高盐饮食诱导和两肾一夹法复制高血压大鼠模型的比较

Comparison of the hypertensive rat models induced by high salt diet and two-kidney one-clip method

目的:通过高盐饮食诱导和两肾一夹法分别复制高血压大鼠模型,初步探讨其可能机制。方法:18只雄性SD大鼠随机分成3组(n=6),正常对照组(NC组)、两肾一夹高血压模型组(2K1C组)和高盐饮食性高血压模型组(SH组),采用左肾动脉结扎的方法复制肾性高血压模型,给予含4%Na Cl饲料喂养复制高盐饮食性高血压模型,普通饲料喂养不进行手术措施的为正常对照组。各组大鼠在每天相同时间点测量体质量和血压,连续4周;造模成功后,通过生物信号处理系统测定各组大鼠胸主动脉环张力,HE染色观察各组大鼠肾脏及血管形态学变化,检测血管匀浆中诱导型一氧化氮合酶(i NOS)活性及一氧化氮(NO)含量。结果:同NC组大鼠相比,SH组和2K1C组大鼠血压明显升高(P<0.05),体质量变化无统计学意义;SH组和2K1C组胸主动脉环对去氧肾上腺素(Phe)的收缩反应明显增强(P<0.05),对乙酰胆碱(ACh)的舒张反应显著降低(P<0.05或P<0.01);对硝普钠(SNP)的舒张反应无统计学意义;HE染色显示,SH组和2K1C组肾小体萎缩,肾脏组织结构中的小动脉出现玻璃样变性,主动脉内膜损伤,中膜层增厚且细胞形态改变;SH组和2K1C组血管环匀浆中i NOS活性明显增强(P<0.01),NO含量明显下降(P<0.05)。结论:高盐饮食诱导和两肾一夹法均成功复制高血压大鼠模型,内皮损伤可能是其产生机制之一,前者简易安全,大鼠死亡率低,更接近于临床,是复制高血压大鼠模型的优先选择。

Objective： To compare the hypertensive rat models induced by either high salt diet or two-kidney one-clip（ 2K1C） technique,and preminarily investigate the posssible mechanisms in duplicating such animal models.Methods： Eighteen male SD rats were randomized into normal control group（ NC group）,2K1 C group and high salt diet induced group（ SH group）（ n = 6 for each group）. Duplicating of the hypertensive rat models was performed by2K1 C technique for 2K1 C group,feeding with 4%Na Cl for SH group,and conventional feeding for NC group.The body weight and blood pressure were daily measured in the same time point for the three groups for consecutive 4 weeks. After successful modeling,biological signal processing system was used to measure the tension of aortic annuli,and HE staining was performed to examine the morphological changes of kidney and aortic rings in rats in the three groups.Besides,inducible nitric oxide synthase（ i NOS） activity and nitric oxide（ NO） content in aortic annulus homogenates were determined. Results：Compared to NC group,the systolic blood pressure of SH group and 2K1 C group were significantly increased（ P〈0.05）,yet the body weight showed no significant difference（ P〉0.05）.The tension rate of SH group and 2K1 C group was much more increased with phenylephrine（ Phe） intervention（ P 〈0.05）,yet decreased with acetylcholine（ ACh）（ P〈0.05 or P〈0.01）,and sodium nitroprusside（ SNP） treatment caused no significant variation（ P0.05）.HE staining indicated atrophied renal corpuscle,hyaline degeneration in the small arteries of renal tissue structure,damaged aortic intima and thickened middle membrane layer with cellular derangement as well as significantly increased i NOS activity of aortic annulus homogenates in rats of SH group and 2K1 C group（ P〈0.01）,yet NO content were significantly decreased（ P〈0.05）.Conclusion： Both high salt diet and 2K1 C may be used for duplicating the hypertensive rat models.Successful establishment of such rat models may be associated with endothelial damage.However,high salt diet induction can be prioritized,for such technique appears simpler and safer in performance,with lower death rate.Importantly,such model may be clinical analogue of human hypertension.