论文部分内容阅读
目的:观察高同型半胱氨酸对高血压大鼠心肌内质网应激相关因子GRP94、caspase12表达的影响,及依那普利叶酸片(简称依叶片)对其表达的干预作用。方法:30只雄性成年自发性高血压大鼠(SHR),随机分为对照组、模型组和依叶片组,每组10只。对照组给予普通颗粒饲料喂养同时给予双蒸水灌胃,模型组给予含3%蛋氨酸的颗粒饲料喂养同时给予双蒸水灌胃,依叶片组给予含3%蛋氨酸的颗粒饲料喂养同时给予依叶片粉剂20 mg/kg/d灌胃。实验第8周末,用颈动脉插管法测各组大鼠平均动脉压(MAP),同型半胱氨酸检测仪检测血清同型半胱氨酸(homocystein,Hcy)浓度,称取体质量、全心质量及左心室质量计算大鼠心肌肥厚指数HWI及LVEI,通过HE染色观察心肌细胞形态学改变,免疫组化检测大鼠心肌组织中GRP94及caspase12表达水平。结果:①大鼠血清Hcy水平的变化。对照组大鼠血清Hcy值在正常值范围。与对照组相比,模型组大鼠血清Hcy值显著增高(P<0.01);与模型组相比,依叶片组大鼠血清Hcy值明显降低(P<0.01)。②大鼠HWI、LVEI及MAP的变化。模型组大鼠的HWI及LVEI均明显高于对照组(P<0.05);依叶片干预后大鼠的HWI及LVEI均明显降低(P<0.05)。对照组与模型组大鼠的MAP均明显增高,但两组大鼠的MAP差异无统计学意义(P>0.05);与模型组相比,依叶片干预后大鼠的MAP明显降低(P<0.01)。③大鼠心肌细胞内质网应激(endoplasmic reticulum stress,ERS)相关因子GRP94及caspase12表达。对照组及模型组大鼠心肌细胞GRP94及caspase12表达均增高。与对照组相比,模型组大鼠心肌细胞GRP94、caspase12表达增高更为明显(P<0.05)。依叶片干预后大鼠心肌细胞GRP94、caspase12表达明显降低(P<0.05)。结论:高Hcy通过ERS途径使高血压大鼠左室肥厚程度加重;依叶片可有效降低血清Hcy及血压水平,抑制心肌细胞ERS,从而有效逆转左室肥厚,其对左室肥厚干预的分子机制为“H型”高血压的预防及治疗提供了新的理论依据。
Objective: To investigate the effect of hyperhomocysteine on the expression of GRP94 and caspase 12 in hypertensive rats and the effect of enalapril on the expression of folic acid. Methods: Thirty male adult spontaneously hypertensive rats (SHR) were randomly divided into control group, model group and leaf-dependent group, 10 rats in each group. The control group was given ordinary pelleted feed while given double distilled water. The model group was fed with pellet feed containing 3% methionine and double distilled water was given to the rats in the control group. Granules fed with 3% Powder 20 mg / kg / d gavage. At the end of the 8th week, the mean arterial pressure (MAP) of rats in each group was measured by carotid artery cannulation. The homocysteine (Hcy) level was measured by homocysteine detector. Cardiac hypertrophy and left ventricular mass were used to calculate the cardiac hypertrophy index HWI and LVEI. The morphological changes of myocardial cells were observed by HE staining. The expression of GRP94 and caspase 12 in myocardium were detected by immunohistochemistry. Results: ① The change of serum Hcy level in rats. The control group rats serum Hcy values in the normal range. Compared with the control group, the serum Hcy of the model group was significantly increased (P <0.01). Compared with the model group, the serum Hcy level of the model group was significantly decreased (P <0.01). ② rats HWI, LVEI and MAP changes. The HWI and LVEI in the model group were significantly higher than those in the control group (P <0.05). The HWI and LVEI in the model group were significantly decreased (P <0.05). Compared with the model group, the MAP of the control group and the model group was significantly higher (P <0.05), while MAP of the two groups was not significantly different (P> 0.01). ③ The expression of GRP94 and caspase 12 in endoplasmic reticulum stress (ERS) in rat cardiomyocytes. The expression of GRP94 and caspase 12 in control group and model group rats were increased. Compared with the control group, the expression of GRP94 and caspase12 in the model group increased more significantly (P <0.05). The expression of GRP94 and caspase 12 in rat cardiomyocytes was significantly decreased after the intervention of leaves (P <0.05). Conclusion: Hyperhomocysteinemia can increase left ventricular hypertrophy in hypertensive rats via ERS pathway. It can effectively decrease serum Hcy and blood pressure and inhibit ERS in cardiomyocytes, which can effectively reverse left ventricular hypertrophy and its molecular mechanism of intervention in left ventricular hypertrophy It provided a new theoretical basis for the prevention and treatment of “H type” hypertension.