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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 Salusins is a newly discovered biologically active peptide found in 2003 that is widely present in the hematopoietic, endocrine and central nervous systems to reduce blood pressure and mitogen-like effects. Mature salusins include both salusin-α and salusin-β monomers. Although salusins are widely distributed in the central nervous system of humans and rats, the central cardiovascular effects of salusin-β and their mechanisms have not been well studied. Objective To investigate the central cardiovascular effects of salusin-β and its mechanism by intracerebroventricular administration. Methods Fifty-seven male SD rats were anesthetized by intraperitoneal injection of 1.0 g / kg urethane, artificially ventilated, femoral artery and vein were cannulated and fixed in a stereotaxic instrument. 25 rats were randomly divided into control group (intracerebroventricular injection of artificial cerebrospinal fluid (aCSF), n = 4], salusin-β100 pmol group (n = 7), 200 pmol group (n = 7) . After administration, blood pressure and heart rate were observed. The remaining 32 rats were given the blocker group. The rats were randomly divided into aCSF + salusin-β group (n = 4), N-methyl D-aspartate (NMDA) receptor antagonist MK- 801 + salusin-β group (N = 7), Gicin (GABA) receptor antagonist bicuculline (Bic), the inhibitor of nitric oxide synthase (eNOS) + salusin-β group (n = 7), salusin-α + salusin-β group (n = 7). The first intraventricular injection of MK-801 and other blockers, stable blood pressure after 10min and then intracerebroventricular injection of salusin-β, observed after administration of blood pressure and heart rate changes. Results Intraventricular injection of salusin-β 100 pmol [before administration (99 ± 16) vs (85 ± 16) mmHg after administration, P <0.05] ) mmHg, P <0.05] or 400 pmol [before administration (86 ± 21) vs 73 ± 29 mmHg after administration, respectively), and all doses of salusin-β decreased blood pressure in anesthetized rats, influences. Intracerebroventricular injection of the same amount of aCSF does not have a significant effect on the cardiovascular activity of anesthetized rats. Pretreatment with eNOS inhibitor L-NAME (1.15 μmol) attenuated the antihypertensive effect of intracerebroventricular injection of salusin-β (-6 ± 10 vs -CSF + salusin-β group ± 16) mmHg, P <0.05]. No significant effect of intracerebroventricular injection of MK-801 (0.5 μmol), Bic (0.3 nmol) or salusin-α (200 pmol) Conclusion Intracerebroventricular administration of salusin-β significantly reduces the blood pressure in anesthetized rats. The antihypertensive effect of intracerebroventricular injection of salusin-β may be partly mediated by the nitric oxide pathway.