普罗布考对糖尿病大鼠大血管病变的影响

Effects of probucol on macro-vasculopathy of diabetic rats

目的探讨普罗布考对糖尿病大鼠大血管病变的影响及机制。方法44只健康Sprague Dawley（SD）雄性大鼠随机分为对照组（NC组，n=8）、糖尿病组（DM组，n=18）、普罗布考干预组（PB组，n=18）3组，四氧嘧啶50mg／kg行尾静脉注射制备糖尿病大鼠模型。糖尿病造模成功后PB组给予普罗布考170mg／（kg·d）灌胃3周，于第4周末处死动物。处死前测定血糖、血脂和体重变化，以及血清丙二醛（MDA）、超氧化物歧化酶（SOD）、全血过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH—PX）。观察主动脉组织形态学改变，并用免疫组织化学法测定主动脉单核细胞趋化蛋白-1（MCP-1）、血管内皮细胞的细胞问黏附分子-1（ICAM-1）的蛋白表达。结果（1）与NC组比较，DM组的体重、血糖、低密度脂蛋白-胆固醇（LDL-C）水平明显升高（P〈0．05）；与DM组相比较，PB组体重增加，血糖、LDL—C水平下降（P〈0．05）。（2）与NC组相比，DM组和PB组大鼠体内MDA和GSH—PX水平明显升高（P〈0．05），SOD／MDA和CAT水平明显下降（P〈0．05）；与DM组比较，PB组MDA水平降低（P〈0．05），SOD／MDA的比值和CAT水平明显升高（P〈0．05）。（3）DM组大鼠主动脉内皮细胞脱落导致内膜不完整，内膜下炎性反应细胞浸润，中层平滑肌细胞增生伴紊乱；对照组未见上述变化；PB组上述变化明显减轻。（4）NC组MCP-1和ICAM-1表达弱，DM组表达呈强阳性，PB组表达较DM组减弱。结论普罗布考可以改善糖尿病大鼠的大血管病变，机制与其降低氧化应激和LDL-C水平有关。

Objective To investigate the intervention and mechanism of probucol for macro-vascu- lopathy of diabetic rats. Methods Forty-four healthy Sprauge-Dawley （SD） male rats were randomly divided into three groups ： normal control group （ NC group, n = 8 ） , diabetes mellitus group （ DM group, n = 18 ） , prohucol intervention group （PB group, n = 18）. The diabetic rat models made by the vena caudalis were injec- ted with alloxan （50 mg/kg weight）. The rats of PB group were given intragastric administration with probu- col 170 mg/（kg ~ d） for three weeks. At the end of the fourth week, the rats were killed. Before that serum glucose, lipid, weiglt and malodialdehyde （ MDA ）, superoxide dismutase （ SOD ）, catalase （ CAT ）, glutathione peroxidase（GSH-PX） were tested. The architectonic appearance of arota were investigated. The expression of the monocyte chemoattactant protein-1 （ MCP-1 ） and intercellular adhension molecule-1 （ ICAM-I ） were de- tected by immunohistochemical staining. Results （ 1 ） Compared with NC group, the weight, serum glucose and low density lipoprotein-cholesterol （LDL-C） in DM group were much higher（ P 〈 0.05 ）. Compared with DM group, the weight in PB group were higher （P 〈 0.05）, but the serum glucose and LDL-C were lower （P 〈 0.05）. （2）Compared with NC group, the MDA and GSH-PX in DM group and PB group were much higher（P 〈 0.05 ）, but the SOD/MDA and CAT were much lower（P 〈 0.05）. Compared with DM group, the MDA of PB group were much higher（P 〈 0.05） ,but the SOD/MDA and CAT were much lower（ P 〈 0.05 ）. （ 3 ） The endothelial cells of the arota of diabetic rats were desquamated heavily, so that the endomembrane of the arota were not integrated. Therefore, the inflammatory cells were infiltrated under the endomembrance, the smooth muscle cells of the stratum medium were hyperplasia and chaos. There were no change in NC group, while little change in PB group. （4）The expression of MCP-1 and ICAM-1 in NC group were weak, but in DM group were strong. Furthermore, the expression of MCP-1 and ICAM-I in PB group were weaker than that in DM group. Conclusion Probucol can improve the macro-vasculopathy of diabetic rats by reducing the levels of oxidative stress and LDL-C.