犬尿氨酸氨基转移酶和犬尿喹啉酸在自发性高血压大鼠中的变化  

Kynurenine Aminotransferase and Kynurenic Acid in Spontaneous Hypertensive Rats

作　　者：李宁宁[1] 肖冰[1] 张怡[1] 朱鼎良[1] 高平进[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院·上海市高血压研究所,上海市血管生物学重点实验室,上海200025

出　　处：《中华高血压杂志》2008年第7期625-628,共4页Chinese Journal of Hypertension

基　　金：国家重点基础研究发展计划“973”(2004CB518603,2006CB503804)资助课题;国家自然科学基金(30600243)资助课题;上海自然科学基金(06ZRl4066)资助课题

摘　　要：目的犬尿氨酸氨基转移酶(KAT)催化犬尿氨酸(KYN)生成犬尿喹啉酸(KYNA)。研究表明中枢KAT 及 KYNA 可能参与血压调节,但外周 KAT 变化及 KYNA 生成与血压的关系尚无报道。检测肾脏 KATⅡ基因表达,KAT 活性,及尿 KYNA 含量在自发性高血压大鼠(SHR)和 WKY 大鼠(正常对照组)的变化。方法采用实时定量 PCR 技术检测 KATⅡ基因表达,高效液相色谱(HPLC)检测尿 KYNA 及 KAT 活性(通过测定其酶促反应产物 KYNA)。结果虽然肾皮质和肾髓质 KATⅡ基因 mRNA 表达在 SHR 与 WKY 之间差异无统计学意义(P>0.05);但 SHR 肾皮质 KAT 的活性显著低于 WKY[(0.563±0.037)vs(1.037±0.131)μmol/(g·min),P=0.017]。同时发现 SHR 组尿 KYNA 含量在显著低于 WKY 组[(7.8±1.8)vs(19.9±3.5)μmol/24 h,P=0.013]。相关分析显示,肾皮质 KAT 的活性(r=-0.418,P=0.023)和尿 KYNA 含量(r=-0.723,P=0.001)与血压都呈显著负相关。结论 SHR 大鼠肾皮质 KAT 活性降低及尿 KYNA 含量减少,提示除中枢 KAT 及 KYNA变化外,肾皮质 KAT 活性变化导致的 KYNA 改变亦可能影响血压。Objective Kynurenine aminotransferase （KAT） catalyzed kynurenine （KYN） to Kynurenic acid （KYNA）. Evidence suggested that endogenous KYNA and KAT in the brain might play a role in the blood pres- sure central regulation. This study was to analyze the alteration of KYNA content, as well as the enzyme activity and gene expression of KAT in kidney in spontaneous hypertensive rat （SHR） compared with Wistar-Kyoto rats （WKY）. Methods 16-week-old male SHR and WKY were used for this study. The mRNA expression of KAT Ⅱ was detected by real-time polymerase chain reaction （RT-PCR）. The activity of KAT was assayed by the conversion of L-KYN to KYNA and quantitated by HPLC with fluorescence detection. Urinary KYNA concentration was measured by high performance liquid chromatography （HPLC）. Results The KAT activity in renal cortex was lower in SHR than WKY [0. 563±0. 037 vs 1. 037±0. 131μmol/（g · min）, P=0. 017], although no significant difference was been found in renal cortex and medulla KAT Ⅱ mRNA expression between SHR and WKY（P〉 0.05 ）. The concentration of urinary KYNA, metabolite of the KYN, was significantly lower in SHRs compared to WKYs （7.8±1.8 vs 19.9±3.5 μmol/24 h P=0. 013）. Both KAT activity in renal cortex and KYNA content in urine were negatively correlated to blood pressure（r=-0. 418, P=0. 023; r= -0. 723, P=0. 001）. Conclusion The declined activity of KAT in renal cortex and the deficiency of KYNA concentration in urinary may affect blood pressure regulation in SHR by renal metabolite of the KYN.

关 键 词：自发性高血压大鼠 犬尿喹啉酸 犬尿酸 犬尿氨酸氨基转移酶 

分 类 号：R544.1[医药卫生—心血管疾病] R741.02[医药卫生—内科学]