葛根素对急性胰腺炎患者血栓前状态分子标志物的影响

Changes of molecular markers of prothrombotic c state in plasma and puerarin for treatment of acute pancreatitis

目的研究急性胰腺炎（AP）时血栓前状态分子标志物血小板颗粒膜蛋白-140（GMP-140）、血管性假性血友病因子（vwF：Ag）、血栓调节蛋白（TM）、D-二聚体（DD）、抗凝血酶-Ⅲ（AT—III）变化，并探讨葛根素对AP的治疗作用。方法AP患者78例，重型AP（SAP）26例，轻型AP（MAP）52例；采用随机数字表法分为葛根素治疗组40例及常规治疗组38例。两组均给予禁食，持续胃肠减压，纠正水电解质及酸碱平衡紊乱，静脉支持，抑酸药物，抗生素抑制胰酶分泌及抑制胰酶活性的药物等综合治疗，葛根素组联合葛根素注射液0．5g加入5％葡萄糖注射液500ml静脉滴注，每日1次。治疗前后应用ELISA法测定两组患者血栓前状态分子标志物GMP-140、vwF：Ag、TM、DD，采用发色底物法测定AT．Ⅲ活性、血尿淀粉酶，选择同期健康体检者22名为健康对照组。结果SAP患者血浆GMP-140为（86．26±15．28）ng／L、vwF为（236．22±31．78）％、TM为（65．70±12．27）μ/L、DD为（0．87±0．04）mg／L，血浆AT—In为（56．13±15．78）U／ml，与MAP组[（58．68±15．86）ng／L、（126．68±17．06）％、（9．80±6．98）斗g／L、（0．56±0．05）mg／L、（80．38±18．29）U／m1]和健康对照组[（32．56±18．17）ng／L、（95．12±31．68）％、（4．26±0．92）μ/L、（0．36±0．06）mg／L、（98．76±22．68）U／m1]比较，差异均有统计学意义（P均〈0．01）。葛根素组治疗后血浆GMP-140为（31．52±15．81）ng／L、vwF为（93．32±28．62）％、TM为（4．36±0．82）μ/L、DD为（0．32±O．05）mg／L，较常规治疗组[（59．62±13．73）ng／L、（128．81±16．23）％、（11．23±7．62）μg／L、（0．68±0．04）mg／L]明显下降（t值分别为-23．283、-28．205、-43．419、-15．642，P均〈0．001），葛根素组血浆AT-Ⅲ[（97．68±21．69）U／m1]较常规治疗组[（76．86±17．92）U／m1]明显上升，差异有统计学意义（t=14．967，P〈0．01）；血、尿淀粉酶和腹痛缓解时问[（81．26±17．12）U／L、（416．37±116．50）U／L、（2．18±0．76）d]与常规治疗组[（119．63±51．87）U／L、（576．32±126．58）U／L、（5．26±0．58）d]比较差异均有统计学意义（t值分别为-7．618、-36．659、-13．619，P均〈0．001）。结论血栓前状态分子标志物异常变化可能是AP发生、发展的主要因素之一。葛根素具有改善胰腺微循环和调节血栓前状态分子标志物的作用，对AP有一定治疗作用。

Objective To study changes of molecular markers of prothrombotic state ： Platelet granule membrane protein （ GMP-140）, Von Willebrand factor （ vWF ： Ag）, thrombomodulin （ TM）, Two-D dimer （ DD）, antithrombin III （ AT- llI） in plasma and puerarin for treatment functions of acute pancreatitis （AP）. Methods In 78 patients with AP [ severe acute pancreatitis（SAP） ：26 cases, mild acute pancreatitis （MAP） ：52 cases ], using a random number table, the patients were given puerarin treated base （ n = 40） and conventional treated base group （ n = 38 ） . The two groups were given fast, continuous gastrointestinal decompression, correction of electrolyte and acid-base balance disorders, vein support, antisecretory drugs, antibiotics inhibit pancreatic secretion and inhibition of trypsin activity of drug treatment. Puerarin group： Puerarin injection 0.5 g in 5% glucose injection intravenous infusion of 500 ml, 1 time a day. GMP-140 vWF：Ag, TM, DD were measured by the methods of analysis of enzyme-linked immunosorbent assay and AT-HI was measured by the methods of analysis of chromogenic substrate method preformed in all patients,plasma amylase and uric amylase were determined by the method of somogyi and after the treatment. And 22 healthy people were selected as normal controls （ NC, Group C,n = 22）. Results Compared with the Group C and MAP, the plasma GMP-140 [ （86. 26 ＋ 15.28 ） ng/Lvs （32.56 ＋ 18.17） ng/L and （58.68 ~ 15.86）ng/L],vWF[（236.22 ~31.78）%vs （95. 12 2 31.68）% and （126.68~17.06）%1,TM [（65.70 212.27）μg/L vs （4.26 ~0.92）txg/L and （9.80 2 6. 98） I^g/L] ,DD [ （0. 87 20. 04） mg/L vs （0. 36 20.06） mg/L and （0. 56 20. 05） mg/L] were significantly elevated, however the AT- IU [ （56. 13 ＋ 15. 78 ） U/ml vs （ 98.76 2 22. 68 ） U/ml and （ 80. 38 2 18.29 ） U/ml ） was significantly decreased SAP （ P 〈 0. 01 ）. There were significant differences on the levels of GMP-140 [（31.52 215.81）ng/L vs （59.62 ~ 13.73）ng/L,t = -23.283~,vWF[（93.32 228.62）% vs （128.81 2 16.23）% ,t= -28.205,P〈0.01 ] ,TM[ （4.36 2 0. 82） p^g/L vs （11.23 2 7. 62） i^g/L,t = -43.419,P 〈 0.001],DD[（0.32＋0.05）mg/L vs （0.68 20.04）mg/L,t = -15.642,P〈0.001] ,AT-11I（（97.68 2 21.69） U/ml vs （ 76. 86 ~ 17.92 ） U/m, t = 14. 967, P 〈 0.01 ） between puerarin treated base group and conventional treated base group. Comparing with treated base, the group given puerarin obviously shortened the increased of plasma [ （81.26 ~ 17. 12 ）U/L vs （ 119. 63 ＋ 51.87 ） U/L, t = -7. 618, P 〈 0. 001 ], uric amylase [ （416. 37 ＋ 116. 50） U/L vs （ 576. 32 2 126. 58 ） U/L, t = - 36. 659, P 〈 0. 001 ], the time of abdominal pain relief and therapy to spend [ （2. 18 2 0. 76 ） d vs （ 5.26 2 0. 58 ） d , t = - 13. 619, P 〈 0. 001 ]. Conclusion The molecular markers of prothrombotie state ： GMP-140, vWF： Ag, TM, DD, AT- HI might all play key roles in the development of AP. Puerarin can improve the pancreatic microeirculation and adjust molecular markers of prothrombotic state, and had certain treatment functions with AP.