Zhao Hai-Ping, Hong Ying, Xie Jun-Da, Xie Xin-Ran, Wang Jing, Fan Jiang-Bo
College of Traditional Chinese Pharmacy, Beijing University of Traditional Chinese Medicine, Beijing 100102, China.
Yao Xue Xue Bao. 2007 Mar;42(3):336-41.
The purpose of this study is to evaluate the effects and the underline mechanisms of berberine on the cardiac function and left ventricular remodeling in rats with renovascular hypertension. The renovascular hypertensive model was established by the two-kidney, two-clip (2K2C) method in Sprague-Dawley (SD) rats. Two weeks after surgery, all the operated SD rats were randomly assigned into four groups: (1) renovascular hypertensive model group; (2) berberine 5 mg x kg(-1) group; (3) berberine 10 mg x kg(-1) group; (4) captopril 45 mg x kg(-1) group; and the sham operated rats were used as control. Four weeks after the drugs were administered, the cardiac function was assessed. The ratios of heart weight to body weight (HW/BW), left ventricular weight to body weight (LVW/BW) and right ventricular weight to body weight (RVW/BW) were compared between groups. Coronal sections of the left ventricular tissue (LV) were prepared for paraffin sections, picrosirius red and HE staining was performed. The left ventricular wall thickness (LVWT), interventricular septal thickness (IVST), the parameters of myocardial fibrosis indicated by interstitial collagen volume fraction (ICVF) and perivascular collagen area (PVCA) were assessed. Nitric oxide (NO), adenosine cyclophosphate (cAMP) and guanosine cyclophosphate (cGMP) concentrations of left ventricular tissue were measured. Berberine 5 mg x kg(-1) and 10 mg x kg(-1) increased the left ventricular +/- dp/dt(max) and HR. Berberine 10 mg x kg(-1) decreased HW/BW and LVW/BW. The image analysis showed that both 5 and 10 mg x kg(-1) of berberine decreased LVWT, ICVF and PVCA, while increased the NO and cAMP contents in left ventricular tissue. Berberine could improve cardiac contractility of 2K2C model rats, and inhibit left ventricular remodeling especially myocardial fibrosis in renovascular hypertension rats. And such effects may partially associate with the increased NO and cAMP content in left ventricular tissue.
本研究旨在评估黄连素对肾血管性高血压大鼠心功能及左心室重构的影响及其潜在机制。采用双肾双夹（2K2C）法在Sprague-Dawley（SD）大鼠中建立肾血管性高血压模型。术后两周，将所有接受手术的SD大鼠随机分为四组：（1）肾血管性高血压模型组；（2）黄连素5 mg·kg⁻¹组；（3）黄连素10 mg·kg⁻¹组；（4）卡托普利45 mg·kg⁻¹组；假手术大鼠作为对照组。给药四周后，评估心功能。比较各组心脏重量与体重比值（HW/BW）、左心室重量与体重比值（LVW/BW）和右心室重量与体重比值（RVW/BW）。制备左心室组织（LV）的冠状切片用于石蜡切片，进行天狼星红和苏木精-伊红染色。评估左心室壁厚度（LVWT）、室间隔厚度（IVST）、由间质胶原容积分数（ICVF）和血管周围胶原面积（PVCA）表示的心肌纤维化参数。测量左心室组织中一氧化氮（NO）、环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）的浓度。黄连素5 mg·kg⁻¹和10 mg·kg⁻¹可增加左心室±dp/dt（max）和心率。黄连素10 mg·kg⁻¹可降低HW/BW和LVW/BW。图像分析显示，5 mg·kg⁻¹和10 mg·kg⁻¹的黄连素均可降低LVWT、ICVF和PVCA，同时增加左心室组织中NO和cAMP的含量。黄连素可改善2K2C模型大鼠的心脏收缩力，并抑制肾血管性高血压大鼠的左心室重构，尤其是心肌纤维化。且这种作用可能部分与左心室组织中NO和cAMP含量增加有关。
