C5a反义肽对脓毒症凝血异常及其急性肺损伤发病的影响

Effects of C5a anti - sense peptide on sepsis - induced abnormal coagulation and acute lung injury

目的观察C5a反义肽对脓毒症凝血异常及ALI发病的影响。方法盲肠结扎穿孔复制小鼠脓毒症ALI模型，随机（随机数字法）分为健康组、假手术组、造模组和C5a反义肽干预组，分别在2，4，8，12h时点观察肺组织损伤的病理改变和凝血指标；并采用ELISA检测血浆TF质量浓度的变化。结果盲肠结扎穿孔后，2h后出现肺组织炎症细胞浸润、蛋白渗出和毛细血管内弥漫血栓形成，并进行性加重；而反义肽干预后的不同时间点上述病理改变均显著改善。造模组和C5a反义肽干预组，PT，TT，APTF进行性延长和DD进行性升高，而Fbg和PLT计数进行性降低，与健康组和假手术组比较P〈0．05；而与造模组比较，反义肽干预后相应时间点的各指标明显改善（P〈0．05）。TF质量浓度在健康组、假手术组分别为（42．75±1．25）pg／mL和（60．73±1．43）pg／mL；造模组2，4，6，12h时点其浓度进行性升高，其中，12h组最高为（139．81±6．17）pg／mL；而与造模组相比，反义肽组各相应时间点明显降低，12h组为（121．41±7．21）pg／mL，各组比较有统计学意义（P〈0．05）。结论C5a反义肽能改善脓毒症的促凝亢进与ALI／ARDS的病理改变。

Objective To investigate the effects of C5a anti - sense peptide on the pathogenesis of sepsis -induced abnormal coagulation and acute lung injury （ALl） in the early stage of sepsis. Methods The method of cecal ligature and puncture （CLP） was used to establish sepsis model. Mice were randomly （random number） divided into control group, sham operation group, model group and C5a anti- sense peptide treatment group. In each group, pathological changes of the lung tissue and coagulation marker of mice were observed at intervals of 2 h, 4 h, 8 h and 12 hours after CLP. Meanwhile, the blood levels of tissue factor （TF） were detected by using ELISA at various intervals. Results The microscopic examination showed that inflammatory cell infiltration, fibrin exudation and DIC occurred in lung tissue of mice in model group 2 hours after CLP, and those changes significantly lessened in mice of the treatment group. The levels of PT, TT, APTT and fragment D - dimer （ DD ） were significantly increased as time consumed, while fibrinogen （Fbg） and platelet （PLT） gradually and significantly decreased in model group and treatment group compared with control group and sham operation group （ P 〈 0.05 ） , and those changes were greatly minimized in the treatment group than those in model group （ P 〈 0. 05 ）. The level of TF was （42. 75 ±1.25） pg/mL in mice of control group and （60. 73 ±1.43 ） pg/mL in mice of sham operation group. The level of TF of mice in model group gradually increased as time consumed to reach the highest level of （ 139. 81 ±6. 71 ） pg/mL in 12 hours. Compared with model group, TF was （ 121.41 ±7.21 ） pg/mL in the intervention group （P 〈 0. 05 ）. Conclusions C5a anti -sense peptide can lessen the coagulation hyperactivity and ALI/ARDS symptoms in the early stage of sepsis.