下肢静脉高压大鼠后肢皮肤病变的组织学研究

Histological study of pathological tissues in the lower extremity venous hypertension rats

目的探讨下肢静脉高压大鼠皮肤病变的生物分子学机制。方法通过建立合适的下肢静脉高压大鼠模型来观察大鼠后肢病变组织的组织学改变。将36只大鼠随机分成4组,A组为下肢静脉高压+舒洛地特组,B组为下肢静脉高压+生理盐水组,C组为单纯下肢静脉高压组,D组为正常对照组。A、B组分别腹腔注射舒洛地特和生理盐水2周,1周、2周、2个月后分别检测大鼠后肢组织中血管细胞黏附分子-1(VCAM-1)、细胞间黏附分子-1(ICAM-1)、肿瘤坏死因子-α(TNF-α)和内皮一氧化氮合酶(eNOS)表达情况。结果免疫组化结果显示B、C组VCAM-1、ICAM-1、TNF-α阳性表达量逐渐增加,eNOS阳性表达量逐渐减低,和正常组比较差异有统计学意义(P<0.05),B、C组间差异无统计学意义(P>0.05)。A组VCAM-1、ICAM-1、TNF-α阳性表达量逐渐降低,eNOS阳性表达量逐渐增加,和B组间差异有统计学意义(P<0.05),2个月时和正常组比较差异无统计学意义(P>0.05)。结论下肢静脉高压时存在血管内皮损伤,VCAM-1、ICAM-1、TNF-α表达增加,eNOS表达降低;舒洛地特可以有效改善并修复损伤的血管内皮,调节VCAM-1、ICAM-1、TNF-α、eNOS的表达水平。

Objective To investigate the molecular mechanism of skin lesions in rats with lower extremity venous hypertension. Methods The histological changes of the pathological tissues of the hind limbs of rats were observed by establishing a suitable rat model of venous hypertension of the lower limbs. 36 rats were divided into four groups randomly, including lower extremity venous hypertension + sulodexide group (Group A), lower extremity venous hypertension + normal saline group (Group B), simple lower extremity venous hypertension group (Group C), normal control group (Group D). The expressions of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α(TNF-α) and endothelial nitric oxide synthase (eNOS) in the hind limb tissues of rats one week, two weeks and two months after intraperitoneal injection of sulodexide and normal saline were detected. Results The immunohistochemical results showed that the positive expression levels of VCAM-1、ICAM-1 and TNF-α in group B and group C increased gradually and the positive expression levels of eNOS decreased gradually with the extension of time, and the differences between two groups and normal control group were statistically significant (P<0.05), while the differences between group B and group C were not statistically significant (P>0.05). The positive expression levels of VCAM-1、ICAM-1 and TNF-αin group A decreased gradually, and the positive expression levels of eNOS increased gradually. The difference with group B was statistically significant (P<0.05), while there were no significant difference between group A and group D at two months (P>0.05). Conclusion Vascular endothelial injury is found in the lower extremity venous hypertension. The expression of VCAM-1、ICAM-1 and TNF-α increased, and the expression of eNOS decreased. Sulodexide can effectively improve and repair damaged vascular endothelium and regulate the expression of VCAM-1、ICAM-1 and TNF-α.