The effects of Shadu Cao Mixture on immune functions of immunosuppression mice / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Shadu Cao Mixture (SDCM, traditional Chinese medicine) on immune functions of immunosuppression mice.</p><p><b>METHODS</b>Fifty BALB/C mice were randomly divided into blank control group, model group, SDCM low-dose, middle-dose and high-dose group. Except the blank control group, other groups were intraperitoneal injected with cyclophosphamide (40 mg/kg) to establish immunosuppression mice model. The blank control group and model group received gavage administration with nonnal saline, while the other groups received gavage administration with different doses of SDCM (10, 20, 40 m/kg for 15 days) respectively. The number of leukocytes and serum levels of interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in peripheral blood, spleen index, and the function of NK cells were measured.</p><p><b>RESULTS</b>Compared with the model group , SDCM increased the number of leukocytes and serum concentrations of IL-2, TNF-α and IFN-γ in peripheral blood and improved the spleen index and the function of NK cells significantly (P < 0.05-0.01).</p><p><b>CONCLUSION</b>SDCM could remarkably enhance the immune functions of immunosuppression mice induced by cyclophosphamide.</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>

Study of the effects of Auricularia auricular polysaccharide on local ischemia/reperfusion injury in rat / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the influence of Auricularia Auricular polysaccharide (APP) on acute cerebral injury induced by ischemia/reperfusion in rats and its underlying mechanism.</p><p><b>METHODS</b>Adult male SD rats were intragastrically pretreated with AAP at a low (50 mg/kg) or high (100 mg/kg) dose once a day for 20 days before operation. Rats intraperitoneally injected with ginkgo biloba extract (EGb671) were taken as positive control. Focal ischemia was achieved by middle cerebral artery occlusion (MCAO) on the right side for 60 min. After 24 hrs of reperfusion, the nerve function defects were recorded by Longa's score and the brain infarct sizes were measured by 2,3,5-Triphenyl-tetrazolium-chlor (TTC) staining. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining after 48 h of reperfusion. The levels of oxidative stress was determined via the mitochondria-generated reactive oxygen species (ROS).</p><p><b>RESULTS</b>AAP treatment decreased Longa's score, brain infarct size, apoptotic neurons and mitochondria-generated ROS in a dose-dependent manner. AAP at 100 mg/kg gave a better performance compared with EGb671 on all parameters examined.</p><p><b>CONCLUSION</b>AAP treatment protected rat brain from focal ischemia/reperfusion injury by its anti-oxidative effect and worked better than EGb671.</p>

The alterations of nitric oxide synthase activity of ventricular cardiac muscle of rats in two septic shock models / 中国应用生理学杂志

<p><b>AIM</b>To observe the differences of hemodynamics and nitric oxide synthase(NOS) activity of ventricular cardiac muscle in two septic shock models and explore the possible mechanism.</p><p><b>METHODS</b>Two rat models of septic shock[lipopolysaccharide(LPS)-induced and cecal ligation and puncture (CLP)-induced septic shock] were used. The hemodynamic parameters and nitric oxide synthase activity of ventricular cardiac muscle were measured.</p><p><b>RESULTS</b>The hemodynamic parameters in CLP-induced model were increased in the early stage and decreased in the late stage while in LPS-induced model the parameters showed the same change of the CLP late stage. Both LPS model and CLP model (late stage) showed significant increase in NOS activity, but there was no difference between the two models. After treatment of the NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME), the parameters of CLP-late stage and LPS model increased significantly. The NOS activity reached the highest level in the CLP-middle stage. The production of nitrite/nitrate decreased significantly in LPS model and CLP model(late stage) after treatment of L-NAME, but the nitrite/nitrate produced by constitutive NOS in LPS model was higher than CLP model(late stage).</p><p><b>CONCLUSION</b>The increase of the NOS activity may be the main reason to lead to the depression of the hemodynamic parameters. Inducible NOS may play the leading role in the LPS model while cNOS and iNOS have the same effect in the CLP model.</p>

Experimental studies on antiarrhythmic effect of jumi extraction / 中国应用生理学杂志

<p><b>AIM</b>To investigate the antiarrhythmic effect of jumi (JM) extraction.</p><p><b>METHODS</b>The conventional antiarrhythmic methods were used.</p><p><b>RESULTS</b>Administration of JM extraction reduced the occurrence of ventricular fibrillation induced by chloroform in a dose-dependent manner in mice. Quinidine significantly decreased the number of ventricular premature beats and ventricular tachycardia, shortened the duration of arrhythmia in aconitine-treated rats. But JM extraction had no effect on aconitine-induced arrhythmia. Compared with control, arrhythmia score was lower in ischemia/reperfusion rats which pretreated with 2.0 g/kg of JM extraction.</p><p><b>CONCLUSION</b>JM extraction has obvious protection effects in chloroform- and ischemia-induced arrhythmia, but has no effect in aconitine-induced arrhythmia.</p>

Cardioprotective effect of ischemic postconditioning and preconditioning against prolonged ischemia and reperfusion induced injury in isolated rat heart / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To explore the cardioprotection effect of co-treatment with ischemic postconditioning and preconditioning in ischemia/reperfusion (I/R) injury and the related mechanism.</p><p><b>METHODS</b>Male Sprague-Dawley rats were used for Langendorff isolated heart perfusion. The hearts were subjected to global ischemia for 60 min followed by 120 min of reperfusion. The cardiomyocyte viability was measured by MTT-formazan method, and the cardiac injury was evaluated by the levels of lactate dehydrogenase (LDH) in the coronary effluent. Ventricular hemodynamic parameters were also measured.</p><p><b>RESULT</b>In 60 min of ischemia and 120 min of reperfusion group, ischemic postconditioning increased formazan content, reduced LDH release, but hemodynamic parameters did not improved. Co-treatment with ischemic postconditioning and preconditioning during the prolonged ischemia further improved the hemodynamic parameters. The calcium activated potassium channel antagonist paxilline attenuated the effect of co-treatment with ischemic postconditioning and preconditioning.</p><p><b>CONCLUSION</b>Ischemic postconditioning and preconditioning may synergically protect myocardium from severe ischemia injury, which may be related to calcium-activated potassium channel.</p>

Kappa-opioid receptor mediates the cardioprotective effect of ischemic postconditioning / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of kappa-Opioid receptors in the cardioprotection elicited by ischemic postconditioning and the underlying mechanism.</p><p><b>METHODS</b>The isolated perfused hearts of male Sprague-Dawley rats were subjected to 30 min of global ischemia followed by 120 min of reperfusion. formazan content of myocardium was measured spectrophotometrically, and the level of lactate dehydrogenase (LDH) in the coronary effluent was also measured. In isolated ventricular myocytes hypoxia postconditioning was achieved by 3 cycles of 5 min reoxygenation/5 min hypoxia starting at the beginning of reoxygenation, and cell viability was measured.</p><p><b>RESULT</b>In the Langendorff perfused rat heart model, ischemic postconditioning (6 cycles of 10 s reperfusion/10 s global ischemia starting at the beginning of reperfusion) increased formazan content, reduced LDH release, improved the recovery of the left ventricular developed pressure, maximal rise/fall rate of left ventricular pressure, left ventricular end-diastolic pressure and rate pressure product (left ventricular developed pressure multiplied by heart rate), attenuated the decrease of coronary flow during reperfusion and increased the isolated cell viability. Pretreatment with nor-BNI, an antagonist of kappa-Opioid receptors and mitoK(ATP) blocker 5-HD attenuated the effect of ischemic/hypoxic postconditioning.</p><p><b>CONCLUSION</b>Postconditioning may protect myocardium against ischemia/reperfusion injury via activating kappa-Opioid receptors and mitoK(KATP).</p>

Role of mitochondrial calcium uniporter in myocardial hypoxia/reoxygenation induced injury / 中国应用生理学杂志

<p><b>AIM</b>To investigate the role and mechanism of mitochondrial calcium uniporter (MCU) in myocardial hypoxia/reoxygenation injury.</p><p><b>METHODS</b>Isolated rat hearts were perfused with Langendorff apparatus. The hypoxia/reoxygenation injury was achieved by ligation of left anterior coronary artery for 30 min followed by release of ligation for 120 min. The left ventricular developed pressure (LVDP), the maximum rise/fall rate of left ventricular pressure (+/- dP/dt(max)), and the left ventricular end-diastolic pressure (LVEDP) were recorded. Activities of lactate dehydrogenase (LDH) in coronary effluent and reactive oxygen species (ROS) of myocardial mitochondria were spectrophotometrically assayed. Infarct size was determined by TTC staining method.</p><p><b>RESULTS</b>Compared with the hypoxia/reoxygenation (H/R) group, ruthenium red (RR, 5 micromol/L), given at the on set of reoxygenation, significantly improved the contractile function of left ventricle, decreased the myocardial infarct size, alleviated the production of ROS in myocardial mitochondria and LDH release in coronary effluent. Spermine (20 micromol/L), given at the onset of reoxygenation, enhanced the production of ROS in the mitochondria and LDH release in coronary effluent at 5, 20 and 30 min of reoxygenation, however, there were no significant differences of ventricular contractile parameters and infarct size between groups subjected to hypoxia/reoxygenation with or without spermine treatment. Co-treatment of ROS scavenger N-2-mercaptopropionyl glycine (1 mmol/L) with spermine abolished the effect of spermine.</p><p><b>CONCLUSION</b>Inhibition of mitochondrial calcium uniporter may refrain heart from hypoxia/reoxygenation injury via decreasing the production of ROS in heart mitochondria.</p>

Cardioprotection of mitoSlo1 channel activation involves mitochondrial permeability transition in ischemia and reperfusion of rat hearts / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate whether the cardioprotection of mitochondrial Slo channel (mitoSlo(1) channel) is associated with mitochondrial permeability transition in isolated rat hearts subjected to ischemia and reperfusion.</p><p><b>METHODS</b>Isolated perfused rat hearts were subjected to 30 min regional ischemia (occlusion of left anterior descending artery) and 120 min reperfusion. The infarct size, lactate dehydrogenase (LDH) release during reperfusion and ventricular hemodynamic parameters were measured.</p><p><b>RESULTS</b>Pretreatment with mitoSlo(1) channel opener, NS1619 10 micromol/L for 10 min reduced the infarct size and LDH release, and improved the recovery of left ventricular developed pressure, left ventricular end-diastolic pressure, maximal rise/fall rate of left ventricular pressure and coronary flow during reperfusion. Administration of atractyloside (20 micromol/L), an opener of mitochondrial permeability transition pore, for 20 min (last 5 min of ischemia and first 15 min of reperfusion) attenuated the reduction of infarct size and LDH release and improvement of left ventricular performance induced by NS1619. In the isolated mitochondria, a significant inhibition of Ca(2+)-induced swelling was observed when mitochondria were incubated with NS1619.</p><p><b>CONCLUSION</b>MitoSlo(1) channel activation by NS1619 protects the myocardium against ischemia and reperfusion injury by inhibiting mitochondrial permeability transition pore opening.</p>