兔肾脏二甲基精氨酸二甲基氨基水解酶活性在动脉粥样硬化和虎杖干预中的变化

Change of dimethylarginine dimethylaminohydrolase activity in hypercholesterolemic rabbits and interventional effects of Polygonum cuspidatum Sieb. et Zucc

目的:研究动脉粥样硬化(AS)时二甲基精氨酸二甲基氨基水解酶(DDAH)活性的改变以及虎杖(HZ)对其的干预作用。方法:将36只日本大耳白兔分为正常对照组(NC组)、高脂组(HC组)、高脂加 1、3、9 g/d 3种不同剂量HZ组(SHZ组、MHZ组、LHZ组)和高脂加L 精氨酸组(L Arg组),测定非对称性二甲基精氨酸(ADMA) 水平及肾脏DDAH活性。结果: HC组AS斑块明显,腹主动脉壁中层细胞一氧化氮合酶(NOS)活性增强,内皮细胞染色减弱,ADMA水平增高,而肾脏DDAH活性却明显降低;不同剂量 HZ组呈剂量依赖性改善上述各项指标。结论:AS时DDAH活性降低而致血浆ADMA水平增高和 NOS系统紊乱,HZ能呈剂量依赖性地提高DDAH活性并具有抗AS效应。

Objective:To study the change of the activity of dimethylarginine dimethylaminohydrolase(DDAH) in atherosclerosis(AS) and the interventional effects of Polygonum cuspidatum sieb. et Zucc. Method:Thirty-six Japanese rabbits were randomized into 6 groups. Except the control group(NC group),all the rest 5 groups were given atherogenic diet. Among those five groups,four were feeding with polygonum cuspidatum sieb. et Zucc. 1 g/d (SHZ group),3 g/d (MHZ group),9 g/d (LHZ group) or L-arginine 4.22 g/d (L-Arg group) separately. The following contents were surveyed: the area of AS plaque in thoracic aorta(dyeing with Sudan Ⅳ), plasma ADMA( aminoacid analyzer), NOS activity on the wall of the abdominal artery (dyeing with NBT) and the activities of DDAH in kidney (according to the method established by our laboratory). Result:In HC group,AS pla que in thoracic aorta was serious,dyeing of NOS on the medial layer of the artery wall was much darker,and that on the endothelium was on the contrary. Plasma ADMA was elevated significantly. And a significant decrease in the activity of DDAH was observed in HC group. Polygonum cuspidatum sieb. et Zucc. could ameliorate the above parameters (including the activity of DDAH in kidney) in a dose-dependant manner. The sequence of the beneficial result was as follows: SHZ group < MHZ group < LHZ group. The resistant effect of LHZ group is almost the same as that of L-Arg group. Although there was fewer area of AS plaque in L-Arg group, there was no signifi- cant difference in the rest parameters between L-Arg group and HC group. Conclusion:In AS rabbit, the decrease of the activity of DDAH caused the elevated plasma ADMA and the disorder of NOS system. Polygonum cuspidatum sieb. et Zucc. could elevate the decreased activity of DDAH caused by atherogenic diet in a dose-dependant manner, and therefore resist AS.