高血压患者纤溶功能受损与胰岛素抵抗

Impaired fibrinolysis and insulin resistance in patients with hypertension.

作者信息

Jeng J R, Sheu W H, Jeng C Y, Huang S H, Shieh S M

机构信息

Division of Cardiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Republic of China, Taiwan.

出版信息

Am J Hypertens. 1996 May;9(5):484-90. doi: 10.1016/0895-7061(95)00442-4.

DOI:10.1016/0895-7061(95)00442-4

PMID:8735180

Abstract

Plasma plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (tPA) antigens and activities were measured in 28 patients with hypertension and 12 normal controls. Steady state plasma glucose (SSPG) concentrations were also determined after an infusion of somatostatin, insulin and glucose. Patients with hypertension were further subdivided into two groups: insulin resistance (SSPG > 190 mg/dL, n = 14) and no insulin resistance (SSPG < 190 mg/dL, n = 14). As compared to normal controls, hypertensive patients, either with or without insulin resistance, had a significant (P < .005) increases in PAI-1 activity (18.6 +/- 1.3 upsilon 8.1 +/- 0.8 IU/mL), PAI-1 antigen (31.1 +/- 2.0 upsilon 12.7 +/- 0.9 ng/mL) and tPA antigen (15.5 +/- 0.9 upsilon 8.8 +/- 0.9 ng/mL), and significant decrease in tPA activity (0.43 +/- 0.05 upsilon 1.02 +/- 0.16 IU/mL) than normotensive controls. Furthermore, hypertensive patients with insulin resistance had significantly higher PAI-1 activity (22.0 +/- 2.2 upsilon 15.3 +/- 0.8 IU/mL, P = .006) and tPA antigen (17.4 +/- 1.2 upsilon 13.6 +/- 1.3 ng/mL, P = .02) than did hypertensive patients without insulin resistance. However, PAI-1 antigen was insignificantly higher (34.1 +/- 2.9 upsilon 28.1 +/- 2.4 ng/mL, P = .06) and tPA activity insignificantly lower (0.42 +/- 0.08 upsilon 0.43 +/- 0.08 IU/mL, P = .47) in hypertensive patients with insulin resistance than in those without insulin resistance. In addition, PAI-1 activity and tPA antigen were significantly correlated with blood pressure, SSPG, triglyceride, HDL-cholesterol and integrated glucose response to an oral load of 75 g glucose. Thus, patients with hypertension have impaired fibrinolytic activity due to increased PAI-1 when compared to normotensive controls, and the magnitude of this fibrinolytic defect is greater in hypertensive patients who have insulin resistance. Insulin resistance with associated metabolic abnormalities may be one of the causes for impaired fibrinolysis in hypertension.

摘要

对28例高血压患者和12名正常对照者测定了血浆纤溶酶原激活物抑制剂1型（PAI-1）、组织纤溶酶原激活物（tPA）的抗原及活性。在输注生长抑素、胰岛素和葡萄糖后还测定了稳态血浆葡萄糖（SSPG）浓度。高血压患者进一步分为两组：胰岛素抵抗组（SSPG>190mg/dL，n=14）和无胰岛素抵抗组（SSPG<190mg/dL，n=14）。与正常对照相比，有或无胰岛素抵抗的高血压患者的PAI-1活性（18.6±1.3对8.1±0.8IU/mL）、PAI-1抗原（31.1±2.0对12.7±0.9ng/mL）和tPA抗原（15.5±0.9对8.8±0.9ng/mL）均显著升高（P<.005），而tPA活性（0.43±0.05对1.02±0.16IU/mL）显著低于血压正常的对照者。此外，有胰岛素抵抗的高血压患者的PAI-1活性（22.0±2.2对15.3±0.8IU/mL，P=.006）和tPA抗原（17.4±1.2对13.6±1.3ng/mL，P=.02）显著高于无胰岛素抵抗的高血压患者。然而，有胰岛素抵抗的高血压患者的PAI-1抗原略高（34.1±2.9对28.1±2.4ng/mL，P=.06），tPA活性略低（0.42±0.08对0.43±0.08IU/mL，P=.47），但差异不显著。此外，PAI-1活性和tPA抗原与血压、SSPG、甘油三酯、高密度脂蛋白胆固醇以及口服75g葡萄糖后的综合血糖反应显著相关。因此，与血压正常的对照者相比，高血压患者由于PAI-1升高导致纤溶活性受损，且这种纤溶缺陷在有胰岛素抵抗的高血压患者中更严重。伴有相关代谢异常的胰岛素抵抗可能是高血压患者纤溶功能受损的原因之一。