柚皮素通过激活大电导钙激活钾离子电流对大鼠肠系膜动脉的松弛作用

Relaxant effect of naringenin on the mesenteric artery by activating the large-conductance Ca^(2+)-activated K^+ channel currents in rats

目的研究柚皮素对大鼠离体肠系膜动脉的松弛作用,并探讨与大电导钙激活钾离子通道(BK_(Ca))的相关性。方法从SD大鼠分离得到肠系膜动脉,并分离其血管平滑肌细胞(VSMCs)。(1)将肠系膜动脉分为2组(及其进行张力测定):正常对照组(先用血管加压素或者KCl收缩血管,然后加入不同浓度的等量溶剂);实验组(先用血管加压素或者KCl收缩血管,然后加入不同浓度柚皮素,进行舒张)。将肠系膜动脉先用血管加压素或KCl收缩,记录其张力;然后在1×10^(-5)mol·L^(-1)柚皮素存在的情况下,再次加入血管加压素或KCl收缩,比较其张力变化。(2)正常对照组(提前孵育等量溶剂,然后加入血管加压素或者KCl收缩血管);实验组(提前孵育柚皮素,然后加入血管加压素或者KCl收缩血管)。(3)将肠系膜VSMCs分为2组观察记录其BK_(Ca)电流:正常对照组(先记录基础BK_(Ca)电流,然后加入溶剂后再次记录);实验组(先记录基础BK_(Ca)电流,然后加入1×10^(-5)mol·L^(-1)柚皮素后再次记录)。在记录基础BK_(Ca)电流之后,正常对照组加入溶剂,实验组加入1×10^(-5)mol·L^(-1)柚皮素。观察柚皮素对肠系膜动脉VSMCs BK_(Ca)电流的影响。结果 (1)用血管加压素收缩后,正常对照组和实验组的最大舒张百分比分别是(99. 08±4. 23)%和(38. 34±2. 57)%;用KCl收缩后,这2组的最大舒张百分比分别是(98. 93±3. 09)%和(35. 46±4. 05)%,组间比较差异均有统计学意义(均P <0. 01)。(2)孵育柚皮素前后,这2组的肠系膜动脉对血管加压素的收缩幅度分别为(3. 09±0. 27),(1. 75±0. 18) mN;这2组对KCl的收缩幅度分别为(3. 48±0. 31),(1. 48±0. 16) mN,组间比较差异均有统计学意义(均P <0. 01)。(3)这2组的大鼠肠系膜动脉VSMCs的BK_(Ca)电流最大电流密度分别为(25. 36±4. 12),(42. 58±3. 27) pA/pF,组间比较差异有统计学意义(P <0. 01)。结论柚皮素可以松弛大鼠肠系膜动脉,其松弛作用与增加BK_(Ca)电流有关。

Objective To study the relaxant effect of naringenin on isolated mesenteric artery in rats and to explore the relationship to large-conductance Ca2 +-activated K+channel( BKCa) currents. Methods Mesenteric artery and its vascular smooth muscle cells( VSMCs) were obtained from rat mesentery.( 1) Mesenteric arteries were divided into two groups: normal control group( the arteries were first contracted by vasopressin or KCl and then solvent was added);experimental group( the arteries were first contracted by vasopressin or KCl and then different concentrations of naringenin were added).( 2) The mesenteric artery wascontracted by vasopressin or KCl to record its tension,and then vasopressin or KCl was added to the mesenteric artery again in the presence of solvent or 1 ×10-5 mol·L-1 naringenin.( 3) The VSMCs were divided into two groups and their BKCacurrents were recorded: normal control group( first recording basic BKCacurrent,then solvent was added);experimental group( first recording basic BKCacurrent,then 1 ×10-5 mol·L-1 naringenin was added). Results( 1)The mesenteric artery was pre-contracted by vasopressin,the maximal relaxation percentages of the normal control group and the experimental group were( 99. 08 ± 4. 23) % and( 38. 34 ± 2. 57) %,respectively;the mesenteric artery was pre-contracted by KCl,the maximal relaxation percentages of the two groups were( 98. 93 ± 3. 09) % and( 35. 46 ± 4. 05) %,respectively. Comparison between normal control group and experimental group,the difference of the factors were significant( all P < 0. 01).( 2) Before and after incubation of naringenin,the contraction amplitude of mesenteric artery to vasopressin in the 2 groups were( 3. 09 ± 0. 27),( 1. 75 ± 0. 18) mN,respectively;the contraction amplitude of mesenteric artery to KCl in the 2 groups were( 3. 48 ± 0. 31),( 1. 48 ± 0. 16) mN,respectively. Comparison between normal control group and experimental group, the difference of the factors were significant( all P < 0. 01).( 3) The maximum current densities of BKCacurrents in VSMCs of mesenteric artery in the 2 groups were( 42. 58 ± 3. 27),( 25. 36 ± 4. 12) pA/pF,respectively. Comparison between normal control group and experimental group,the difference was significant( P < 0. 01). Conclusion Naringenin could relax the mesenteric artery in rats,and its relaxation is related to the increase of BKCacurrents.