血红素氧合酶-1/一氧化碳系统对老龄脓毒症小鼠蛋白C系统的影响  

The effect of heme oxygenase-1/carbon monoxide on protein C pathway of elderly sepsis rats

作　　者：费东生[1] 刘文[1] 孟祥林[1] 南川川[1] 潘尚哈[1] 赵鸣雁[1] 

机构地区：[1]哈尔滨医科大学附属第一医院重症医学科,黑龙江哈尔滨150001

出　　处：《中国老年学杂志》2013年第1期87-90,共4页Chinese Journal of Gerontology

基　　金：国家自然科学基金(81171785);黑龙江省自然科学基金(ZJY0704-02)

摘　　要：目的探讨血红素氧合酶-1/一氧化碳(HO-1/CO)系统对老龄脓毒症小鼠蛋白C系统的影响。方法采用改良盲肠结扎穿孔术(CLP)制备脓毒症模型。将96只健康C57BL/6雄性小鼠按随机数字表法分为假手术组、CLP组、CLP+HEMIN(HO-1激动剂)组及CLP+ZNPP(HO-1抑制剂)组,各组又按处死时间分为术后6、12、18和24 h亚组,每组6只小鼠。留取血浆检测血浆白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、血栓调节蛋白(TM)、蛋白C(PC)、活化蛋白C(APC)水平;留取肝组织检查各组动物组织血栓形成情况并检测血栓调节蛋白(TM)、蛋白C(PC)表达情况。结果肝脏光镜下可见CLP组及CLP+ZNPP组相对于假手术组血栓形成明显增多,而CLP+HEMIN组较CLP组血栓形成明显减少;CLP组、CLP+HEMIN组及CLP+ZNPP组血浆PC、APC水平均较假手术组明显减少(P<0.05),但CLP+HEMIN组血浆PC、APC水平程度明显高于CLP组及CLP+ZNPP组两组;CLP组、CLP+HEMIN组及CLP+ZNPP组血浆TM水平均较假手术组增加,但CLP+HEMIN组血浆TM水平增加不明显,而CLP组及CLP+ZNPP组血浆TM水平增加显著(P<0.01);肝脏组织免疫荧光及WESTERNBLOT显示CLP+HEMIN组较CLP及CLP+ZNPP组PC及TM表达均有所增加。结论 HO-1/CO系统能够上调脓毒症小鼠的血栓调节蛋白(TM)、蛋白C(PC)表达,促进蛋白C活化,通过促进肝脏PC合成和PC向APC转化、上调TM三个环节减轻脓毒症时蛋白C途径受损,从而通过蛋白C系统途径改善脓毒症小鼠凝血功能障碍。Objective To investigate whether dose heme oxygenase（HO）-1/carbon monoxide impact the anticoagulation by protein C pathway treatment in mouse model of sepsis. Methods Aged septic rats were induced by cecal ligation and puncture （CLP）. 96 C57BL/ 6 rats were randomly assigned into SHAM, CLP, CLP ＋ HEMIN （HO-1 inducer）, and CLP ＋ ZNPP （HO-1 inhibitor） groups. At each of the indicated time points, the plasma levels of tumor necrosis factor alpha （ TNF-α）, protein C （ PC）, thrombin modulation （TM） and activated protein C （APC） were assayed by ELISA. Histopathology examination was performed by Martius-Scarlet-Blue （MSB）staining meth- od. The expressions of TM and PC in liver tissue were tested by Western blot assay. Results Villus of intestinum tenue became hyperemia, hydroncus and with the inflammation , while the expression of TNF-α in plasma was increased highly after CLP（P 〈 0.01 ）. The amount of microthrombus which was detected by microscope in CLP team in liver was exceeded than that of CLP ＋ HEMIN group remarkably. The lev-els of PC and APC in plasma of the other three groups were lower notably than those of CLP group （ P 〈 0. 05 ）, while the level of PC and APC in plasma of CLP ＋ HEMIN team were much higher than those of CLP and CLP ＋ HEMIN groups. But the level of TM in plasma of SHAM group was much lower than that of the other three groups（P 〈 0. 05 ）. While the level of TM in plasma of CLP ＋ HEMIN group was decreased notablely than that of the other two groups （P 〈 0. 05 ）. The levels of PC and TM groups were increased higher in CLP ＋ HEMIN group than those of CLP and CLP ＋ ZNPP groups in liver by immunofluorescence and Western blot. Conclusions HO-1/carbon monoxide could not on-ly up-regulate PC and APC in plasma, but also increase the expressions of TM and PC in liver of sepsis model rats, HO-1/carbon monoxide could decrease the amount of microthrombus to imnrove anticoazulation bv protein C pathway treatment in sepsis model rats

关 键 词：一氧化碳 脓毒症 血栓调节蛋白 蛋白C 

分 类 号：R631[医药卫生—外科学]