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Effects of Genistein on Physiologic Properties of Isolated Papillary Muscles in Guinea Pigs

Author: GuJing
Tutor: LiHongFang;ZhengTianZhen
School: Lanzhou University
Course: Physiology
Keywords: Genistein 17β-estradiol Electrophysiological properties Contractility Papillary muscle Sarcoplasmic reticulum cAMP
CLC: R285.5
Type: Master's thesis
Year: 2007
Downloads: 3
Quote: 0
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Abstract


Objective: isoflavones phytoestrogens genistein (Genistein, Gen) are mainly derived from the beans, its structural and functional similarity with 17β-estradiol (Est), have weak estrogen-like effects, while is a tyrosine kinase (TK) inhibitor, play the role of cardiovascular protection. One hand, the experimental observation of Gen and Est electrophysiological properties of the guinea pig cardiac excitability, self-discipline, functional refractory period, the positive inotropic effect of Gen myocardial sarcoplasmic reticulum (SR) Li Luoding receptor (RyR) calcium channel SR membrane calcium pump the myocardial membrane Na -Ca to 2 inverse exchange, protein kinase A (PKA) signaling pathway. Methods: Healthy adult guinea pigs, stunning blow its head with a wooden stick, rapid heart was removed and placed through a gas mixture (95% O 2 and 5% CO 2 ) Krebs-Henseleit (KH) solution, prepare specimens, the following experiment: 1, Determination of self-discipline: the Dress Act fixed-rate pacing to observe and record the adrenaline induced self-discipline (Adrenaline Hydrochloride Adr) concentration. 2 the myocardial excitability threshold intensity determination: to test the strength - time curve compared draw the time - intensity curves. 3, the functional refractory period (FRP) Determination: according to the the Govier design method, using the double pulse to stimulate technical determination of functional refractory period (FRP). 4, the myocardial contractility Determination: myocardial resting tension adjusted to 1.0 g, incubated for about 90 minutes, every 15 minutes for KH solution once, when induced by electrical stimulation of the papillary muscle and ventricular muscle rhythmic contraction activity stabilized, start experiment. Myocardial contractile activity using BL-420E bio-signal acquisition system (Chengdu Thai Union Electronics Co., Ltd.) by the computer records. Did not affect the results: First, genistein (Gen) and 17β-estradiol (Est) on the self-discipline of the guinea pig papillary muscle Gen Est concentration of 1 and 10μmol L -1 Adr induced myocardial self-discipline, both in 50μmol · L -1 inhibited self-discipline. Genistein (Gen) and 17β-estradiol (Est) guinea pig papillary muscles the excitability threshold strength of Gen concentration 50μmol · L -1 can be to reduce myocardial excited threshold strength, Gen concentration of 1 and 10μmol L -1 did not affect the excitability threshold intensity, the Est concentration of 1, 10 and 50μmol L -1 does not affect the excitability threshold intensity . Third, genistein (Gen) and 17β-estradiol (Est) on guinea pig papillary muscle FRP Gen concentration 1,10,50 μmol · L -1 and shall not affect myocardial function should not The period; Est concentration 1,10,50 μmol · L -1 and extension of the refractory period of myocardial function. , RyR calcium channel inhibitor role of Gen RyR calcium channel inhibitor ruthenium red (ruthenium red, Ru, 10μmol · L -1 ) and Li Luoding (the ryanodine, Ry, 1nmol · L Gen significantly inhibited the positive inotropic effect, and does not affect the base contracted 20μmol · L -1 Ry base contracted significantly inhibited -1 ), which can be considered Ry basic blocking gyR, this time Gen positive inotropic effect was completely blocked. The cell membrane Na -Ca 2 the inverse exchange, and SR calcium pump inhibitor role of Gen influence of Na of -Ca 2 < / sup> inverse exchange inhibitor Kb-R7943 (the Kb, 1μmol · L -1 ) Gen role without significant impact. SR calcium pump inhibitor by Thapsigargin in (Thap 1μmol, and L -1 ) Gen blocked the positive inotropic effect. Nonspecific M agonist carbachol and PKA inhibitor H-89 Gen role of non-specific M receptor agonist carbachol (Carbachol, Carb, 20μmol · L -1 ) and PKA inhibitor H-89 (2μmol · L -1 ) partially blocked by Gen positive inotropic effect. Conclusion: (1) Gen and Est could decrease myocardial excitability and self-discipline, but Gen enhance its contractile activity, contrary Est role. (2) Gen positive inotropic effect of myocardial cell membrane on Na -Ca 2 inverse exchange has nothing to do, may sarcoplasmic reticulum Ca 2 release and uptake of a direct relationship. (3) Gen positive inotropic effect of cAMP-dependent PKA pathway.

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