Kusnierz-Cabala Beata, Gurda-Duda Anna, Solnica Bogdan, Fedak Danuta, Dumnicka Paulina, Panek Jozefa, Kulig Jan
Department of Diagnostics, Chair of Clinical Biochemistry, Jagiellonian University Medical College, Kopernika 15A, 31-501 Krakow, Poland.
Clin Lab. 2011;57(11-12):999-1006.
Acute pancreatitis (AP) causes an increase in proinflammatory cytokine and acute phase protein levels. Our previous studies in AP showed the role of fetuin A as a negative acute phase protein. Matrix Gla protein (MGP), beside fetuin A, is one of the main inhibitors of extraosseous calcification. In the present preliminary study we evaluated the relationship between MGP, lipase, and inflammation in AP patients.
The study included 40 patients with AP of diverse severity (28 mild, 12 severe), assessed during the early phase of AP (day 1 - day 7 of hospitalization). The concentration of MGP, fetuin A, polymorphonuclear elastase (PMN-elastase), interleukin 6 (IL-6), interleukin 18 (IL-18), hepatocyte growth factor (HGF), high sensitivity tumor necrosis factor alpha (hs TNFalpha), soluble receptor of tumor necrosis factor II (sTNFRII), and neopterin were measured by ELISA kits; albumin, lipase and amylase were measured on a Modular P Chemistry Analyser (Roche Diagnostica, Germany); procalcitonin (PCT) was measured using the LUMItest PCT (Brahms, Germany), and serum amyloid A (SAA) and high sensitivity C-reactive protein (hs CRP) were measured using an immunonephelometric method on a Nephelometer BNII (Siemens Healthcare, Germany).
MGP positively correlated with lipase activity (R = 0.64; p < 0.05) on day 1 after admission to hospital. Lower MGP levels were consistent with higher intensity of inflammation, as MGP significantly (p < 0.05) inversely correlated with IL-6 (R = -0.48 on day 3; R = -0.46 on day 5 and R = -0.52 on day 7 after admission), IL-18 (R = - 0.55; R = -0.60; R = -0.48 on day 1, day 3, and day 5, respectively), HGF (R = -0.58 on day 3), hs TNFalpha (R = -0.45 on day 1 and R = -0.64 on day 5), its soluble receptor sTNFRII (R = -0.63; R = -0.61; R = -0.59 on day 3, day 5, and day 7, respectively), hs CRP (R = -0.76 on day 1 and R = -0.83 on day 5), PCT (R = -0.62 on day 1 and R = -0.59 on day 7), SAA (R = -0.45 on day 5) as well as with neopterin (R = -0.52 on day 1 after admission). MGP levels dropped simultaneously with fetuin A (R = 0.50 on day 3; R = 0.60 on day 5 and R = 0.63 on day 7) and albumin concentrations (R = 0.51; R = 0.70; R = 0.94 on day 1, day 5, and day 7 day after admission, respectively). There was a relationship between lipase activity and MGP concentration on day 1 of hospitalization (R = 0.64; p < 0.05).
Our preliminary results indicate that the MGP level correlated negatively with all of the proinflammatory cytokines and acute phase proteins studied in patients with AP, and positively with lipase, fetuin A, and albumin measurements. These findings may indicate the role of MGP in calcium and phosphate metabolism disturbances in the course of AP.
急性胰腺炎(AP)会导致促炎细胞因子和急性期蛋白水平升高。我们之前对AP的研究表明胎球蛋白A作为一种负急性期蛋白发挥作用。除胎球蛋白A外,基质Gla蛋白(MGP)是骨外钙化的主要抑制剂之一。在本初步研究中,我们评估了AP患者中MGP、脂肪酶和炎症之间的关系。
该研究纳入了40例不同严重程度的AP患者(28例轻度,12例重度),在AP早期(住院第1天至第7天)进行评估。采用ELISA试剂盒检测MGP、胎球蛋白A、多形核弹性蛋白酶(PMN - 弹性蛋白酶)、白细胞介素6(IL - 6)、白细胞介素18(IL - 18)、肝细胞生长因子(HGF)、高敏肿瘤坏死因子α(hs TNFα)、肿瘤坏死因子II可溶性受体(sTNFRII)和新蝶呤的浓度;使用Modular P化学分析仪(德国罗氏诊断公司)检测白蛋白、脂肪酶和淀粉酶;使用LUMItest PCT(德国布拉姆斯公司)检测降钙素原(PCT),并使用免疫比浊法在Nephelometer BNII(德国西门子医疗公司)上检测血清淀粉样蛋白A(SAA)和高敏C反应蛋白(hs CRP)。
入院后第1天,MGP与脂肪酶活性呈正相关(R = 0.64;p < 0.05)。较低的MGP水平与较高的炎症强度一致,因为MGP与IL - 6(入院后第3天R = -0.48;第5天R = -0.46;第7天R = -0.52)、IL - 18(第1天、第3天和第5天分别为R = - 0.55;R = -0.60;R = -0.48)、HGF(第3天R = -0.58)、hs TNFα(第1天R = -0.45,第5天R = -0.64)、其可溶性受体sTNFRII(第3天、第5天和第7天分别为R = -0.63;R = -0.61;R = -0.59)、hs CRP(第1天R = -0.76,第5天R = -0.83)、PCT(第1天R = -0.62,第7天R = -0.59)、SAA(第5天R = -0.45)以及新蝶呤(入院后第1天R = -0.52)均显著负相关(p < 0.05)。MGP水平与胎球蛋白A(第3天R = 0.50;第5天R = 0.60;第7天R = 0.63)和白蛋白浓度(入院后第1天、第5天和第7天分别为R = 0.51;R = 0.70;R = 0.94)同时下降。住院第1天脂肪酶活性与MGP浓度之间存在相关性(R = 0.64;p < 0.05)。
我们的初步结果表明,AP患者中MGP水平与所研究的所有促炎细胞因子和急性期蛋白均呈负相关,与脂肪酶、胎球蛋白A和白蛋白测量值呈正相关。这些发现可能表明MGP在AP病程中钙和磷代谢紊乱中发挥作用。