观察替米沙坦对高血压大鼠动脉血管平滑肌细胞内质网应激相关因子葡萄糖调节蛋白94(GRP94)和C/EBP同源蛋白(CHOP)的表达,以及血管中层厚度的变化的影响.将48只成年雄性SD大鼠随机等分为假手术对照组(对照组)、手术模型组和替米沙坦组.对照组分离腹主动脉,但不行狭窄术；模型组行腹主动脉狭窄术(TAC)；替米沙坦组行腹主动脉狭窄术并给予每天替米沙坦1.5 mg/kg.喂养6周用颈动脉插管法测定各组大鼠的动脉压(MAP)；利用图像分析软件测量血管中层的厚度.用免疫组织化学法和western-blot法检测GRP94和CHOP的表达水平.结果:①手术模型组大鼠的MAP显著高于相应的对照组和替米沙坦组,有统计学意义(P＜0.05).②手术模型组的GRP94表达量高于对照组和替米沙坦组,有统计学意义(P＜0.05).③手术模型组的CHOP蛋白表达量高于对照组和替米沙坦组,有统计学意义(P＜0.05).④手术模型组大鼠血管平滑肌中层厚度厚于对照组和替米沙坦组,有统计学意义(P＜0.05).说明腹主动脉狭窄致高血压可引起血管平滑肌细胞内质网应激反应,导致GRP94表达及CHOP表达的增加.替米沙坦可能通过减轻内质网应激,逆转高血压所致的血管平滑肌细胞的损伤作用,对血管平滑肌细胞有保护作用.%To observe the effects of telmisartan on the expression of glucose-regulated protein 94(GRP94) and C/EBP-homologous protein( CHOP) and the vascular changes in the thickness of the middle, 48 adult male SD rats were randomly divided into sham operation group (control group), model group and the telmisartan group. The rats in model group received abdominal TAC,The rats in telmisartan group received abdominal TAC and give 1. 5 mg/kg daily telmisartan. Six weeks later, the MBP and HR were measured through carotid artery incubation ,the aortic media thickness was measured by image analyses software. The expression of GRP94 and CHOP in the vascular smooth muscle cells were examined by westem-blot and immunohistochemistry. It is resulted that: (1)The MAP of model group rats was significantly higher than the corresponding control group and the telmisartan group rats, there was statistically significant (P < 0.05): (2)The expression of GRP94 and CHOP of model group rats were significantly higher than the corresponding control group and the telmisartan group rats , there was statistically significant (P <0. 05) : (3)The aortic media thickness of model group rats were significantly thicker than the corresponding control group and the telmisartan group rats ,there was statistically significant (p<0. 05). It is conclusied that: high blood pressure results from abdominal aortic stenosis can cause endoplasmic reticulum stress response of vascular smooth muscle cell. Telmisartan may exerts an protective effect on vascular smooth muscle cell by inhibiting the endoplasmic retieulum stress via down-regulating the expression of GRP94 and CHOP.
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