salusin-α的中枢降血压机制研究

The Mechanisms of Hypotension Induced by Central salusin-α

目的通过侧脑室给药的方法探讨salusin-α的中枢心血管效应及其机制。方法雄性SD大鼠50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(artificial cerebrospinal fluid,aCSF),n=4],salusin-α100pmol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25只大鼠为预先给予阻断剂组,随机分为对照组aCSF+salusin-α组(n=4)、N-甲基-D-天门冬氨酸(NMDA)受体拮抗剂MK-801+salusin-α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-α组(n=7)、γ-氨基丁酸(GABA)受体阻断剂荷包牡丹碱(Bic)+salusin-α组(n=7)。先分别侧脑室给药MK-801等阻断剂,10min后待血压平稳再分别侧脑室注射salusin-α,观察给药后大鼠血压和心率的变化。结果侧脑室注射salusin-α100pmol(给药前:99±11mmHg比给药后:83±13mmHg,P<0.05)200pmol(给药前:99±17mmHg比给药后:87±21mmHg,P<0.05)或400pmol(给药前:91±9mmHg比给药后:85±12mmHg,P<0.05),各剂量salusin-α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。侧脑室预先注射MK-801(0.5μmol)、L-NAME(1.15μmol)或Bic(0.3nmol)均不影响侧脑室注射salusin-α产生的降血压效应(P>0.05)。结论侧脑室注射salusin-α显著降低麻醉大鼠的血压,侧脑室注射salusin-α的降压作用可能不是通过NMDA、NO或γ-氨基丁酸通路介导。

Objective To study the central cardiovascular effects of salusin - α by injection of salusin - α into lateral cerebral ventricle （LCV） in anesthetic and artificially respiratory rats. Methods Fifty anesthetized, paralyzed male SD rats were employed in present study. Twenty five of them were randomized into control group （aCSF, n = 4）, salusin -α lOOpmol group （n = 7）, salusin -α 200pmol group （ n = 7） , and salusin - α 400pmol group （ n = 7）. Salusin - α （ 100, 200 or 400pmol） or aCSF was injected into LCV to observe their central cardiovascular effects of central salusin -α. Another twenty five rats, MK -801 （n =7） , L - NAME （n =7） , Bic （n =7） or aCSF （ n = 4） were prior applied into LCV of rats 10min before salusin - α （200pmol） was injected. Results LCV injection of salusin -α produced a significant decrease in BP, but had no significant influence on HR of rats. LCV injection of aCSF didn＇t alter BP or HR in anesthetized rats. The hypotension induced by LCV injection of salusin - α was not significantly inhibited by pretreatment with central application of MK - 801, L - NAME or Bic. Conclusion LCV injection of salusin - α produces hypotension of rats, which is not partly mediated by NMDA, NO or GABA.