The cardioprotective effect and mechanism of lumbrokinase / 药学学报

<p><b>AIM</b>To investigate the protective effect of lumbrokinase against myocardial ischemia and to further explore its underlying mechanisms.</p><p><b>METHODS</b>The effect of lumbrokinase on myocardial ischemia was observed by a model of acute myocardial infarction due to permanent ligation of the left anterior descending coronary artery in rats. Patch-clamp technique and laser scanning confocal microscopy were utilized to study the action of lumbrokinase on L-type calcium current (ICa-L) and intracellular calcium concentration ([Ca2+]i).</p><p><b>RESULTS</b>Lumbrokinase decreased the infarct size of myocardium in a dose-dependent manner. The inhibitory rate of lumbrokinase at the dose of 20, 40 and 80 mg x kg(-1) was 7.7%, 34.6% and 46.2%, respectively. The electrophysiological studies displayed that, at + 10 mV, the ICa-L was markedly reduced from (-14.42 +/- 1.53) pA/pF to (-11.33 +/- 1.40) pA/pF (decreased by 21.4%, P <0.01) and (-9.92 +/- 1.31) pA/pF (decreased by 36.5%, P <0.01) by lumbrokinase (10 and 50 micromol x L(-1)), respectively. Confocal experiments showed that 10 micromol x L(-1) lumbrokinase showed no obvious effects on [Ca2+]i at resting states (P > 0.05). However, the increase of [Ca2+]i induced by 60 mmol x L(-1) KCl was distinctly limited by 10 micromol x L(-1) lumbrokinase (P <0.01). Within 240 s, the no obvious peak value of fluorescent intensity (FI) was shown.</p><p><b>CONCLUSION</b>Lumbrokinase showed protective action against myocardial infarction in rats. The possible mechanisms of anti-ischemia could be attributed to decreasing ICa-L and [Ca2+] of ventricular myocytes in rats.</p>

Establishment of a novel arrhythmia model in rats / 药学学报

<p><b>AIM</b>To establish a novel arrhythmia model in rats.</p><p><b>METHODS</b>Coronary artery occlusion was produced in hyperlipidemic rats after the animals were fed a high fat and cholesterol chow for 15 days. The incidence, duration and score of arrhythmias were determined 1 hour after coronary occlusion.</p><p><b>RESULTS</b>The incidence, duration and score of arrhythmia induced by coronary artery occlusion increased significantly in hyperlipidemic rats compared with those in normal rats (P < 0.05). In normal rats, pretreatment with amiodarone 60 mg x kg(-1) or verapamil 25 mg x kg(-1) 3 days before coronary artery occlusion did not influence the incidence, duration and score of arrhythmia (P > 0.05). In hyperlipidemic rats, amiodarone 60 mg x kg(-1) decreased the incidence, duration and score of arrhythmia (P < 0.05), but not verapamil 25 mg x kg(-1) (P > 0.05).</p><p><b>CONCLUSION</b>The novel arrhythmia model induced by coronary artery occlusion in hyperlipidemic rats is reliable and similar to the pathophysiological state in human being.</p>

Inhibitory effects of chloride channel blockers NPPB on proliferation of human glomerular mesangial cells / 药学学报

<p><b>AIM</b>To investigate the effects of NPPB, a chloride channel blocker, on proliferation of mesangial cells.</p><p><b>METHODS</b>Cell proliferation was determined by measuring cell number and 3H-thymidine incorporation. The LDH activity released from these cells was measured as evaluation of cell viability. The phase of cell cycle was detected by flow cytometry.</p><p><b>RESULTS</b>Cell proliferation assays showed that treatment with both NPPB (50 and 25 micromol x L(-1)) and in hypertonic media (100% increased osmolarity with D-mannitol ) significantly reduced the number of human MC and 3H-thymidine incorporation in a dose-dependent manner. But the LDH activity was not significantly altered in the treatment with 50 micromol x L(-1) NPPB. Flow cytometry experiments showed that 50 and 25 micromol x L(-1) NPPB arrested (84.2 +/- 2.4) % and (80.8 +/- 2.9) % of cells at G0/G1 stage, versus (70.5 +/- 1.4) % of control cells. Conclusion NPPB suppresses cell proliferation and produces growth arrest at G0/G1 phase in human MC by a mechanism probably associated with changes in cell volume.</p>

M3-R/IK(M3)--a new target of antiarrhythmic agents / 药学学报

<p><b>AIM</b>To investigate the relationship between M3-R/IK(M3) and arrhythmia in order to find a new target for antiarrhythmic agents.</p><p><b>METHODS</b>Using the acute ischemic model of rats and patch-clamp techniques, the effects of the M3 receptor on the occurrence of arrhythmias and its possible mechanisms were studied.</p><p><b>RESULTS</b>In acute ischemic model of rats, the M3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine-methiodide (4DAMP) increased the occurrence of arrhythmias, and the M3 receptor agonist choline suppressed the onset and the development of arrhythmias (P < 0. 01). No change was observed after treatment with other receptor antagonists (M1, M2, and M4). With patch-clamp techniques, it was found that choline induced K+ current could be inhibited by 4DAMP. Antagonists toward M1, M2, and M4 receptors all failed to alter the current.</p><p><b>CONCLUSION</b>Choline modulates the cellular electrical properties of the heart, probably by activating a K+ current via stimulation of the M3 receptor. M3-R/IK(M3) may act as a new target for antiarrhythmic agents.</p>