N-n-butyl haloperidol iodide protectsH9c2 cardiac myocytes against hypoxia/reoxygenationinjury through mitochondria-dependent apoptotic pathway / 中国药理学通报

Aim To investigate the effect of N-n-butyl haloperidol iodide(F2) on mitochondria-dependent apoptotic pathway of H9c2 cardiac myocytes during hypoxia/reoxygenation(H/R) injury.Methods The H/R models of H9c2 cardiac myocytes were established.The H9c2 cardiac myocytes were randomly divided into five groups: control group(C group), hypoxia/reoxygenation group(H/R group), F2 low concentration group(L), F2 medium concentration group(M), F2 high concentration group(H).Apoptotic rate was evaluated by flow cytometry(FCM).The levels of Cyto C, Bcl-2, Bax were observed by Western blot.Caspase-3 activity was measured with colorimetry.Results Compared with H/R group, F2 low, medium and high concentrations group could significantly decrease apoptosis rate and increase the ratio of Bcl-2 to Bax proteins and inhibit the release of Cyto C into the cytosolic fraction, and decrease caspase-3 activity.Conclusion F2 can protect H9c2 cardiac myocytes against H/R-induced injury through interfering in mitochondria-dependent pathway.

Calcium antagonists protect cardiac microvascular endothelialcells against hypoxia/reoxygenation injury through iPLA2 / 中国药理学通报

Aim To investigate the effects of classic calcium antagonists verapamil(Ver),nifedipine(Nif),diltiazem(Dil)and the novel calcium antagonist N-n-butyl haloperidol iodide(F2)which was synthesized by our lab by regulating Ca2+-independent phospholipase A2(iPLA2)on hypoxia/reoxygenation(H/R)injury of cardiac microvascular endothelial cells(CMECs)and the mechanisms.Methods The CMECs were isolated from SD neonatal rats.The H/R model was established,then cells were treated with different concentrations of calcium antagonists and F2.The content of LDH in the cell supernatant was measured by colorimetric method.The levels of IL-6 and AA in cell supernatant were measured by ELISA;and late-stage apoptosis was measured by TUNEL.The mRNA and protein expression levels of iPLA2 in CMECs were examined by real time-PCR and Western blot analysis.Results Calcium antagonists except Dil decreased the generation of LDH,IL-6 and AA in a dose-dependent manner(P<0.05),and reduced the apoptosis(P<0.05).F2 and Ver decreased the mRNA and protein expression of iPLA2 in a dose-dependent manner,while there were no such effects for Nif and Dil.Conclusions Calcium antagonists except Dil have protective effects against H/R injury.F2 and Ver protect CMECs against H/R injury partly through iPLA2.

Effect of N-n-butyl haloperidol iodide on potassium channel in smooth muscle cells and rings of rat aorta / 中国药理学通报

AIM To investigate the effect of N n butyl haloperidol iodide (F 2) on potassium currents in enzymatically isolated vascular smooth muscle cells (VSMC) from thoracic aortas and the effect of F 2 on aortic rings of rat. METHODS The whole cell patch clamp technique and the contraction of rats thoracic aortic rings were used in experiments. RESULTS The outward currents were observed when holding potential was -40 mV and the cell was depolarized from -30 mV to +100 mV (in 10 mV increase) for 400 ms. At the point of the test potential of +70 mV, solutions of F 2 (0 1,1, 5 ?mol?L -1 ) were added into bath (external) solution, which led to the increase of the outward currents from (229?28)pA,(226?57)pA and(228?42) pA to (354?29) pA ( n =6, P