急性胰腺炎患者内源性硫化氢水平的变化 及与凝血功能的关系

Change in endogeous hydrogen sulfide in patients with acute pancreatitis and its relationship to coagulation function

目的：探讨急性胰腺炎（AP）患者内源性硫化氢（H2S）水平的变化及与凝血功能的关系。方法采用前瞻性病例对照研究方法。选取2002年12月至2015年3月浙江省义乌市中心医院住院的轻症急性胰腺炎（MAP组）、重症急性胰腺炎（SAP组）患者各40例，以同期40例健康体检者作为对照（健康组）。留取空腹静脉血，测定血浆H2S、凝血因子Ⅷ（FⅧ）、血管性血友病因子（vWF）、纤溶酶原（PLG）、抗凝血酶（AT）、血小板计数（PLT）、组织因子（TF）、肿瘤坏死因子-α（TNF-α）含量及单核细胞蛋白酶激活受体-1（PAR-1）表达水平，并对各指标进行相关性分析。结果3组研究对象性别、年龄、体质量及AP两组间病程比较差异均无统计学意义，具有可比性。与健康组比较，MAP组、SAP组血浆H2S、FⅧ、vWF、TF、TNF-α及单核细胞PAR-1表达均显著升高〔H2S（μmol/L）：67.42±6.34、112.47±12.69比42.57±4.18，FⅧ：（67.5±5.8）%、（82.3±4.7）%比（57.2±6.4）%，vWF：（112.6±9.7）%、（142.5±12.5）%比（76.4±8.2）%，TF（ng/L）：45.27±4.34、64.76±6.25比18.15±1.89，TNF-α（ng/L）：197.67±13.62、324.72±25.54比20.08±2.57， PAR-1（荧光强度）：32.16±4.43、56.12±7.07比12.27±2.12，均P＜0.01〕，血浆PLG、AT活性显著减低〔PLG：（52.4±4.7）%、（36.7±3.2）%比（62.1±5.6）%，AT：（43.2±6.9）%、（35.5±5.4）%比（53.6±6.1）%，均P＜0.01〕，且SAP组各指标升高或降低较MAP组更为显著（均P＜0.01）。SAP组PLT明显低于健康组和MAP组（×109/L：8.5±1.1比15.7±2.8、12.4±1.9，均P＜0.01）。H2S与FⅧ、vWF、TF、TNF-α、PAR-1呈显著正相关（r值分别为0.56、0.61、0.72、0.66、0.64，均P＜0.01），与PLG、AT呈显著负相关（r值分别为-0.64、-0.57，均P＜0.01）。结论 AP患者内源性H2S可上调TF、TNF-α、PAR-1表达水平，从而介导AP患者的凝血功能障碍。

Objective To study the change in endogenous hydrogen sulfide （H2S） in patients with acute pancreatitis and its relationship to coagulation function. Methods A prospective case control study was conducted. Forty patients with mild acute pancreatitis （MAP group） and 40 with severe acute pancreatitis （SAP group） admitted to Yiwu Central Hospital in Zhejiang Province from December 2002 to March 2015 were enrolled. Forty healthy persons served as control （healthy control group）. Blood was collected to determine the levels of H2S, blood coagulation factor Ⅷ （FⅧ）, von Willebrand factor （vWF）, plasminogen （PLG）, antithrombin （AT）, platelet count （PLT）, tissue factor （TF）, tumor necrosis factor-α （TNF-α）, and protease activated receptor-1 （PAR-1）. The correlations among the above parameters were analyzed. Results There was no statistical significance in sex, age, body weight and time of disease among three groups, indicating it was comparable among the groups. Compared with healthy control group, the levels of H2S, FⅧ, vWF, TF, TNF-α, and PAR-1 in MAP and SAP groups were significantly elevated [H2S （μmol/L）： 67.42±6.34, 112.47±12.69 vs. 42.57±4.18, FⅧ： （67.5±5.8）%, （82.3±4.7）% vs. （57.2±6.4）%, vWF： （112.6±9.7）%, （142.5±12.5）% vs. （76.4±8.2）%, TF （ng/L）： 45.27±4.34, 64.76±6.25 vs. 18.15±1.89, TNF-α （ng/L）： 197.67±13.62, 324.72±25.54 vs. 20.08±2.57, PAR-1 （fluorescence intensity）： 32.16±4.43, 56.12±7.07 vs. 12.27±2.12, all P 〈 0.01], and PLG and AT activity were significantly decreased [PLG： （52.4±4.7）%, （36.7±3.2）% vs. （62.1±5.6）%, AT： （43.2±6.9）%, （35.5±5.4）% vs. （53.6±6.1）%, all P 〈 0.01]. The changes in the parameters in SAP group were more remarkable than those in MAP group （all P 〈 0.01）. PLT in SAP group was significantly lower than that in healthy control and MAP groups （×109/L： 8.5±1.1 vs. 15.7±2.8, 12.4±1.9, both P 〈 0.01）. H2S was positively correlated with FⅧ, vWF, TF, TNF-α, and PAR-1 （r value was 0.56, 0.61, 0.72, 0.66, 0.64, respectively, all P 〈 0.01）, and it was negatively correlated with PLG and AT （r value was -0.64, -0.57, both P 〈 0.01）. Conclusion As an inflammatory factor, endogenous H2S deteriorates coagulation function in patients with acute pancreatitis by up-regulating TF, TNF-α, and PAR-1.