Ouyang Lin, Peng Youming, Wu Guobao, Xu Xiangqing, He Zhihui
Intensive Care Unit, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2013 May;38(5):458-67. doi: 10.3969/j.issn.1672-7347.2013.05.004.
To investigate the effect of plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (t-PA), and endothelin-1 (ET-1) on the atherosclerosis progress in the maintenance hemodialysis patients.
We enrolled 19 patients with maintenance hemodialysis (MHD) and 11 healthy people as control. Patients were divided into 2 groups according to their age above or below 40 years old (11 and 8 in each, respectively), whereas the subjects in control group were below 40 years old. All the clinical information of the research subjects was collected: including age, gender, time of hemodialysis, blood pressure, blood urea nitrogen (BUN), and serum creatinine (SCr). Immunohistochemistry and pathological image analysis were used to investigate the pathological changes, calcification and the expression of PAI-1, t-PA, and ET-1 on the blood vessel.
Compared with the age-matched healthy control group, there were higher blood vascular media thickness, blood vascular media thickness/diagmeter ratio, blood vascular media thickness area/vascular inter-wall area ratio (P<0.05) and more calcification (P<0.05) in the the internal iliac artery in the chronic renal failure MHD patients. All the results were similar when compared the above 40 years old group with the below 40 years old one in the chronic renal failure MHD patients. There were positive correlation of blood vascular media thickness with age and blood pressure (P<0.05). Expression of PAI-1, ET-1, t-PA on the internal iliac artery vessel was elevated in the chronic renal failure MHD patients compared with the health control (P<0.05). The level of PAI-1 or ET-1 was much higher in the above 40 years old group than the below 40 years old one in the chronic renal failure MHD patients, whereas there was no significant difference in the t-PA expression between the 2 groups (P<0.05). There were positive correlation of PAI-1 or ET-1 expression with age and blood pressure (P<0.05). There were positive correlation of PAI-1 or ET-1 expression with blood vascular media thickness and calcification (P<0.05 or P<0.01). There was no correlation of hemodialysis time with blood vascular media thickness, calcification, PAI-1, t-PA, or ET-1 expressions.
MHD patients accompany with atherosclerosis which is severer in the patients above 40 years old than the patients below 40 years old. The higher of the blood pressure, the severer of the atherosclerosis. Abnormal expression of PAI-1 plays an important role in the progress of the atherosclerosis in the chronic renal failure MHD patients, whereas t-PA has no function in this process. The level of PAI-1 and ET-1 would be helpful to evaluating the degree of atherosclerosis in the chronic renal failure MHD patients. Hemodialysis time may not be a potential accelerator for atherosclerosis progression.
探讨纤溶酶原激活物抑制剂-1(PAI-1)、组织型纤溶酶原激活物(t-PA)和内皮素-1(ET-1)对维持性血液透析患者动脉粥样硬化进展的影响。
选取19例维持性血液透析(MHD)患者和11名健康人作为对照。患者按年龄40岁及以上或40岁以下分为2组(每组分别为11例和8例),对照组均为40岁以下。收集研究对象的所有临床资料:包括年龄、性别、透析时间、血压、血尿素氮(BUN)和血清肌酐(SCr)。采用免疫组织化学和病理图像分析方法,研究血管的病理变化、钙化情况以及PAI-1、t-PA和ET-1的表达。
与年龄匹配的健康对照组相比,慢性肾衰竭MHD患者髂内动脉的血管中膜厚度、血管中膜厚度/管径比值、血管中膜厚度面积/血管壁间面积比值更高(P<0.05),钙化更严重(P<0.05)。在慢性肾衰竭MHD患者中,40岁及以上组与40岁以下组比较,上述结果相似。血管中膜厚度与年龄和血压呈正相关(P<0.05)。与健康对照组相比,慢性肾衰竭MHD患者髂内动脉血管中PAI-1、ET-1、t-PA的表达升高(P<0.05)。在慢性肾衰竭MHD患者中,40岁及以上组的PAI-1或ET-1水平远高于40岁以下组,而两组t-PA表达无显著差异(P<0.05)。PAI-1或ET-1表达与年龄和血压呈正相关(P<0.05)。PAI-1或ET-1表达与血管中膜厚度和钙化呈正相关(P<0.05或P<0.01)。透析时间与血管中膜厚度、钙化、PAI-1、t-PA或ET-1表达无相关性。
MHD患者伴有动脉粥样硬化,40岁及以上患者比40岁以下患者更严重。血压越高,动脉粥样硬化越严重。PAI-1的异常表达在慢性肾衰竭MHD患者动脉粥样硬化进展中起重要作用,而t-PA在此过程中无作用。PAI-1和ET-1水平有助于评估慢性肾衰竭MHD患者动脉粥样硬化程度。透析时间可能不是动脉粥样硬化进展的潜在促进因素。