一氧化氮通路可能部分介导salusin-β中枢降血压作用

Central Hypotensive Effect of Salusin-β is Partly Mediated by Nitric Oxide

背景 Salusins系2003年新发现的广泛存在于造血系统、内分泌系统和中枢神经系统内具有降低血压和丝裂原样效应的生物活性肽。成熟的salusins包括salusin-α和salusin-β两个单体。尽管salusins广泛分布于人和大鼠中枢神经系统内,但salusin-β的中枢心血管效应及其机制尚未得到充分研究。目的通过侧脑室给药的方法探讨salusin-β的中枢心血管效应及其机制。方法雄性SD大鼠57只,腹腔注射氨基甲酸乙酯1.0g/kg麻醉,人工通气,股动脉、静脉插管,固定于立体定位仪。其中25只大鼠随机分为对照组[侧脑室注射人工脑脊液(aCSF),n=4]、salusin-β100pmol组(n=7)、200pmol组(n=7)、400pmol组(n=7)。给药后观察大鼠血压和心率。其余32只大鼠为预先给予阻断剂组。随机分为aCSF+salusin-β组(n=4)、N甲基D天门冬氨酸(NMDA)受体拮抗剂MK-801+salusin-β组(n=7)、内皮源性一氧化氮合酶(eNOS)抑制剂NG硝基L精氨酸甲酯(L-NAME)+salusin-β组(n=7)、γ氨基丁酸(GABA)受体阻断剂荷包牡丹碱(Bic)+salusin-β组(n=7)、salusin-α+salusin-β组(n=7)。先分别侧脑室注射MK-801等阻断剂,10min后待血压平稳再分别侧脑室注射salusin-β,观察给药后大鼠血压和心率的变化。结果侧脑室注射salusin-β100pmol[给药前(99±16)比给药后(85±16)mmHg,P<0.05]、200pmol[给药前(97±8)比给药后(82±9)mmHg,P<0.05]或400pmol[给药前(86±21)比给药后(73±29)mmHg,P<0.05],各剂量salusin-β均降低麻醉大鼠血压,但对心率无影响。侧脑室注射等量的aCSF对麻醉大鼠的心血管活动不产生显著作用。预先给予eNOS抑制剂L-NAME(1.15μmol)能有效减弱侧脑室注射salusin-β的降压作用[L-NAME+salusin-β组(-6±10)比aCSF+salusin-β组(-17±16)mmHg,P<0.05],侧脑室预先注射MK-801(0.5μmol)、Bic(0.3nmol)或salusin-α(200pmol)均不影响侧脑室注射salusin-β产生的降血压效应。结论侧脑室注射salusin-β显著降低麻醉大鼠的血压,侧脑室注射salusin-β的降压作用可能部分由一氧化氮通路介导。

Background Salusin-α and salusin-β,two newly identified bioactive peptides exsiting widely in hematopoietic system,endocrine system and central nervous system（CNS）,consist of 28 and 20 amino acid residues,respectively,exsiting widely in hematopoietic system,endocrine system and CNS.Salusins have been shown to exert a variety of functions in the cardiovascular,endocrine and immune systems.Intravenous administration of salusins to rats tends to caused hypotension and bradycardia.Although it has been proved that salusin-β distributes widely in CNS,the cardiovascular function of central salusin-β is unclear.Objective To study the central cardiovascular effects of salusin-β by injection of salusin-β into lateral cerebral ventricle（LCV）in anesthetized rats and its mechanism.Methods Fifty seven anesthetized,paralyzed male SD rats were employed in the present study.Twenty-five of them were randomized into control group（aCSF,n=4）,salusin-β 100 pmol group（n=7）,salusin-β 200 pmol group（n=7）,and salusin-β 400 pmol group（n=7）.Salusin-β（100,200 or 400 pmol）or aCSF was injected into LCV to observe the central cardiovascular effects of central salusin-β.In another 32 rats,MK-801（n=7）,L-NAME（n=7）,Bic（n=7）,salusin-α（n=7）or aCSF（n=4）was applied into LCV of rats 10 min before salusin-β（200 pmol）was injected.Results LCV injection of salusin-β produced a significant decrease in BP [（99±16）vs（85±16）mm Hg in salusin-β 100 pmol group,P0.05;（97±8）vs（82±9）mm Hg in salusin-β 200 pmol group,P0.05;（86±21）vs（73±29）mm Hg in salusin-β 400 pmol group,P0.05],with little effect on HR.LCV injection of aCSF didn＇t alter BP or HR in anesthetized rats.The hypotensive effect induced by LCV injection of salusin-β was significantly blocked by the pretreatment with central application of endothelial NOS inhibitor L-NAME [（-6±10）mm Hg in L-NAME＋salusin-β group vs（-17±16）mm Hg in aCSF＋salusin-β group,P0.05],with little effect by MK-801,Bic or salusin-α administration.Conclusion Our present study shows that LCV injection of salusin-β produces hypotension in rats,which is partly mediated by nitric oxide（NO）.