老龄大鼠脑缺血-再灌注微血管基底膜损伤变化及与纤溶酶原激活系的关系

目的研究老龄大鼠脑缺血再灌注(I/R)不同时期微血管基底膜损伤与纤溶酶原激活系的关系。方法采用大脑中动脉阻塞(MCAO)线栓法制备大鼠局灶性脑I/R模型,将大鼠分为青年假手术组、老龄假手术组、青年模型组和老龄模型组,其中模型组又分为I3h,I/R6、12、24、72和144h各时间点组。采用免疫组化、酶谱与反向酶谱分析等方法测定各脑微血管结构、基底膜型胶原、层连蛋白(LN)和纤溶酶原激活系的变化。结果与青年假手术组比较,老龄假手术组型胶原、LN表达增强。随着I/R时间的延长,老龄与青年大鼠基底膜成分型胶原和LN表达递减;组织型纤溶酶原激活剂(tPA)、尿激酶型纤溶酶原激活剂(uPA)、纤溶酶原激活物抑制剂(PAI1)表达水平呈先增强后降低的趋势。与青年模型组相同时间点比较,老龄模型组型胶原(I3h、I/R6h、I/R12h)、LN(I3h、I/R6h^24h)、tPA(I/R6h^24h)、uPA(I/R12h^144h)表达增强,PAI1(I/R12h、I/R24h)表达降低,差异均有显著性。另外,PAI1的反向酶谱分析比较,量的变化与免疫表达规律基本一致。结论随着增龄,大鼠脑微血管基底膜成分型胶原、LN增加。在脑I/R微血管基底膜损伤方面,老龄大鼠较青年严重,其损伤的特点与纤溶酶原激活系变化有关。

脑脉通对老龄大鼠脑缺血/再灌注纤溶酶原激活系调节作用的影响

目的研究脑脉通对老龄大鼠脑缺血/再灌注(I/R)纤溶酶原激活系调节作用的影响。方法采用线栓法复制局灶性脑I/R模型,将老龄大鼠分为假手术组、模型组、脑脉通组、尼莫地平组,后三组又分为脑缺血3 h和I/R 6、12、24 h、3、6 d组。采用电镜、免疫组化和酶谱分析等法,观察各组脑微血管结构、纤溶酶原激活系的变化。结果与假手术组比较,模型组脑微血管病理损伤明显,t-PA(I 3 h^I/R 6 d)、u-PA(I/R12 h^6 d)、PAI-1(I/R 6 h^3 d)表达水平显著增强。与模型组比较,脑脉通组微血管病理损伤明显改善,t-PA(I/R 6 h^3 d)、u-PA(I/R 12 h^3 d)的蛋白表达显著降低和PAI-1(I/R 12 h^3 d)的蛋白表达显著增强。各组PAI-1的酶谱分析比较,其量的变化与免疫表达结果基本一致。结论脑脉通对老龄大鼠脑I/R微血管基底膜损伤的保护作用与其对纤溶酶原激活系调节有关。

Clinical Research on the Changes of Plasma TFPI and uPA System in Malignant Tumor

Objective: To investigate the expression levels and significance of TFPI, uPA, uPAR and PAI in malignant patients. Methods: The levels of TFPI, uPA and uPAR were measured by using ELISA and the level of PAI was determined by method of chromogenic substrates in 44 patients with malignant solid tumors (group A1) and 30 patients with acute leukemia (AL, group A2). Results: The levels of TFPI, uPA, and uPAR in group A1 were higher than those in normal control group (group B). TFPI, uPAR levels in group A2 were higher than those in group B, while the level of PAI in group A2 was lower than that in group B. Among the groups, TFPI was increased in the combined infection group; PAI decreased in the hemorrhage group; TFPI, uPA, uPAR and PAI increased in relapsing and metastasis group; TFPI decreased in one-week dead group, while uPA and uPAR increased. Conclusion: The patients with malignant solid tumor and AL had different anticoagulation or fibrinolysis states. TFPI, uPA, Upar and PAI can be used to evaluate the disease condition and the prognosis.