ATP敏感性钾通道亚基突变对血管生理特性的影响  

Effects of ATP-sensitive Potassium Channel Mutation(Kir6.1[V65M])on Vascular Physiology

作　　者：宋涛[1] 黄燕[1] SONG Tao;HUANG Yan(Department of Cardiology,Renmin Hospital of Wuhan University,Cardiovascular Research Institute,Wuhan University,Hubei Key Laboratory of Cardiology,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院心内科,武汉大学心血管病研究所,心血管病湖北省重点实验室,武汉430060

出　　处：《微循环学杂志》2023年第4期1-5,12,共6页Chinese Journal of Microcirculation

基　　金：国家自然科学基金青年基金项目(82100331);武汉市科技局知识创新专项项目-曙光计划(2022020801020484);中央高校自主科研项目(2042019kf0058)。

摘　　要：目的:探究ATP敏感性钾通道亚基突变(Kir6.1[V65M])对血管生理特性的影响。方法:以同窝野生型(WT,野生组,n=35)及杂合突变小鼠(V65M+/-,突变组,n=52)为研究对象,采用颈动脉插管测定两组小鼠的收缩压和舒张压;分离降主动脉,制成3-5mm左右动脉环,经生物信号采集与分析系统测定动脉环张力的变化;分离单个血管平滑肌细胞,利用全细胞膜片钳技术记录L型钙通道电流;眼眶内眦静脉采血,采用ELISA试剂盒检测血清肾素、血管紧张素、醛固酮表达水平。结果:与野生组小鼠相比,突变组小鼠收缩压和舒张压明显下降(P<0.01)。突变组小鼠在60mmol/L KCl及1μmol/L去甲肾上腺素刺激下的张力改变明显高于野生组小鼠(P<0.05);突变组小鼠动脉环对低浓度(0.1μmol/L)及高浓度吡那地尔(0.3μmol/L)的舒张反应性均大于野生组小鼠(P<0.01)。突变组小鼠血管平滑肌细胞钙电流峰值增加(P<0.05)。与野生组小鼠相比,突变组小鼠肾素、血管紧张素II水平升高(P<0.05)。结论:Kir6.1[V65M]突变使血压下降,反射性引起机体代偿调节,激活RAAS系统,血管平滑肌细胞钙电流增加,使得血管对收缩剂及舒张剂的张力反应性增加。Objective:To explore the effects of ATP-sensitive potassium channel mutation(Kir6.1[V65M])on vascular physiology.Method:Litter wild type(WT,WT group,n=35)and heterozygous mutant mice(V65M+/-,mutant group,n=52)were studied.The systolic blood pressure and diastolic blood pressure were measured by carotid cannula.The descending aorta was dissected and cut into arterial ring around 3-5mm.Then the changes of arterial ring tension were measured by biological signal acquisition and analysis system.The single smooth muscle cell was isolated and the L-type calcium current was recorded by the whole-cell patch clamp.And the blood was collected and the expression level of RAAS system was measured by Elisa kits.Results:Compared with the mice in WT group,the systolic blood pressure and diastolic blood pressure in mutant group mice were much lower(P<0.01).For the arterial contractility test,the arterial tension change of mutant mice in 60mmol/L KCL and 1μmol/L norepinephrine was significantly bigger than that in WT group mice(P<0.05).Besides,the relax reactivity of arterial ring in mutant group mice to low concentration(0.1μmol/L)as well as high concentration(0.3μmol/L)of pinacidil was greater than that of WT group mice(P<0.01).In addition,the peak L type calcium current of smooth muscle cells in mutant group mice was higher than that in WT mice(P<0.05).Meanwhile,compared with the WT mice,the levels of renin and angiotensin II were increased in mutant group mice(P<0.05).Conclusion:Kir6.1[V65M]mutation leads to lower blood pressure,which activates reflexes compensatory regulation of the body,resulting higher RAAS system activity,and can further increase the calcium current of vascular smooth muscle cells and the tension reactivity of blood vessels to constrictors and relaxants.

关 键 词：ATP敏感性钾通道 Kir6.1[V65M]突变 Cantu综合征 血压 血管张力 RAAS系统 

分 类 号：R543.5[医药卫生—心血管疾病]