慢性肾脏病高血压大鼠主动脉收缩高反应的机制  

Mechanism of aortic hypercontractile response in chronic kidney disease rats with hypertension

作　　者：胡娟 杨真祯 邝素娟[3] 连智雯 柯贵宝 廖如意 陈雪芹 马建超 黎思嘉 张丽 李卓 冯仲林 梁华般 林婷 董伟 李锐钊 李志莲 章斌 梁馨苓 史伟 邓春玉 刘双信[1,2] HU Juan;YANG Zhenzhen;KUANG Sujuan;LIAN Zhiwen;KE Guibao;LIAO Ruri;CHEN Xueqin;MA Jianchao;Li Sijia;ZHANG Li;LI Zhuo;FENG Zhonglin;LIANG Huaban;LIN Tin;DO NG Wei;El Ruizhao;LI Zhilian;ZHANG Bin;LIANG Xinling;Sill Wei;DENG Chunyu;LIU Shnangxin(The Second School of Clinical Medicine,Southern Medical University,Guangzhou 510080,China;Department of Nephrology,Guangdong General Hospital,Guangdong Academy of Medical Science,Guangzhou 510080,China;Medical Research Center of Guangdong General Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,China)

机构地区：[1]南方医科大学第二临床医学院,广州510080 [2]广东省人民医院(广东省医学科学院)肾内科 [3]广东省人民医院(广东省医学科学院)医学研究中心

出　　处：《肾脏病与透析肾移植杂志》2018年第5期445-450,472,共7页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：国家临床重点专科建设项目;国家自然科学基金项目(81470440;81670665;81870508);广州市科技计划项目(201707010009);广东省人民医院医学科学基金

摘　　要：目的:探讨慢性肾脏病(CKD)继发高血压与主动脉舒缩功能改变之间的关系及其机制。方法:(1)造模:将正常SD大鼠随机分为假手术组(对照组)和CKD组,通过5/6肾切除法制作大鼠CKD模型。术前、术后8周、术后16周分别检测血清肌酐、钙、磷、甲状旁腺素水平,术前及第16周测量大鼠血压。(2)主动脉张力测定:第16周处死大鼠,镜下选取胸主动脉制备血管环,采用累积浓度给药法分别予血管收缩剂与血管舒张剂,通过血管张力测定仪观察血管张力的变化。(3)采用Western Blot检测胸主动脉上相应的受体蛋白表达。结果:(1)第16周时CKD组大鼠血清肌酐、血钙、血磷、甲状旁腺素和尾动脉收缩压及舒张压较对照组均明显升高。(2)CKD大鼠胸主动脉对血栓素A2类似物(U46619)刺激下产生的收缩力明显增强(162. 66±14. 29 vs 121. 39±15. 47,P<0. 01);对60 mmol/L的氯化钾和苯肾上腺素(Phe)诱导的收缩,两组未见明显差异。(3) CKD组大鼠胸主动脉环对内皮依赖性血管舒张剂乙酰胆碱(Ach)和非内皮依赖性血管舒张剂硝普钠(SNP)所触发的舒张反应均低于对照组,Ach(67. 78±6. 18 vs 83. 92±5. 42,P<0. 01),SNP(95. 45±1. 33 vs 98. 90±0. 60,P<0. 01)。(4) CKD组大鼠胸主动脉上血栓素A2受体蛋白(TXA2受体)表达较对照组明显增多,肾上腺素受体蛋白及L-型钙通道(Cav1. 2)蛋白表达无差异。结论:CKD组大鼠胸主动脉对TXA_2类似物刺激收缩力增强,其原因可能与血管上TXA2受体蛋白增多有关;同时CKD大鼠胸主动脉的内皮及非内皮依赖性舒张功能均有受损,这些变化可能参与了CKD高血压大鼠主动脉收缩高反应性。Objective： To investigate the relationship and mechanism between the genesis of hypertension in chronic kidney disease（CKD） and the change of aortic systolic and diastolic function. Methodology： （ 1 ） CKD animal model：Female Sprague Dawley rats were divided into control and CKD groups randomly. The CKD model of rats was generated by 5/6 nephrectomy.Serum levels of creatinine, calcium, phosphorus and parathyroid hormone at 0,8 and 16 week after operation were measured respectively, systolic pressure was tested at 0 and 16 week after operation. （2） Aortic tension determination：The rats were killed and the thoracic aortas were dissected.The thoracic aorta were selected to make vascular rings. The tension variations of thoracic aortas induced by vasoconstrictor/vasodilator with cumulative concentration administration method were measured through vascular tension tester. （3） Expression of corresponding receptors on these vessels were checked with western blot. Results ： （ 1 ） The serum of levels creatinine, calcium, phosphorus, parathyroid hormone, systolic and diastolic pressure were significantly elevated in CKD rats at 16 weeks after operation compared with control group. （2） Rats in C KD group showed an increased contraction response （162. 66 ±14.29 vs 121.39 ± 15.47, P〈 0. 01 ） to U46619 （a thromboxane-A2 analogue） compared with that of control group; but the contractility had no difference when response to 60K （ high potassium solution） and Phe （ phenylephrine ）. （ 3 ） Both of the endothelium-dependent relaxation induced by acetylcholine （Ach） （ 67. 78±6. 18 vs 83.92±5.42, P〈O. 01 ）, and the endothehum-independent relaxation induced by sodium nitroprusside （SNP） decreased in CKD groups （95.45± 1.33 vs 98.90±0. 60,P〈0. 01 ）. （4） Compared with control group, the expression of TXA2 receptor on the thoracic aorta was significantly higher in CKD rats; while the expression of al receptor and L-type calcium channel protein had no sign

关 键 词：慢性肾脏病 高血压 血栓素A2 舒张功能 血管张力 

分 类 号：R692[医药卫生—泌尿科学] R544.1[医药卫生—外科学]