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目的:探讨葡萄籽原花青素(GSP)对肾血管性高血压(RH)大鼠血管重塑的影响。方法:采用两肾一夹法建立RH大鼠模型,并设立假手术组。术后2周,选取鼠尾动脉收缩压升至130mmHg以上的大鼠28只为RH大鼠,随机分为4组:高血压模型组,GSP低剂量治疗组(50mg/kg);GSP高剂量治疗组(200mg/kg)和卡托普利阳性对照治疗组(30mg/kg)。治疗6周后,分别测定各组大鼠尾动脉收缩压,苏木精-伊红染色法染色并观察胸主动脉形态,测量中膜平滑肌层数,中膜厚度(MT),管腔内径(LD)及MT/LD等血管重塑形态学参数。ELISA法测量腹主动脉血管组织中内皮素(ET)的含量,Western blotting法检测腹主动脉血管组织中ERK1/2蛋白的表达水平。结果:治疗6周后,与假手术组比较,高血压模型组大鼠的尾动脉收缩压,MT、MT/LD,ET含量,中膜平滑肌层数,ERK1/2蛋白表达水平明显升高;胸主动脉内膜不完整,中膜平滑肌增多,管壁明显增厚,而LD减小。与高血压模型组相比,GSP低(50mg/kg)、高(200mg/kg)剂量均能降低RH大鼠的尾动脉收缩压、MT和MT/LD,减少ET的含量、中膜平滑肌层数的增多,和ERK1/2的蛋白表达水平,亦可以使内膜不完整、,中膜平滑肌增多、管壁增厚及LD减小的现象得到缓解,其中,以高剂量(200mg/kg)GSP治疗组的作用尤为明显,与卡托普利(30mg/kg)治疗组的作用相当。结论:GSP不仅能显著降低RH大鼠尾动脉收缩压,而且对血管重塑有缓解作用,其机制可能与GSP能降低腹主动脉中ET的含量和ERK1/2的蛋白表达有关。
Objective: To investigate the effect of grape seed procyanidins (GSP) on vascular remodeling in renovascular hypertensive rats. Methods: Two rats and one clip were used to establish RH rat model and a sham operation group was established. Two weeks after operation, 28 rats with a systolic blood pressure above 130 mmHg in the caudal artery were selected and randomly divided into 4 groups: model group with high blood pressure and low dose GSP group (50 mg / kg); high dose GSP Treatment group (200 mg / kg) and captopril positive control treatment group (30 mg / kg). After 6 weeks of treatment, the tail artery systolic pressure was measured in each group, stained with hematoxylin-eosin and the shape of thoracic aorta was observed. The number of smooth muscle layers, the thickness of tunica media and the diameter of lumen were measured LD) and MT / LD and other vascular remodeling morphological parameters. The content of endothelin (ET) in abdominal aorta vascular tissue was measured by ELISA. The expression of ERK1 / 2 protein in abdominal aorta was detected by Western blotting. Results: Compared with the sham operation group, the systolic pressure, MT, MT / LD, ET contents, the number of smooth muscle layers and the expression of ERK1 / 2 in the model group were significantly increased after 6 weeks of treatment. Thoracic aortic intima is not complete, increased in the smooth muscle, wall thickening, and LD decreased. Compared with the model group, GSP low (50mg / kg) and high (200mg / kg) can reduce the tail artery systolic blood pressure, MT and MT / LD, The increase of number and the protein expression of ERK1 / 2 also alleviated the intimal intima, the increase of smooth muscle in medial membrane, the thickening of the wall and the decrease of LD. Among them, high dose (200mg / kg) The effect of the GSP treatment group was particularly pronounced, comparable to that of the captopril (30 mg / kg) treatment group. CONCLUSION: GSP can not only significantly reduce the systolic pressure of the tail artery of RH rats, but also relieve the remodeling of vascular remodeling. The mechanism may be related to the decrease of ET content and ERK1 / 2 protein expression in the abdominal aorta by GSP.