平肝潜阳法对高血压模型大鼠下丘脑蛋白质表达的影响

Effect of Therapy of Soothing Liver and Subsiding Yang on Hypothalamic Protein Expression in Hypertensive Rats

【目的】观察平肝潜阳法对高血压肝阳上亢证模型大鼠下丘脑蛋白质表达差异的影响,从蛋白质组学水平探讨其降血压和改善肝阳上亢证症状的分子机制。【方法】选用自发性高血压大鼠(SHR)灌服附子汤法复制高血压肝阳上亢证大鼠模型,以SD大鼠作正常对照,治疗组给予天麻钩藤饮加减方灌胃给药(0.1g/mL);采用二维凝胶电泳(2-DE)分离大鼠下丘脑蛋白质,获得差异表达蛋白质;利用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)和数据库分析鉴定差异表达蛋白质。【结果】高血压肝阳上亢证大鼠模型复制成功,其易激惹程度、饮水量、收缩压等与正常组比较,差异均有显著性意义(P<0.01);治疗组给予中药天麻钩藤饮加减方治疗后,易激惹程度好转,饮水量减少,收缩压下降,与模型组比较差异均有显著性意义(P<0.01)。肝阳上亢模型组蛋白质图谱中有5个蛋白质斑点,与正常组比较表达上升2倍及以上,且同一点在平肝潜阳法治疗组中表达下降2倍及以上;有10个蛋白质斑点表达下降2倍及以上,且同一点在平肝潜阳法治疗组中表达上升2倍及以上。【结论】平肝潜阳法治疗高血压肝阳上亢证的作用可能与下丘脑某些蛋白质的改变有关。

Objective To observe the effect of therapy of soothing liver and subsiding yang on hypothalamic protein expression in hypertensive rats with hyperactivity of liver yang, and to explore its therapeutic molecular mechanism for hypertension. Methods Spontaneous hypertensive rats （SHR） were given gastric gavage of Aconiti Praeparatae Decoction （APD） to induce hypertensive rat model with hyperactivity of liver yang, and SD rats served as the normal control. The treatment group received modified Tianma Gouteng Decoction （TGD, 0.1 g/mL）. Two-dimension gel electrophoresis （2-DE） was used to separate the hypothalamic proteins, and the differential expressed proteins were identified by matrix - associated laser desorption - ionization time - of - flight mass spectrometry （MALDI-TOF-MS） and database analysis. Results Hypertensive rat model with hyperactivity of liver yang was established successfully. The irritation degree, in-take water volume and systolic pressure were increased in the model group （ P 〈 0. 01 compared with the normal group）, and were decreased after treatment with TGD. The expression amount of 5 protein spots in the model group was increased two times as much as or more over in the normal group, and was decreased two times as much as or more over than that in the treatment group. While the expression amount of 10 protein spots in the model group was decreased two times as much as or more over than that in the normal group, and was increased two times as much as or more over in the treatment group. Conclusion The therapeutic mechanisms of therapy of soothing liver and subsiding yang for hypertension with hyperactivity of liver yang may be related with the changes of some hypothalamic proteins.