川穹嗪对肾性高血压大鼠左心室肥厚和还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶的影响  

Effects of tetramethylprazine on left ventricular hypertrophy and nicotinamide-adenine dinucleotide oxidases in renovascular hypertension of rats

作　　者：吕行直 李瑞芳[1] 罗雪婷[1] 汪玲[1] 王红伟[2] 王宏运[3] 

机构地区：[1]河南科技大学医学院药理学与分子生物学重点实验室,河南洛阳471023 [2]河南科技大学护理学院,河南洛阳471023 [3]河南科技大学第一附属医院心血管内科,河南洛阳471003

出　　处：《中国临床药理学杂志》2017年第6期513-517,共5页The Chinese Journal of Clinical Pharmacology

基　　金：洛阳市科技发展计划基金资助项目(1401085A-1)

摘　　要：目的研究川穹嗪(TMP)对肾性高血压大鼠的左心室肥厚及还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶的作用。方法用双肾双夹法建立肾性高血压大鼠模型,按照体重将大鼠随机分为5组:假手术组、模型组、低高2个剂量实验组(TMP,30,60 mg·kg^(-1)·d^(-1))、对照组(坎地沙坦,10 mg·kg^(-1)·d^(-1)),连续给药2周。颈动脉插管,检测血流动力学参数;试剂盒检测血清氧化应激指标;称取左心室重量,计算左心室体重指数(LVW/BW);以HE染色观察左心室组织的形态学改变;用逆转录聚合酶链反应和蛋白免疫印迹法检测左心室脑钠肽(BNP)、β-肌球蛋白重链(β-MHC)和还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶的蛋白水平。结果治疗后低、高2个剂量实验组大鼠的主动脉收缩压和舒张压(AoSP,AoDP)、左心室收缩末压和舒张末压(LVESP,LVEDP)均显著降低,而室内压最大的上升速率(+dp/dt_(max))和下降速率(-dp/dt_(max))均显著升,高差异均有统计学意义(P<0.05)。给药后,与模型组的LVW/BW为(2.8±0.3)mg·g^(-1)比较,低、高2个剂量实验组和模型组分别为(1.9±0.2),(1.7±0.4)mg·g^(-1),差异有统计学意义(P<0.05)。与模型组比较低、高2个剂量实验组的SOD显著升高而MDA和H_2O_2显著下降,差异均有统计学意义(均P<0.05)。给药后,低、高2个剂量实验组和模型组的左心室Nox2的蛋白表达分别为0.82±0.08,0.57±0.05,1.30±0.13,这3组的Nox4的蛋白表达分别为1.00±0.10,0.79±0.07,1.32±0.15,这3组的P47phox的蛋白表达分别为0.88±0.08,0.65±0.06,1.23±0.15,均较模型组显著降低,差异均有统计学意义(均P<0.05)。结论 TMP可以改善肾性高血压大鼠的左心室肥厚,其机制可能与降低高血压大鼠左心室的NADPH(Nox2、Nox4及P47phox)蛋白表达、改善氧化应激有关。Objective To investigate the effects of tetramethylprazine（TMP） on left ventricular hypertrophy and the regulation of nicotinamide-adenine dinucleotide（NADPH） oxidases in renovascular hypertension of rat.Methods Hypertensive rats were obtained by using two-kidney-two-clip（2K2C） method.Rats were classified into sham-operated group,model group,low,high dose experimental groups（TMP,30,60 mg · kg^-1 · d^-1） and control group（candesartan,10 mg · kg^-1 · d^-1）.The drugs were continuously administered for 2 weeks.Left ventricular（LV） hemodynamic parameters,serum superoxide ismutase（SOD）,dmalondialdehyde（MDA） and hydrogen peroxide（H2O2） levels were measured.The ratio of LV weight to body weight（LVW/BW） was calculated.Hematoxylin-eosin（HE） staining was used for morphological analysis.RT-polymerase chain reaction and Western-blot were performed to investigate the protein expressions of brain natriuretic peptide（BNP）,β-myosin heavy chain（β-MHC） and NADPH oxidases（Nox2,Nox4 and P47phox）.Results Compared with model group,aortic systolic pressure（AoSP）,aortic diastolic pressure（AoDP）,LV end-systolic pressure（LVESP）,LV end-diastolic pressure（LVEDP） significantly decreased in low,high dose experimental groups with siginificanly（all P〈0.05） while（±dp/dtmax） and（-dp/dtmax） increased in low,high dose experimental groups with siginificanly（P〈0.05）.Compared with model group on LVW/BW（2.8±0.3） mg · g^-1,LVW/BW of（1.9±0.2）,（1.7±0.4） mg·g^-1 in low,high dose experimental groups significantly decreased（P〈0.05）.Compared with model group SOD significantly increased while MDA and H2O2 decreased in low,high dose experimental groups with significantly（all P〈0.05）.The protein expressions of Nox2 in low,high experimental groups and model group were 0.82 ± 0.08,0.57 ± 0.05,0.30 ± 0.13;the protein expressions of Nox4 in above three groups were1.00 ±0.10,0.79 ± 0.07,1.32 ± 0.15 and the protein expressions of P47 pho

关 键 词：川穹嗪 肾性高血压 左心室肥厚 氧化应激 还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶 

分 类 号：R28[医药卫生—中药学]