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目的研究重组人促红细胞生成素(recombinant human erythropoietin,rhEPO)对糖尿病大鼠血脑屏障(BBB)通透性和内皮屏障抗原(endothelial barrier antigen,EBA)表达的影响。方法 30只雄性SD大鼠分成rhEPO治疗组、糖尿病组和正常对照组。rhEPO治疗组、糖尿病组用链脲霉素(streptozotocin,50 mg/kg)静脉一次性注射制备糖尿病模型。rhEPO治疗组于模型制备同时rhEPO(3 000 U/kg),皮下注射,3次/周,疗程4个月。糖尿病组和正常对照组皮下注射等量生理盐水。4个月后均取额叶皮层。用免疫组织化学(IHC)的方法检测微血管内皮细胞EBA及微血管周围纤维蛋白原(fibrinogen)表达。结果 IHC染色显示rhEPO治疗组、糖尿病组和正常对照组EBA阳性微血管数分别为(10.30±1.17)、(7.30±1.14)和(13.20±1.33),rhEPO治疗组EBA阳性微血管数与正常对照组比较明显减少(P<0.01),而rhEPO治疗组与糖尿病组比较EBA阳性微血管数显著增加(P<0.01);rhEPO治疗组、糖尿病组和正常对照组fibrinogen阳性微血管数分别为(5.52±2.54)、(7.60±3.11)和(1.30±0.46),rhEPO治疗组与糖尿病组比较fibrinogen阳性微血管数显著减少(P<0.01)。结论 rhEPO治疗可明显增加糖尿病大鼠血脑屏障EBA表达,减少fibrinogen外渗,减少BBB通透性,对糖尿病大鼠血脑屏障具有保护作用。
Objective To investigate the effects of recombinant human erythropoietin (rhEPO) on the permeability of the blood-brain barrier (BBB) and the expression of endothelial barrier antigen (EBA) in diabetic rats. Methods Thirty male SD rats were divided into rhEPO treatment group, diabetes control group and normal control group. Diabetic rats were treated with streptozotocin (50 mg / kg) by intravenous injection in the rhEPO-treated and diabetic patients. The rhEPO treatment group was treated with rhEPO (3 000 U / kg) at the same time, subcutaneously and 3 times / week for 4 months. Diabetic group and normal control group were injected subcutaneously with normal saline. 4 months after the frontal cortex are taken. Immunohistochemistry (IHC) was used to detect the expression of EBA and microvascular fibrinogen in microvascular endothelial cells. Results IHC staining showed that the number of positive microvessels in rhEPO-treated group, diabetic group and normal control group were (10.30 ± 1.17), (7.30 ± 1.14) and (13.20 ± 1.33), respectively. The number of EBA positive microvessels in rhEPO-treated group was significantly higher than that in normal control group (P <0.01). The numbers of positive microvessels in rhEPO treatment group and diabetic group were significantly increased (P <0.01). The number of fibrinogen positive microvessels in rhEPO treatment group, diabetic control group and normal control group were (5.52 ± 2.54), (7.60 ± 3.11) and (1.30 ± 0.46) respectively. The number of fibrinogen-positive microvessels in rhEPO-treated group and diabetic group was significantly decreased (P <0.01). Conclusion rhEPO treatment can significantly increase the blood-brain barrier EBA expression in diabetic rats, reduce fibrinogen extravasation, reduce BBB permeability, and protect the blood-brain barrier in diabetic rats.