马来酸依那普利叶酸对H型高血压大鼠血管平滑肌细胞GRP94和caspase-12的表达影响

目的 观察同型半胱氨酸（Homocysteine,Hcy）对自发性高血压（SHR）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）和半胱氨酸门冬氨酸特异性蛋白酶12（caspase-12）表达变化的影响及马来酸依那普利叶酸片对其的干预机制.方法 将36只成年雄性SHR大鼠随机等分为3组,即对照组、蛋氨酸组和依叶片（马来酸依那普利叶酸片）组,每组12只.喂养8周后检测血清Hcy浓度,测定平均动脉压（MAP）,测量主动脉中层的厚度;检测CRP94和caspase-12的表达水平.结果 蛋氨酸组与对照组相比,MAP无差异（P＆gt;0.05）,血清Hcy浓度明显增高（P〈0.01）,主动脉中层厚度、CRP94和caspase-12蛋白表达量显著增加（P〈0.05）;依叶片组与蛋氨酸组相比,血清Hcy明显降低（P〈0.01）,MAP、血管平滑肌中层厚度、CRP94和caspase-12蛋白表达量显著降低（P〈0.05）.结论 高Hcy可加重高血压动脉血管平滑肌细胞内质网应激反应,导致CRP94表达增加及caspase-12的活化增高,从而加重血管损伤,导致血管重构;马来酸依那普利叶酸片可能通过下调血浆Hcy浓度和降低血压来抑制内质网应激,从而逆转Hcy对高血压血管平滑肌细胞的损伤作用.

Effects of Enalapril Maleate and Folic Acid on Expressions of the GRP94 and Caspase-12 in Vascular Smooth Muscle Cells of H-hypertensive Rats

Objective To observe the effect of homocysteine （Hcy） on expressions of GRP94 （glucose regula- ted protein, GRP94） and caspase-12 （cysteine-containing aspartate-speeific proteases, caspase-12） in vascular smooth muscle endocytoplasmic reticulum of spontaneously hypertensive （SHR） rats, and the intervention mechanism of enalapril maleate and folic acid tablets （EMFA）. Methods Thirty-six adult male SHR rats were randomly divided into control group （n = 12）, Methionine group （n = 12） and EMFA group （n = 12）. Serous Hcy concentration, mean arterial pres- sure （MAP） and aortic media thickness in the three group were detected after 8 weeks of treatment; expression levels of GRP94 and caspase-12 were also detected. Results Compared with those in control group, in Methionine group, MAP showed no significant difference （ P 〉 0.05 ） , serous Hcy concentration was significantly increased （P 〈 0.01 ） , aortic media thickness, expression levels of CRP94 and caspase-12 protein were significantly increased （P 〈 0. 05 ） ; compared with those in Methionine group, in EMFA group, serous Hcy concentration was significantly decreased （P 〈0.01 ）, and MAP, media thickness of vascular smooth muscle, protein expression levels of CRP94 and caspase-12 were significantly decreased （P 〈 0. 05）. Conclusion High hcy can aggravate the stress response of vascular smooth muscle endoplasmic reticulum in hypertension arterial smooth muscle cells, increase CRP94 expression and caspase-12 activation, which may lead to vascular injury exacerbation and vascular remodeling; enalapril maleate and folic acid tablets may invert Hcy effect on the hypertension arterial smooth muscle cells, of cell damage by decreasing serous Hcy and blood pressure to in- hibit endoplasmie reticulum stress response.