Effects of total flavones of Elsholtzia splendens in isolated ischemia/reperfusion rat hearts / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the influence of total flavonoids of Elsholtzia splendens (TFES) on isolated ischemia/reperfusion rat hearts and its underlying mechanisms.</p><p><b>METHODS</b>Hearts isolated from male SD rats were perfused on the Langendorff apparatus and subjected to global ischemia for 30 min followed by 120 min of reperfusion. The cardiac infarct size was measured by TTC staining. Hemodynamic parameters and the level of lactate dehydrogenase (LDH) in the coronary effluent were measured. Absorbance at 520 nm was determined in isolated cardiac mitochondria exposed to 200 micromol/L CaCl2 to detect the opening of the mitochondrial permeability transition pore.</p><p><b>RESULTS</b>Pretreatment with TFES (1, 10, 100 microg/ml) for 5 min decreased infarct size and LDH release and improved the recovery of the left ventricular developed pressure. In mitochondria, the decrease of absorbance at 520 nm evoked by CaCl2 was greatly inhibited by TFES.</p><p><b>CONCLUSION</b>TFES prevents myocardial ischemia/reperfusion injury, and this cardioprotective effect is probably via inhibiting mitochondrial permeability transition pore opening.</p>

Expression and function of autophagy after ischemia/reperfusion in rats hippocampus neuron / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the expression of autophagy after ischemia/reperfusion and its possible function in rats hippocampus neurons.</p><p><b>METHODS</b>After 2 hours oxygen-glucose deprivation and different periods time of reperfusion (OGD/R) treatment in primary hippocampal neurons, neuron viability was evaluated by MTT assay, specific structure of autophagosome and specific protein of autophagy microtubule-associated protein 1 light chain 3 B (LC3B) were detected by transmission electron microscope and immunofluorescence respectively. The inhibitor of autophagy 3-Methyladenine (3-MA) was also used to exam the viability of neurons.</p><p><b>RESULTS</b>Treatment by OGD/R markedly reduced neuronal viability. Compared to the control group, autophagy existed in different time periods after OGD/R shown both in transmission electron microscope and immunofluorescence. Application of 3-MA significantly reduced neuronal viability.</p><p><b>CONCLUSION</b>Oxygen-glucose deprivation can activate autophagy in rat hippocampus neurons, which may resist the injury during ischemia/reperfusion.</p>

Luteolin reduces cardiac dysfunctions in streptozotocin-induced diabetic rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of luteolin (Chinese Traditional Medicine) on cardiac functions and mitochondrial oxidative stress in streptozotocin (STZ)-induced diabetic rats.</p><p><b>METHODS</b>Male SD rats were randomly divided into a normal control group, a luteolin control group, a diabetic group, and diabetic groups orally administered with a low dose (10 mg/(kg x d)) or a high dose of luteolin (100 mg/ (kg x d)) for eight weeks. The body weight, blood glucose, cardiac functions, left ventricular weight, myocardial collagen and reactive oxygen species (ROS) levels were assayed. The cardiac mitochondrial ROS level, superoxide dismutase (SOD) activity and the mitochondrial swelling were measured.</p><p><b>RESULTS</b>Treatment with luteolin had no effect on the blood glucose but reduced the losing of body weight in diabetic rats. High dose of luteolin markedly reduced the ratio of ventricular weight and body weight, increased the left ventricular develop pressure, and decreased the left ventricular end diastolic pressure in diabetic rats. The myocardial levels of ROS and collagen, the cardiac mitochondrial ROS level, and the mitochondrial swelling in diabetic rats were all markedly reduced by high dose of luteolin. Furthermore, high dose of luteolin significantly increased the mitochondrial SOD activity in diabetic rat hearts.</p><p><b>CONCLUSION</b>Treatment with luteolin for 8 weeks markedly improves the cardiac function, which may be related to reducing mitochondrial oxidative stress and mitochondrial swelling in diabetic rats.</p>

Effect of S-allyl-L-cysteine on isolate heart subject to ischemia/reperfusion / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effect of S-allyl-L-cysteine (SAC) on isolated rat heart subject to ischemia/reperfusion(I/R) injury and the mechanisms.</p><p><b>METHODS</b>The isolated perfused rat hearts on a Langendorff apparatus were subjected to global ischemia for 30 min and followed by 120 min of reperfusion. Hemodynamic index, the production of formazan and the level of lactate dehydrogenase (LDH) in the coronary effluent were determined. Superoxide dismutase (SOD) and reactive oxygen species (ROS) in myocardial homogenates were measured.</p><p><b>RESULTS</b>Compared with I/R group, the hemodynamics were greatly improved, the production of formazan was increased, and LDH level in effluent was reduced in SAC group. SAC improved the SOD activity and significantly decreased the level of ROS. In addition, threonine (Thr) attenuated the protective effect of SAC significantly.</p><p><b>CONCLUSION</b>SAC has protective effect against myocardial ischemia/reperfusion injury on rats. The possible mechanism is that SAC be transported into the cell through alanine-serine-cysteine-transporter 1 (ASCT-1) improves SOD activity and reduces the level of ROS.</p>

Electrophysiological effect of atorvastatin on isolated rat hearts injured by ischemia/reperfusion / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the myocardial electrophysiological effect and its underlying mechanisms of atorvastatin (Ator) on isolated rat hearts injured by ischemia/reperfusion (I/R).</p><p><b>METHODS</b>Isolated SD rat hearts were mounted on Langendorff system, and a local I/R was induced by ligation (30 min) and release (15 min) of the left anterior descending artery. During the reperfusion period, the effect of Ator on diastolic excitation threshold (DET), effective refractory period (ERP) and ventricular fibrillation threshold (VFT) on rat heart were measured.</p><p><b>RESULT</b>Compared with the control group, medium concentration of Ator prolonged the ERP in normal rat hearts; low, medium and high concentration of Ator significantly inhibited the decrease of DET, ERP and VFT induced by I/R. However, pretreatment with L-NAME cancelled these cardiac electrophysiological effects of Ator.</p><p><b>CONCLUSION</b>Ator reduced electrophysiological alteration induced by I/R in isolated rat hearts, which may be mediated by activating nitric oxide pathway to enhance the myocardial electrophysiological stability.</p>

Auricularia auricular polysaccharide protects myocardium against ischemia/reperfusion injury / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To determine whether auricularia auricular polysaccharide (AAP) protects heart against ischemia/reperfusion (1/ R) injury and its underlying mechanisms.</p><p><b>METHODS</b>Male Sprague-Dawley rats, pretreated with AAP (50, 100, 200 mg/(kg x d), gastric perfusion) for 4 weeks, were used for Langendorff isolated heart perfusion. The hearts were subjected to global ischemia for 30 min followed by 120 min of reperfusion and the left ventricular hemodynamic parameters were measured. Formazan, a product of 2, 3, 5-triphenyl-tetrazolium chloride (TTC), which is proportional to myocardial viability, was measured at 490 nm, and the level of lactate dehydrogenase (LDH) in the coronary effluent was measured to evaluate the cardiac injury. The cardiac malondialdehyde (MDA), a product of lipid peroxidation, and superoxide dismutase (SOD) activity were determined after myocardial I/R.</p><p><b>RESULTS</b>The pretreatment with AAP at 50, 100, 200/(kg d) for 4 weeks before I/R increased myocardial formazan content, reduced LDH release, improved the recovery of the left ventficular developed pressure, maximal rise rate of left ventricular pressure, and rate pressure product (left ventricular developed pressure multiplied by heart rate) attenuated the decrease of coronary flow during reperfusion. The cardiac protective effect of high dose AAP was more potent than that of compound radix salviae miltiorrhizae (CRSM, 4 ml/(kg x d), gastric perfusion for 4 weeks). Pretreatment with AAP (100 mg/(kg x d)) markedly inhibited the increase of MDA level and the decrease of SOD activity induced by I/R in myocardium.</p><p><b>CONCLUSION</b>The findings indicate that in the isolated rat heart, AAP protects myocardium against ischemia/reperfusion injury via enhancing the activity of SOD and reducing lipid peroxidation in heart.</p>

Vasodilating effect and its mechanism of ethanol on isolated rat thoracic aorta at different resting tension / 中国应用生理学杂志

<p><b>AIM</b>To investigate the vasodilating effect and its mechanism of ethanol on isolated rat thoracic aorta at different resting tension.</p><p><b>METHODS</b>The tension of the isolated Sprague-Dawley rat thoracic aorta rings perfused with different concentrations of ethanol was measured using organ bath technique.</p><p><b>RESULTS</b>At different resting tension (1.0, 1.5, 2.0, 2.5, 3.0, 3.5 and 4.0 g), ethanol (0.1-7.0 per thousand) caused a concentration-dependent relaxation on endothelium-denuded aortic rings precontracted with KCl (6 x 10(-2)mol/L) or phenylephrine (PE, 10(-6) mol/L), and the vasodilating effect was the most potent when the aortic rings were at the resting tension of 3 g. Ethanol had much less vasodilating effect on endothelium-intact aortic rings. Ethanol at 3 per thousand (the maximum-effect concentration) inhibited the CaCl2 induced contraction and downward shifted concentration-response curve of endothelium-denuded aortic rings pre-contracted with KCI or PE at the resting tension of 3 g. Incubation of aorta with ruthenium red (10(-5) mol/L) or heparin (50 mg/L) decreased the vasodilating effect of ethanol (3.0 per thousand) on endothelium-denuded aorta precontracted with PE at the resting tension of 3 g.</p><p><b>CONCLUSION</b>Ethanol induces endothelium-independent relaxation on rat thoracic aorta, which is concerned with the resting tension. This effect of ethanol may be mediated by the inhibition of voltage-dependent and receptor-operated Ca2+ channels in the vascular smooth muscle cells. The inhibition of the ryanodine receptor and trisphosphate inositol (IP3) pathway may also contribute to this effect.</p>

Effect of nitric oxide synthase inhibitors on the changes of hemodynamic parameters and aortic tension induced by septic shock in rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effect of three types of nitric oxide synthase inhibitors on the changes of hemodynamic parameters and thoracic aorta tension induced by septic shock in rats.</p><p><b>METHODS</b>We used cecal ligation and puncture (CLP) method to establish septic shock in rats, and the three types of nitric oxide synthase inhibitors were injected after CLP. The carotid artery was cannulated and connected to a pressure transducer to determine mean arterial blood pressure (MABP). Ventricular dynamic parameters were determined following intraventricular cannulation via the carotid artery, including heart rate (HR), left ventricular developed pressure (LVDP), maximal rise/fall velocity of ventricular pressure (+/- dP/dt(max)). Isolated thoracic rings were mounted on an organ bath and the tension of the vessel was recorded.</p><p><b>RESULTS</b>(1) After using L-NAME, AMG and 7-NI the mortality decreased to 50.0%, 37.5%, and 42.1%, respectively (from 65.2% in septic shock rats); (2) The MABP in septic shock rats partly recovered after using the NOS inhibitors, all ventricular dynamic parameters partly recovered after using the inhibitors; (3) The hyporeactivity of endothelium-denuded aortic rings to vasoconstrictors induced by septic shock was partly recovered by pretreatment with the inhibitors. However, only L-NAME or 7-NI could inhibit the decrease of vasoconstriction induced by septic shock in endothelium-intact aortic rings.</p><p><b>CONCLUSION</b>The three types of nitric oxide synthase inhibitors can improve the hemodynamic parameters and vasoconstriction responsiveness of endothelium-denuded aorta of septic shock rats. Furthermore, L-NAME and 7-NI improve the responsiveness of endothelium-intact aorta.</p>

Vascular effect of extract from mulberry leaves and underlying mechanism / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the vascular activity of extract from mulberry leaves (EML) on rat thoracic aorta and the underlying mechanism.</p><p><b>METHODS</b>Isolated thoracic rings of Sprague-Dawley rats were mounted on the organ bath and the tension of the vessel was recorded.</p><p><b>RESULT</b>(1) EML produced a concentration-dependent vasorelaxation of aorta preconstricted by high K(+) (60 mmol/L) or 10(-6) mol/L phenylephrine (PE) in endothelium-intact and endothelium-denuded arteries. (2) EML at EC(50) concentration reduced the calcium dose-response curve. (3) After incubation of aorta with verapamil, EML induced vasocontraction of aorta preconstricted by PE, which was abolished by ruthenium red.</p><p><b>CONCLUSION</b>The vascular effect of EML is biphasic, the vasorelaxation is greater than the vasocontraction. The vasorelaxation induced by EML may be mediated by inhibition of voltage-and receptor-dependent calcium channels in vascular smooth muscle cells, while the vasocontraction is via activation of ryanodine receptor in endoplasmic reticulum.</p>

Treatment with interleukin-2 ameliorates endothelium-dependent vasorelaxation of aorta in streptozotocin-induced diabetic rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the changes in aortic functions in streptozotocin(STZ)-induced diabetic rats and the effect of interleukin-2 (IL-2) on them, we observed the vasorelaxation of aorta to acetylcholine(ACh) and sodium nitroprusside(SNP).</p><p><b>METHODS</b>Male Sprague-Dawley rats were randomly divided into a normal control group, an IL-2 control group, a diabetic group, and diabetic groups administered with a low dose (5 x 10(3) U x kg(-1) x d(-1), s.c.) or a high dose of IL-2 (5 x 10(4) U x kg(-1) x d(-1), s.c.) for five weeks. Aortic rings were isolated for use in vitro isometric force recording studies, and endothelium-dependent relaxation induced by ACh and endothelium-independent relaxation induced by SNP were measured. The serum nitric oxide (NO) levels and the activities of serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were measured.</p><p><b>RESULTS</b>ACh caused a dose-dependent relaxation that was weakened in the diabetic group. The IL-2 treated groups were less weakened. However, the endothelium-independent relaxation induced by SNP was not significantly different in aortae of all groups. The serum NO levels were significantly increased in diabetic rats treated with IL-2 when compared with diabetic group, but the serum SOD and GSH-PX activities were not improved in diabetic group with IL-2.</p><p><b>CONCLUSION</b>IL-2 can improve the aortic endothelium-dependent relaxation in diabetic rats, which involved the improvement of endothelial function in aorta, other than the alteration of anti-oxidative capacity.</p>

Carvedilol protected diabetic rat hearts via reducing oxidative stress / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Bcl-2 gene has close connection with antioxidant stress destruction in many diseases including diabetes. Carvedilol, an adrenoceptor blocker, also has antioxidant properties. To study the effect of carvedilol on the antioxidant status in diabetic hearts, we investigated carvedilol-administrated healthy and streptozotocin-induced diabetic rats. After small and large dosage carvedilol-administered for 5 weeks, hemodynamic parameters, the levels of malondialdehyde, activities of antioxidant enzymes and expression of Bcl-2 mRNA in the cardiac tissues were measured. The diabetic rats not only had cardiac disfunction, weaker activities of antioxidant enzymes, but also showed lower expression of Bcl-2. Carvedilol treatment increased activities of antioxidant enzymes and expression of Bcl-2 in healthy rats as well as diabetic rats. These results indicated that carvedilol partly improves cardiac function via its antioxidant properties in diabetic rats.

Effect of emodin on NO-cGMP signal pathway in rat vascular endothelium in vitro / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the vasorelaxation effect of emodin and its relationship with NO-cGMP signal pathway.</p><p><b>METHODS</b>Changes of tension of rat thoracic aortic rings were measured by MedLab biologic signal collection system, and the activity of total nitric oxide synthase (tNOS), constitutive NOS (cNOS) and inducible NOS (iNOS) in endothelium after being treated with emodin was determined with nitric acid reductase method.</p><p><b>RESULTS</b>Emodin relaxed the phenylephrine and potasium chlorate induced contraction of aortic rings, either with or without intact endothelium, in a concentration-dependent manner. Pretreatment of no-specific potassium channel blocker strontium chloride (CsCL) could attenuate the vasorelaxation effect of emodin on aortic rings without intact endothelium, but it could not inhibit vasorelaxation of emodin on aortic rings with intact endothelium. This vasorelaxation action of emodin (40 micromol/L) could be partial blocked by NOS inhibitor L-NAME and guanylate cyclase inhibitor ODQ, with the vasorelaxation range dropped to 64.76 +/- 13.73% and 6.28 +/- 4.79% respectively. Moreover, emodin (40 micromol/L) increased iNOS activity significantly.</p><p><b>CONCLUSION</b>The concentration-dependent vasorelaxation effect of emodin might act by activating the NO-cGMP pathway in vascular endothelium.</p>