摘要
目的观察血管紧张素Ⅱ1型受体（AT1R）拮抗剂替米沙坦（TM）和噻唑烷二酮类（TDZs）药物罗格列酮（RSG）对2型糖尿病（T2DM）大鼠早期动脉粥样硬化形成的影响，并探讨其可能的机制。方法40只雄性SD大鼠随机分为正常对照（NC）组、T2DM组、TM组和RSG组，每组10只。以喂高糖高脂饮食方法建立SD大鼠T2DM模型。T2DM组、TM组、RSG组给予高糖高脂饮食1个月后腹腔注射25mg／kg链脲佐菌素；NC组给予普通饮食，注射枸橼酸缓冲液作为对照。在此基础之上，TM组给予替米沙坦5mg／（kg·d）、RSG组给予马来酸罗格列酮5mg／（kg·d）灌胃喂养，早晚各灌1次；NC、T2DM两组给予生理盐水灌胃。16周后测定各组大鼠总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL）水平与稳态血糖（BG）、稳态胰岛素（PGI）浓度；用免疫组化法检测主动脉血管壁过氧化物酶体增殖物激活受体-γ（PPAR-γ）及血管细胞黏附分子-1（VCAM-1）、细胞黏附分子-1（ICAM-1）表达水平。结果T2DM组、TM组和RSG组TC、TG、LDL—C与BG水平较NC组显著升高（F=17．67～205．32，q=3．61～35．07，P〈0．05），TM组和RSG组的TC、TG、LDL-C与BG水平较T2DM组低，差异有显著性（q=4．58～17．03，P〈0．01）。TM组和RSG组及T2DM组PPAR-γ表达水平明显高于NC组，但TM组和RsG组与T2DM组间无显著差异（P〉0．05）；TM组、RSG组VCAM-1、ICAM-1表达水平明显低于T2DM组（F=27．35～311．66，q=19．42～22．80，P〈0．01），而各检测指标在两药物组中的表达差异无显著性（P〉0．05），T2DM组和RSG组主动脉内皮损伤轻于T2DM组。结论替米沙坦和罗格列酮能增强血管壁PPAR-γ活化，抑制VCAM-1、ICAM-1表达和单核细胞浸润，防止早期AS形成。
Objective To observe the effects of telmisartan （TM） and rosiglitazone （RSG） on early atherogenesis in male rats with type 2 diabetes mellitus （DM） and explore the mechanism. Methods Forty male SD rats were equally randomized to four groups： normal control （NC） group, type 2 DM group, TM group and RSG group. A rat model of DM was created by feeding high glucose and high fat diet. The rats in DM, TM and RSG groups were fed with high fat and high glucose diet for one month, then streptozotocin （25 mg/kg） intraperitoneally, to those in NC group, full diet was offered and citrate buffer injected, then followed by telmisartan 5 mg/（kg· d） for the TM, rosiglitazone 5 mg/（kg · d） for the RSG, and normal saline for the NC, which were given through intragastric asministration. The levels of TC, TG, LDL-C, BG and PGI detected in all the groups 16 weeks later. Immunohistochemistry was used to analyze the expressions of PPAR ）% VCAM-1 and ICAM-1 in the aorta vessel wall. Results Compared with the NC, the levels of TC, TG, LDL-C and BG in the DM, TM and RSG groups increased significantly （F=17 67-205.32;q=3. 61-35.07;P〈0. 01）. The levels of TC, TG, LDL-C and BG in TM and RSG groups were lower than that in DM group （q=4.58-17.03,P〈0. 01）. The expressions of PPAR- γ in DM, TM and RSG groups was manifestly higher than that in the NC group, the difference was significant, but the differences within TM, RSG and DM groups were not significant （P〉0.05）. The expressions of VCAM -1 and ICAM- 1 in TM and RSG groups were lower than that in DM group （F=27.35- 311.66;q=19. 42-22. 80;P〈0. 01）.The endothelial damage of the aorta in TM and RSG groups was less severe than that in DM group. Conclusion Teimisartan and rosiglitazone can activate PPAR-γ and inhibit expressions of VCAM-1, ICAM-1 and infiltration of monocyte, and thus preventing early atherogenesis.
出处
《齐鲁医学杂志》
2010年第1期48-50,52,共4页
Medical Journal of Qilu
关键词
糖尿病
2型
动脉硬化
替米沙坦
罗格列酮
diabetes mellitus,type 2
atherosclerosis
telmisartan
rosiglitazone
