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目的:研究葡萄籽原花青素对自发性高血压大鼠(SHR)肾损伤的保护作用并对其机制进行探讨。方法:8周龄雄性自发性高血压大鼠24只随机分成4组,每组6只:模型组、葡萄籽原花青素50mg/kg剂量组和200mg/kg剂量组、卡托普利组(30mg/kg),6只8周龄雄性Wistar-Kyoto大鼠设为对照组。治疗6周后,测定大鼠尾动脉收缩压(SBP);ELISA法测定大鼠尿中视黄醛结合蛋白(RBP)和α1微球蛋白(α1-MG)含量;HE染色下用图像分析软件测定肾内小动脉中膜厚度与血管内径比值(MT/LD);Masson染色下观察肾脏纤维化情况,测量并计算肾小球胶原纤维沉积评分(GCDS)及肾小管间质病变评分(TIDS);Western blot法检测肾皮质中磷酸化细胞外信号调节激酶1/2(p-ERK1/2)蛋白表达情况。结果:葡萄籽原花青素50mg/kg和200mg/kg剂量组能显著降低自发性高血压大鼠尾动脉收缩压、尿液中RBP和α1-MG含量、肾内小动脉MT/LD,减少肾脏组织中胶原纤维含量、降低GCDS和TIDS以及肾皮质中p-ERK1/2蛋白表达,葡萄籽原花青素200mg/kg剂量组的作用尤为显著。结论:葡萄籽原花青素对自发性高血压大鼠肾脏损伤有减轻作用,其机制可能与葡萄籽原花青素降低尾动脉收缩压、减少肾皮质中p-ERK1/2蛋白表达有关。
Objective: To study the protective effect of grape seed proanthocyanidins on renal injury in spontaneously hypertensive rats (SHR) and its mechanism. Methods: Twenty-four male 8-week-old spontaneously hypertensive rats were randomly divided into 4 groups with 6 mice in each group: model group, grape seed proanthocyanidin 50mg / kg dose group and 200mg / kg dose group, captopril group (30mg / kg), and 6 Wistar-Kyoto rats of 8 weeks old were set as the control group. After 6 weeks of treatment, the rat tail artery systolic pressure (SBP) was measured; the contents of retinaldehyde retinol binding protein (RBP) and α1 microglobulin (α1-MG) in rat urine were measured by ELISA; (MT / LD). The renal fibrosis was observed under Masson staining. The glomerular collagen deposition (GCDS) and tubulointerstitial lesions (TIDS) were measured and calculated. The protein expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1 / 2) in renal cortex was detected by Western blot. Results: Grape seed proanthocyanidins 50mg / kg and 200mg / kg dose group can significantly reduce spontaneous hypertensive rats tail artery systolic blood pressure, urinary RBP and α1-MG content, renal arterioles MT / LD, reduce renal tissue The content of collagen fibers, the expression of p-ERK1 / 2 protein in GCDS and TIDS and renal cortex were decreased, and the effect of grape seed proanthocyanidin 200 mg / kg was especially significant. CONCLUSION: Grape seed proanthocyanidins have a protective effect on renal injury in spontaneously hypertensive rats. The mechanism may be related to the fact that grape seed procyanidins reduce the contractile pressure of caudal artery and reduce the expression of p-ERK1 / 2 in renal cortex.