粉防己碱改善维生素 D_3引起的钙超载大鼠的心肌顿抑(英文)

Tetrandrine improves myocardial stunning in vitamin D_3-induced calcium overload rats

目的 :探讨大鼠钙超载心肌顿抑时心脏收缩功能的变化及粉防己碱 (Tet)的保护作用。方法 :将 46只成年 SD大鼠随机分成对照、心肌缺血、心肌顿抑、大剂量和小剂量 Tet组 ,另 10只大鼠用于确定钙超载。给大鼠注射维生素 D3(Vit D3,30万 U/ kg)和烟酸 ,16 d后检测心肌细胞 Ca2 +浓度 ([Ca2 + ]i)。确认达到钙超载标准后 ,结扎左前降支 ,至 2 0 min心肌缺血 +6 0min再灌注 ,动态监测 dp/ dtmax和 Vmax,实验结束后测定各组心肌 [Ca2 + ]i。 Tet组在注射 Vit D3的同时及以后每日分别给予Tet6 2 .2和 93.6 μmol/ kg,(灌胃 ) ,16 d后 ,致心肌缺血和再灌注 ,测定心肌收缩功能和 [Ca2 + ]i。结果 :给 Vit D3后第 16天 ,[Ca2 + ]i较对照水平增加 2 .6倍 [(146 .8± 10 .8)对 (36 8.5± 2 2 .6 ) nm ol/ L ,(P <0 .0 1) ];Tet组 ,分别为 (2 10 .8± 16 .4)和(198.6± 15 .3) nmol/ L ,明显低于钙超载组 (P<0 .0 1)。缺血前钙超载组心脏收缩功能明显低于对照组 (dp/ dtmax和 Vmax分别为对照组的 76 .6 %和 6 8.4% )。 2 0 m in心肌缺血致各组 dp/ dtmax和 Vmax均明显下降 (P<0 .0 1) ,以顿抑组和钙超载组最为明显。再灌注后心肌收缩功能逐步恢复。在 Tet组 ,各时间点 dp / dtmax和 Vmax均高于顿抑组和钙超载组 。

Objective: To investigate the changes of myocardial contractile function during myocardial stunning in calcium overload rats and the protective effects of tetrandrine. Methods: Forty six rats were randomized into control, myocardial ischemia, myocardial stunning, low and high dose of tetrandrine groups. Another 10 rats were used to identify the calcium overload. vitamin D 3 (0.3 million Unit/kg) and nicotinic acid were administered. After 16 d when calcium overload occured, left anterior descending artery was ligated. Twenty minutes of myocardial ischemia followed by 60 min of reperfusion was induced. The contractile function parameters were determined dynamically. At the end of experiment, myocardial cytosolic [Ca 2+ ]i was determined in various groups. In tetrandrine groups, tetrandrine (62.2 or 93.6 μmol/kg ) was administered by gastrogavage daily.After 16 d, the rats undergone the experiments mentioned above. Results: Sixteen days after vitamin D 3, nicotinic acid were given, [Ca 2+ ]i increased by 2.6 folds (146.8±10.8) vs (368.5±22.6) nmol/L, ( P <0.01). Whereas, [Ca 2+ ]i in tetrandrine groups were (210.8±16.4) and (198.6±15.3) nmol/L, which were significantly lower than that of calcium overload group. Twenty minutes of myocardial ischemia resulted in the decrease of dp/dtmax and Vmax in all groups with the most significant in stunning and calcium overload groups. The contractile function restored gradually after reperfusion. At all time points, dp/dtmax and Vmax in both tetrandrine groups were higher than those in both stunning and calcium overload groups. And effect with higher dose of tetrandrine were more significant than in low dose of tetrandrine. After 60 min of reperfusion, dp/dtmax in stunning, calcium overload, low and high dose of tetrandrine groups were 49.7%, 51.5%, 71.0% and 83.4% of that in control, respectively, and Vmax were 55.0%, 49.8%, 73.9% and 77.5% of that in control, respectively. Conclusion: The myocardial contractile function in vitamin D 3 induced calcium overload group is impaired. On basis of myocardiocyte calcium overload, transient ischemia leads to myocardial stunning. At the stage of ischemia, the impaired degree of myocardial contractile function is similar to that in stunning group, suggesting at this stage the effect of ischemia on myocardial function is greater than that of calcium overload. Tetrandrine chronically improves the myocardial function in Vitamin D 3 induced calcium overload rats. [