目的 探讨乌司他丁预先给药对双下肢缺血再灌注损伤后血浆细胞因子的影响。方法 30例择期双下肢需上止血带(>150 min)手术的患者,随机分为:对照组(NC组,n=10)、乌司他丁预先给药组(UP1组,n=10)和乌司他丁治疗组(UP2组,n=10)。UP1组于首次上止血带前15 min静脉滴注乌司他丁按6000 U/kg,末次松止血带前15 min再次静脉滴注6000 U/kg;UP2组末次松止血带前15 min给予乌司他丁静脉滴注12 000 U/kg;NC组:末次开放止血带前15 min静脉滴注等容积生理盐水(均10 min内滴完)。3组患者首次上止血带前20 min(缺血前)、末次松止血带后30 min(再灌注后30 min)及术后(再灌注后)1 d、3 d和7 d ,取外周血检测血浆C反应蛋白(CRP)、白介素-6(IL-6)、和肿瘤坏死因子(TNF-α)水平。结果 与缺血前比较,再灌注后30 min、1 d及3 d,3组患者血浆CRP、IL-6、TNF-α水平均显著升高(P<0.05),但UP1组、UP2组与NC组相比明显低于后者[CRP:1 d(11.15±2.32)、(10.48±2.08) mg/l比NC(15.83±4.56)mg/l,3 d (4.29±1.89)、(3.89±1.34) mg/l比NC(6.78±2.95)mg/l;TNF-α:1 d(31.24±8.66)、(29.72 ±8.77) ng/l比NC(44.802 ±11.70)ng/l,3 d (13.75±5.11)、(15.73±4.16)ng/l比NC(20.787±8.05)ng/l;IL-6:1 d(160.80±46.95)、(179.72±35.77)ng/l比NC(329.50±95.34)ng/l,3 d (45.32 ±16.53)、(53.35±17.62)ng/l比NC(79.33±24.93)ng/l,P<0.05],UP2组与UP1组间比较差异均无统计学意义;再灌注后7 d 3组患者血浆细胞因子均恢复正常。结论 乌司他丁预先给药可有效地减轻双下肢缺血再灌注所引起的全身炎性反应,使血浆CRP、IL-6、TNF-α上升幅度明显受抑,从而可有效地阻抑炎性因子介导的组织器官损伤。

Objective To investigate the effects of ulinastatin (UTI) on plasma cytokines following intermittent continuous ischemic reperfusion(IR, cumulative time >150min ) of both lower extremities.Methods Thirty patients, both low extremities bound with tourniquets during operation, were randomly divided into three groups: normal control group(Group NC), UTI pretreatment group 1(Group UP1) and group 2(Group UP2). The patients in Group UP1 were intravenously infused with UTI 6000 U/kg 15 min before the tourniquet application and the last tourniquet loosening, respectively. The patients in Group UP2 were intravenously infused with UTI 12 000 U/kg 15 min only before the last tourniquet loosening, UTI was diluted with 100 ml sodium chloride and infused intravenously within 10 minutes. The patients in Group NC were administered with the same volume sodium chloride. At the time, 20 min before tourniquet apptionhor(before IR); 30 min after last tourniquet lossening(30 min after IR); and 1 d, 3 d, 7 d after IR, the peripheral blood was sampled to measure plasma levels of C reactive protein(CRP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α).Results The levels of CRP, IL-6 and TNF-α in the three groups all rose significantly 30 min, 1 d and 3 d after IR compared with those before IR respectively(P<0.05). But the levels of the cytokines in Group UP1 and UP2 were significant lower than those in Group NC[CRP:1 d(11.15±2.32)、(10.48±2.08)mg/l vs NC(15.83±4.56)mg/l,3 d (4.29±1.89)、(3.89±1.34)mg/l vs NC(6.78±2.95)mg/l;TNF-α:1d(31.24±8.66)、(29.72 ±8.77)ng/l vs NC(44.802 ±11.70)ng/l,3 d (13.75±5.11)、(15.73±4.16)ng/l vs NC(20.787±8.05)ng/l;IL-6:1 d(160.80±46.95)、(179.72±35.77)ng/l vs NC(329.50±95.34)ng/l,3 d (45.32 ±16.53)、(53.35±17.62)ng/l vs NC(79.33±24.93)ng/l,P<0.05]. There were no significant differences between Group UP1 and Group NC in each time in terms of the cytokines(P>0.05). The inflammatory cytokines recovered to the same level 7 d after IR.Conclusions UTI pretreatement may relieve the system inflammatory reaction following both low extremities, prevent the increases of plasma cytokines after IR, thus may attenuate organ damage mediated by cytokines.