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淫羊藿苷后处理对心肌缺血再灌注损伤的保护作用研究
目的：观察淫羊藿苷（ icariin，ICA）后处理对心肌缺血／再灌注损伤的保护作用及其可能机制。方法：将24只家兔分为3组：假手术组、I／R组以及ICA后处理组。采用家兔在体模型，家兔麻醉后，开胸短暂结扎冠状动脉左前降支模拟缺血，缺血30min后松开结扎线进行再灌注，再灌注前10min耳缘静脉注射给药。灌注过程中检测左心室内压等心功能指标，再灌注180min后采血检测血清中SOD、MDA；随后处死动物，心脏染色测定心肌梗死面积，检测心肌组织中Bcl－2、Bax蛋白水平。结果：与假手术组比较，I／R组中LVSP、±dp／dtmax下降，LVEDP升高，HR降低；血清中SOD活性降低，MDA含量增高；Bcl－2、Bax蛋白表达量增高（P＜0．01，P＜0．05）。与I／R组比较，ICA后处理组中LVSP、±dp／dtmax升高，LVEDP下降；心梗面积减少；血清中SOD活性增高，MDA含量降低；Bcl－2蛋白表达量增高，Bax蛋白表达量降低，（P＜0．05）。结论：ICA后处理对MIRI造成的心脏损伤具有保护作用，能明显改善心功能各项指标，缩小心梗面积，其保护机制与减轻心肌氧化应激反应、抑制心肌细胞凋亡有关。
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急性桐油中毒导致大鼠心肌损伤的酶组织化学及超微结构观察
目的：探讨急性桐油中毒对心肌的损伤机制。方法：模拟人体桐油中毒方式灌喂大鼠，复制大鼠急性桐油中毒模型。采用光镜，电镜及组织化学方法，观察急性桐油中毒对大鼠心肌的影响。结果：急性桐油中毒心肌明显受损，光镜下细胞及间质水肿，电镜下心肌线粒体肿胀，空泡样变，并有髓样小体形成。组化观察心肌琥珀酸脱氢酶(SDH)活性显著下降，乳酸脱氢酶(LDH)活性有增强趋势。结论：急性桐油中毒通过对心肌细胞线粒体的直接损伤以及对能量代谢的影响而引起心脏功能的明显损害。
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p44/p42 MAPK反义寡脱氧核苷酸对血管紧张素Ⅱ诱导的培养乳鼠心肌细胞肥大反应的抑制作用
AIM: To explore the inhibitory effect of antisense oligonucleotide (ODN) to mitogen activated protein kinase (MAPK) on cardiomyocyte hypertrophy induced by angiotensin Ⅱ (Ang Ⅱ). METHODS: A 17-mer phosphorothioateprotected antisense ODN directed against the initiation of translation sites of the p42 and p44 MAPK isoforms by liposomal transfection was applied to inhibit the translation of p44/p42 MAPK mRNA. The sense and random ODNs to p44/p42MAPK were used as sequence controls. Neonatal cardiac myocytes were exposed to Ang Ⅱ (10 nmol/L) for 5 min and then harvested in lysis buffer for the measurement of the activity and the phosphorylated protein content of p44/p42MAPK that were tested by P-81 phosphocellulose filter paper method and Western blotting, respectively. The rate of protein synthesis by [3H]leucine incorporation and the diameter of cell were measured after exposure to Ang Ⅱ for 24 h and 72 h, respectively. RESULTS: In cardiac myocyte Ang Ⅱ increased p44/p42MAPK activity and phosphorylated protein content by 140 % and 699 %, and also increased [3H]leucine incorporation and cell diameter by 40 % and 27 %. c-fos and c-myc mRNAs were induced significantly after exposure to Ang Ⅱ. Antisense ODN to p44/p42MAPK (0.2 μmol/L) reduced Ang Ⅱ-induced MAPK activity by 30 %,and phophorylated MAPK protein expression by 59 % in cardiac myocyte, and inhibited c-fos and c-myc mRNA expression induced by Ang Ⅱ by 44 % and 43 %, respectively. The diameter and the rate of protein synthesis of cardiac myocyte induced by Ang Ⅱ were decreased by 16 % and 22 % after pretreatment with antisense ODN to p44/p42MAPK. CONCLUSION: Antisense ODN to p44/p42 MAPK inhibited the increase of rate of protein synthesis,and the augmentation of cell diameter and expression of c-fos and c-nyc mRNA induced by Ang Ⅱ in cultured cardiac myocytes, p44/p42 MAPK played a critical role in the hypertrophic response induced by Ang Ⅱ in cultured neonatal rat cardiac myocytes.
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肿瘤坏死因子α对大鼠心室肌细胞钙转运的影响
AIM: To study the effects of tumor necrosis factor-alpha (TNF-α) on calcium movement in rat ventricular myocytes. METHODS: Intracellular free Ca2+ concentration was measured with calcium fluorescent probe Fluo-3/AM and laser confocal microscope. L-type calcium current (Ica,L) was recorded with the whole-cell configuration of the patch-clamp techniques. RESULTS: At 2, 20 and 200 μg/L, TNF-α was found to increase intracellular free Ca2+ concentration in a dose-dependent manner illustrated by the increment of calcium fluorescence density with laser confocal microscope. Nicardipine 0.5 μmol/L slightly attenuated TNF-α-induced response. When the cardiac myocytes were exposed to caffeine (100 mmol/L) for 30 min, TNF-α failed to induce any change of intracellular free calcium. However, it was found that TNF-α inhibited Ica,L in whole-cell patch-clamp experiments. At 2, 20, and 200 μg/L, TNF-α decreased peak Ica,L by 3.9 % (-5.1 pA/pF+0.3 pA/pF vs -4.9 pA/pF+0.2 pA/pF, n=9, P＞0.05), 15.7 % (-5.1 pA/pF+0.3 pA/pF vs -4.3 pA/pF+0.3 pA/pF, n=9, P＜0.05) and 19.6 % (-5.1 pA/pF+0.3 pA/ pF vs -4.1 pA/pF+0.4 pA/pF, n=9, P＜0.01), respectively. It shifted the steady-state inactivation curve of Ica,L to the left (V1/2 shifted from -28.7 mV+0.3 mV to -37.8 mV+1.4 mV, n=7, P＜0.05), while it took no effects on steadystate activation and recovery from inactivation. CONCLUSION: TNF-α inhibited Ica,L in rat ventricular myocytes,while increasing the intercellular free Ca2+ level due to the release of Ca2+ from intracellular stores.
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葛根素抑制大鼠心室肌细胞的钠电流
AIM: To study the effect of puerarin (Pue) on Na+ channel in rat ventricular myocytes. METHODS: Whole-cell patch-clamp technique was applied on isolated cardiomyocytes from rats. RESULTS: Pue inhibited cardiac INa in a positive rate-dependent and dose-dependent manner, with an IC50 of 349 μtmol/L. The kinetics of blockage ofcardiac sodium channel by Pue resembled the ClassIa/Ic of antiarrhythmic agents. Pue 300 μmol/L did not alter the shape of the I-V curve of INa, but markedly shifted the steady-state inactivation curve of INa towards more negative potential by 15.9 mV, and postponed the recovery of INa inactivation state from (21.9+ 1.6) ms to (54.4+3.4) ms (P＜0.01). It demonstrated that the steady state of inactivation was affected by Pue significantly. CONCLUSION:Pue protected ventricular myocytes against cardiac damage and arrhythmias by inhibiting recovery from inactivation of cardiac Na+ channels.
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