Kramer Jay H, Mak I Tong, Phillips Terry M, Weglicki William B
Department of Physiology, George Washington University Medical Center, Washington, DC 20037, USA.
Exp Biol Med (Maywood). 2003 Jun;228(6):665-73. doi: 10.1177/153537020322800604.
Severe dietary Mg restriction (Mg(9), 9% of recommended daily allowance [RDA], plasma Mg = 0.25 mM) induces a pro-inflammatory neurogenic response in rats (substance P [SP]), and the associated increases in oxidative stress in vivo and cardiac susceptibility to ischemia/reperfusion (I/R) injury were previously shown to be attenuated by SP receptor blockade and antioxidant treatment. The present study assessed if less severe dietary Mg restriction modulates the extent of both the neurogenic/oxidative responses in vivo and I/R injury in vitro. Male Sprague-Dawley rats maintained on Mg(40) (40% RDA, plasma Mg = 0.6 mM) or Mg(100) (100% RDA, plasma Mg = 0.8 mM) diets were assessed for plasma SP levels (CHEM-ELISA) during the first 3 weeks and were compared with the Mg(9) group; red blood cell (RBC) glutathione and plasma malondialdehyde levels were compared at 3 weeks in Mg(9), Mg(20) (plasma Mg = 0.4 mM), Mg(40), and Mg(100) rats; and 40-min global ischemia/30-min reperfusion hearts from 7-week-old Mg(20), Mg(40), and Mg(100) rats were compared with respect to functional recovery (cardiac work, and diastolic, systolic, and developed pressures), tissue LDH release, and free radical production (ESR spectroscopy and alpha-phenyl-N-tert butylnitrone [PBN; 3 mM] spin trapping). The Mg(40) diet induced smaller elevations in plasma SP (50% lower) compared with Mg(9), but with a nearly identical time course. RBC glutathione and plasma malondialdehyde levels revealed a direct relationship between the severity of oxidative stress and hypomagnesemia. The dominant lipid free radical species detected in all I/R groups was the alkoxyl radical (PBN/alkoxyl: alpha(H) = 1.93 G, alpha(N) = 13.63 G); however, Mg(40) and Mg(20) hearts exhibited 2.7- and 3.9-fold higher alkoxyl levels, 40% and 65% greater LDH release, and lower functional recovery (Mg(20) < Mg(40)) compared with Mg(100). Our data suggest that varying dietary Mg intake directly influences the magnitude of the neurogenic/oxidative responses in vivo and the resultant myocardial tolerance to I/R stress.
严重的饮食镁限制（Mg(9)，推荐每日摄入量 [RDA] 的9%，血浆镁 = 0.25 mM）会在大鼠中引发促炎神经源性反应（P物质 [SP]），并且先前已表明，体内氧化应激增加以及心脏对缺血/再灌注（I/R）损伤的易感性会因SP受体阻断和抗氧化治疗而减弱。本研究评估了不太严重的饮食镁限制是否会调节体内神经源性/氧化反应的程度以及体外I/R损伤的程度。对维持在Mg(40)（40% RDA，血浆镁 = 0.6 mM）或Mg(100)（100% RDA，血浆镁 = 0.8 mM）饮食的雄性Sprague-Dawley大鼠在最初3周内评估血浆SP水平（化学酶联免疫吸附测定），并与Mg(9)组进行比较；在Mg(9)、Mg(20)（血浆镁 = 0.4 mM）、Mg(40)和Mg(100)大鼠中，在3周时比较红细胞（RBC）谷胱甘肽和血浆丙二醛水平；将7周龄Mg(20)、Mg(40)和Mg(100)大鼠的心脏进行40分钟全心缺血/30分钟再灌注，比较其功能恢复情况（心脏作功、舒张压、收缩压和发展压）、组织乳酸脱氢酶释放以及自由基产生（电子自旋共振光谱法和α-苯基-N-叔丁基硝酮 [PBN；3 mM] 自旋捕获）。与Mg(9)相比，Mg(40)饮食导致血浆SP升高幅度较小（低50%），但时间进程几乎相同。RBC谷胱甘肽和血浆丙二醛水平揭示了氧化应激严重程度与低镁血症之间的直接关系。在所有I/R组中检测到的主要脂质自由基种类是烷氧基自由基（PBN/烷氧基：α(H) = 1.93 G，α(N) = 13.63 G）；然而，与Mg(100)相比，Mg(40)和Mg(20)心脏的烷氧基水平分别高2.7倍和3.9倍，乳酸脱氢酶释放分别增加40%和65%，功能恢复较低（Mg(20) < Mg(40)）。我们的数据表明，不同的饮食镁摄入量直接影响体内神经源性/氧化反应的程度以及由此产生的心肌对I/R应激的耐受性。
