目的：观察高同型半胱氨酸（hyperhomocysteine，Hcy）对高血压大鼠心肌内质网应激（endoplasmic reticulum stress，ERS）相关因子GRP78和CHOP表达的影响，并探讨HHcy与左室肥厚的关系。方法采用腹主动脉缩窄术制备高血压大鼠模型，术后2周用无创大鼠尾动脉测压仪测大鼠尾动脉压，择取40只高血压大鼠，随机分为对照组和高蛋氨酸组，每组20只。对照组给予普通饮食，高蛋氨酸组给于含2%蛋氨酸饮食。按分组后饲养时间不同，分别又将各组大鼠分为4W亚组及8W亚组，每组10只。无创大鼠尾动脉测压仪检测动脉收缩压（SBP），同型半胱氨酸Hcy检测仪测血清Hcy浓度、称取体重、全心质量及左心室质量计算大鼠心肌肥厚指数HWI及LVWI，通过HE染色观察心肌细胞形态学改变，免疫组化和western检测大鼠心肌组织中GRP78及CHOP表达水平。结果①对照组大鼠血清Hcy水平无明显增高，随时间延长，高蛋氨酸组大鼠血清Hcy水平增高且显著高于对照组（P＜0.01）。②对照组与高蛋氨酸组大鼠SBP值随时间的增长而升高。两组4W亚组间相比，高蛋氨酸组大鼠SBP略高于对照组，但两组间SBP值无统计学差异（P＞0.05）；两组8W亚组间相比，高蛋氨酸组大鼠SBP值明显高于对照组（P＜0.05）。③对照组与高蛋氨酸组4W、8W亚组大鼠HWI及LVWI均有明显增高，且高蛋氨酸组相应亚组大鼠HWI及LVWI增高更为明显（P＜0.05）。④4W时，高蛋氨酸组大鼠心肌细胞GRP78表达明显高于对照组（P＜0.05）；8W时，高蛋氨酸组大鼠心肌细胞CHOP表达较对照组增高更为显著（P＜0.05）。结论血清高Hcy浓度可促使心肌细胞ERS加重，导致ERS相关因子GRP78及CHOP表达失衡，促凋亡因子CHOP表达占优势，导致左室肥厚程度加重。ERS可能是高Hcy加重高血压左室肥厚的分子生物学机制之一。%Objective To observe the influences of hyperhomocysteine (Hcy) on expressions of myocardial GRP78 and CHOP (relative factors to endoplasmic reticulum stress, ERS), and discuss the relationship between Hcy and left ventricular hypertrophy. Methods The rat model of hypertension was established by using abdominal aortic coarctation and after 2 w, caudal artery pressure was detected with non-invasive caudal artery piezometer and 40 hypertensive rats were randomly divided into control group and homomethionine group (Hmn group, each n=20). Control group was given normal diet and Hmn group was given diet with 2%methionine. According to feeding time after grouping, the two groups were further divided into 4-w Hmn or control subgroups and 8-w Hmn or control subgroups respectively (each n=10). The level of SBP was detected by using non-invasive caudal artery piezometer, concentreation of plasma Hcy was detected by using Hcy detector, and heart weight index (HWI) and left ventricular weight index (LVWI) were calculated after weighing body weight, heart weight and left ventricular weight. The changes of cardiomyocyte morphology were observed after HE staining, and expressions of GRP78 and CHOP were detected by using immunohistochemistry technique. Results ①Hcy level did not increased in control group and increased gradually in Hmn group, and was significantly higher in Hmn group than that in control group (P<0.01). ②The level of SBP increased in two groups with the time. The comparison between 4-w Hmn or control subgroups showed that SBP was higher in 4-w Hmn group than that in 4-w control group but the different was not statistically significant (P>0.05). The comparison between 8-w Hmn or control subgroups showed that SBP was significantly higher in 8-w Hmn group than that in 8-w control group (P<0.05). ③HWI and LVWI increased significantly in 4-w and 8-w Hmn or control subgroups, which was more significant in 4-w and 8-w Hmn subgroups (P<0.05). ④The expression of GRP78 was significantly higher in Hmn group than that in control group (P<0.05) on the 4th w, and expression of CHOP was much significantly higher in Hmn group than that in control group (P<0.05) on the 8th w. Conclusion Higher level of serum Hcy can exacerbate cardiomyocyte ERS and induce disorder of GRP78 and CHOP expressions. When CHOP expression is dominant, left ventricular hypertrophy will be exacerbated. ERS may be one of molecular biomechanisms of higher Hcy exacerbating left ventricular hypertrophy.
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