观察组，每组48例。对照组给予去甲肾上腺素和泮托拉唑治疗，观察组在此基础上给予血凝酶治疗。分别于治疗前后测定血液流变学及血清NO、ET、AT-Ⅱ和血红蛋白含量，测定血清氧化应激反应因子(MDA、ox-LDL、AOPP)和抗氧化酶(SOD、GSH-Px、CAT)含量; 记录2组患者的输血量、止血时间、住院时间以及24 h内的止血率和止血后3 d的出血率; 观察2组患者治疗前后的UGIB危急程度与治疗效果，并记录不良反应发生情况。结果 2组患者治疗前血清相关检测指标的含量比较，差异无统计学意义(P>0.05)。治疗3 d后，2组患者AT-Ⅱ、ET、MDA、ox-LDL和AOPP含量均明显降低(P< 0.05)，NO、SOD、GSH-Px和CAT含量明显升高(P< 0.05)，观察组的含量变化比对照组更显著(P< 0.05)，并且观察组的血液流变学显著高于对照组(P< 0.05)。对照组血红蛋白含量较治疗前显著降低(P< 0.05)，而观察组无显著变化(P>0.05)。观察组患者输血量、止血时间、再出血率、住院时间和UGIB危急程度均明显低于对照组(P< 0.05)，且观察组患者有更高的止血率和治疗有效率(P< 0.05)。2组患者不良反应发生率比较，差异无统计学意义(P>0.05)。结论 去甲肾上腺素、血凝酶联合PPI治疗能显著改善肝硬化合并UGIB患者的出血症状和氧化应激反应，提高外周血NO含量、降低ET含量，改善患者血液流变学，缩短住院时间，有较好的治疗效果，安全性可靠，值得临床推广。Abstract: Objective To explore the effect of norepinephrine, hemagglutinin combined with proton pump inhibitor(PPI) on hemorheology and peripheral blood NO and ET in patients with cirrhosis complicated with upper gastrointestinal bleeding(UGIB).Methods A total of 96 patients with cirrhosis complicated with UGIB who received treatment in our hospital from January 2018 to January 2019 were selected as the research objects and randomly divided into control group and observation group, with 48 cases in each group. Patients in the control group were treated with norepinephrine and pantoprazole, and patients in the observation group were treated with hemagglutinin on the basis of the control group. The hemorheology, the contents of NO, ET, AT-Ⅱand hemoglobin in serum, the contents of oxidative stress factors(MDA, ox-LDL, AOPP) and antioxidant enzymes(SOD, GSH-Px, CAT) in serum were measured before and after treatment, respectively. The blood transfusion volume, hemostatic time, hospital stay, hemostatic rate within 24 h and the bleeding rate in 3 days after hemostasis were recorded in 2 groups. The severity of UGIB and treatment effect before and after treatment were observed in 2 groups, and the incidence of adverse events was recorded.Results There was no significant difference in the contents of serum related indicators between 2 groups before treatment(P>0.05). After 3 d treatment, the contents of AT-Ⅱ, ET, MDA, ox-LDL and AOPP in 2 groups were significantly decreased(P< 0.05), while the contents of NO, SOD, GSH-Px and CAT were significantly increased(P< 0.05). The content changes in the observation group were more significant than those in the control group(P< 0.05), and the hemorheology in the observation group was significantly higher than that in the control group(P< 0.05). The hemoglobin content in the control group was significantly decreased compared with that before treatment(P< 0.05), but there was no significant change in the observation group(P>0.05). The amount of blood transfusion, hemostatic time, rebleeding rate, hospital stay and the critical degree of UGIB in the observation group were significantly lower than those in the control group(P< 0.05), and the observation group had higher hemostatic rate and treatment effective rate(P< 0.05). There was no significant difference in the incidence of adverse events between 2 groups(P>0.05).Conclusion Norepinephrine and hemagglutinin combined with PPI can significantly improve the bleeding symptoms and oxidative stress of patients with cirrhosis complicated with UGIB, increase the content of NO in peripheral blood, reduce the content of ET, improve the hemorheology of patients, and shorten the length of hospital stay. It has good therapeutic effect, safety and the reliability, and is worthy of clinical promotion.
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Key words:
- cirrhosis /
- upper gastrointestinal bleeding /
- norepinephrine /
- hemagglutinin /
- proton pump inhibitor
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表 1 2组治疗前后血管活性因子含量比较
X±S 组别 例数 NO/(mol·L-1) AT-Ⅱ/(pg·mL-1) ET/(ng·L-1) 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 对照组 48 52.63±5.54 61.94±7.251) 5.73±0.78 4.09±0.651) 115.75±19.87 103.08±10.491) 观察组 48 53.86±5.41 72.51±7.221)2) 5.69±0.82 3.53±0.491)2) 117.01±21.02 92.65±9.151)2) 与同组治疗前比较，1)P < 0.05;与对照组比较，2)P < 0.05。 
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表 2 2组治疗前后氧化应激反应因子含量比较
X±S 组别 例数 MDA/(μmol·L-1) ox-LDL/(mmol·L-1) AOPP/(μmol·L-1) 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 对照组 48 9.84±0.53 7.28±0.381) 48.93±2.04 39.07±1.331) 223.48±9.78 171.62±27.041) 观察组 48 9.89±0.64 6.31±0.431)2) 49.42±2.11 31.87±1.011)2) 221.90±10.98 147.57±23.061)2) 与同组治疗前比较，1)P < 0.05;与对照组比较，2)P < 0.05。
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表 3 2组治疗前后氧化酶含量比较
U/mL，X±S 组别 例数 SOD GSH-Px CAT 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 对照组 48 48.92±6.98 63.76±7.761) 42.76±5.77 63.08±5.991) 28.91±2.65 39.37±2.261) 观察组 48 49.43±7.02 72.87±9.231)2) 43.19±6.11 77.24±6.871)2) 28.65±2.38 45.53±2.091)2) 与同组治疗前比较，1)P < 0.05;与对照组比较，2)P < 0.05。
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表 4 2组治疗前后血液流变学指标比较
mpa·s，X±S 组别 例数 全血高切黏度 全血低切黏度 血浆黏度 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 对照组 48 4.91±0.68 6.96±0.761) 6.26±0.77 7.18±0.691) 2.07±0.25 2.73±0.261) 观察组 48 4.42±0.72 7.87±0.931)2) 6.19±0.61 8.24±0.871)2) 2.11±0.38 3.35±0.291)2) 与同组治疗前比较，1)P < 0.05;与对照组比较，2)P < 0.05。
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表 5 2组患者治疗后转归情况比较
组别 例数 输血量/mL 止血时间/h 住院时间/d 止血/例(%) 再出血/例(%) 对照组 48 371.98±34.09 36.23±2.89 13.09±2.87 34(70.83) 11(22.92) 观察组 48 257.01±33.881) 27.18±2.111) 8.99±0.881) 41(85.42)1) 6(12.50)1) 与对照组比较，1)P < 0.05。
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表 6 2组患者治疗前后血红蛋白含量比较
X±S 组别 例数 治疗前 治疗后 对照组 48 72.19±8.63 64.21±4.871) 观察组 48 73.01±9.64 71.65±4.192) 与同组治疗前比较，1)P < 0.05;与对照组比较，2)P < 0.05。
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表 7 2组患者治疗效果比较
例(%) 组别 例数 显效 好转 无效 总有效 对照组 48 10(20.83) 25(52.08) 13(27.08) 35(72.92) 观察组 48 14(29.17) 28(58.33) 6(12.50) 42(87.50)1) 与对照组比较，1)P < 0.05。
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表 8 2组患者UGIB危急程度比较
分，X±S 组别 例数 治疗前 治疗后 对照组 48 18.11±2.54 12.14±1.011) 观察组 48 17.99±2.37 10.76±0.781)2) 与同组治疗前比较，1)P < 0.05;与对照组比较，2)P < 0.05。
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表 9 2组患者不良反应发生情况比较
例(%) 组别 例数 恶心呕吐 腹痛 眩晕嗜睡 血压升高 总不良反应 对照组 48 3(6.25) 2(4.17) 1(2.08) 3(6.25) 9(18.75) 观察组 48 2(4.17) 1(2.08) 1(2.08) 4(8.33) 8(16.67)
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