Effects of EPO on expression of TGF-β1 and ColⅠin myocardium of liver cirrhosis rats / 中国药理学通报

Aim To observe the effects of liver cirrho-sis on the expression of transforming growth factor-β1 ( TGF-β1 ) and ColⅠin rat myocardium and interven-tion of erythropoietin ( EPO ) . Methods Thirty-six male Sprague-Dasley rats were randomly divided into three groups:control group, liver cirrhosis group and EPO group, then the cardic hemodynamic parameters in vivo and levels of serum lactate dehydrogenase ( LDH ) as well as creatine kinase isoenzyme ( CK-MB) were measured. With Masson′s trichrome stain, changes of collagen formation of myocardial tissue in different groups were observed. Also the mRNA ex-pressions of TGF-β1 and ColⅠin myocardium were de-tected by RT-PCR. Results In contrast to control group, rats in liver cirrhosis group showed a decline in systolic and diastolic function of left ventricule, rising myocardial enzyme, a distinct increase of cardiac colla-gen deposition, as well as an elevation of TGF-β1 and ColⅠmRNA expressions. In contrast to liver cirrhosis group, rats in EPO group demonstrated an improve-ment in systolic and diastolic function of left ventricule as well as in cardiac collagen deposition, and a de-crease in both myocardial enzyme and TGF-β1 and ColⅠmRNA expressions. Conclusion Liver cirrhosis can lead to the changes of myocardial structure and function in rats,and it can accelerate myocardial inter-stitial fibrosis; EPO can protect the myocardial injury in liver cirrhosis rats.

Protective effects of hydrogen sulfide on diaphragmatic muscle of Type 1 diabetic rats and its anti-apoptotic mechanisms / 中南大学学报(医学版)

OBJECTIVE@#To explore the protective effects of hydrogen sulfide (H2S) on diaphragmatic muscle of Type 1 diabetic rats and its anti-apoptotic mechanism.
@*METHODS@#Thirty male Sprague Dawley rats were randomly divided into a control group, a diabetes group and a treatment group (n=10 per group). Streptozotocin (i.p.) was utilized to establish a rat model of Type 1 diabetes mellitus (DM). The DM rats were treated with NaHS solution (i.p.). After 8 weeks, the diaphragmatic muscle contractility was assessed by isolated diaphragmatic strips experiments. The peak twitch tension (Pt), maximum tetanic tension (Po), time to peak contraction (CT), half relaxation time (1/2RT) and maximal rates of contraction/relaxation (±dT/dtmax) were measured. The alterations of diaphragmtic ultrastructure were observed by electron microscopy. The content of malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and caspase-3 were analyzed by spectrophotometric method. The expressions levels of Bcl-2 and Bax mRNA in diaphragmatic muscle were detected by RT-PCR.
@*RESULTS@#Compared with the control group, in the diabetic group, the Pt, Po and ±dT/dtmax were significantly reduced (all P<0.01), while CT and 1/2RT were significantly increased (both P<0.01); ultrastructure in the diaphragmatic muscle were obviously changed; the content of MDA and the activity of caspase-3 were increased (both P<0.01), while the activity of SOD was decreased (P<0.01); the ratio of Bcl-2/Bax at mRNA level was decreased (P<0.01). Compared with the diabetes group, in the treatment group, the diaphragm contractility and ultrastructural damage were improved; the content of MDA and the activity of caspase-3 were decreased (P<0.05, P<0.01 respectively), while the activity of SOD was increased (P<0.01), the ratio of Bcl-2/Bax at mRNA level was also increased (P<0.01). 
@*CONCLUSION@#The exogenous H2S can protect diaphragmatic muscle of Type 1 diabetic rats, which is related to reducing oxidative damage and suppressing cell apoptosis.

Negative Modulation of NO for Diaphragmatic Contractile Reduction Induced by Sepsis and Restraint Position / 法医学杂志

In practice of forensic medicine, potential disease can be associated with fatal asphyxia in re-straint position. Research has demonstrated that nitric oxide (NO) and nitric oxide synthase (NOS) are plentifully distributed in skeletal muscle, contributing to the regulation of contractile and relaxation. In the current study, respiratory functions, indices of diaphragmatic biomechanical functions ex vivo, as well as NO levels in serum, the expressions of diaphragmatic inducible NOS (iNOS) mRNA, and the effects of L-NNA on contractility of the diaphragm were observed in sepsis induced by cecal ligation and punc-ture (CLP) under the condition of restraint position. The results showed that in the CLP12-18 h rats, respiratory dysfunctions; indices of diaphragmatic biomechanical functions (Pt, +dT/dtmax, -dT/dtmax, CT, Po, force over the full range of the force-frequency relationship and fatigue resistance ) declined progressive-ly; the NO level in serum, and iNOS mRNA expression in the diaphragm increased progressively; force increased significantly at all stimulation frequencies after L-NNA pre-incubation. Restraint position 1 h in CLP12 h rats resulted in severe respiratory dysfunctions after relative stable respiratory functions, almost all the indices of diaphragmatic biomechanical functions declined further, whereas little change took place in NO level in serum and diaphragmatic iNOS mRNA expression; and the effects of L-NNA were lack of statistical significance compared with those of CLP12 h, but differed from CLP18 h group. These results suggest that restraint position and sepsis act together in a synergistic manner to aggravate the great reduction of diaphragmatic contractility via, at least in part, the negative modulation of NO, which may contribute to the pathogenesis of positional asphyxia.

Practice and thinking on combination of basic and clinic medicine during pathophysiology teaching process / 中华医学教育探索杂志

The relatively independence and separation in the teaching of clinical medicine and basic medicine limits the ability training of students,and the combination of basic and clinic medicine in teaching has become the core issues and trends in medical teaching reform.So the conventional teaching patterns were reformed in pathophysiology by applying combination of basic and clinic medicine in teaching.In order to accelerate medical students to early exposure to clinical medicine Bengbu medical college changed the teachers' teaching ideas,promoted the local integration of the courses of basic and clinical medicine and the combination of basic and clinic medicine teachers in teaching,reformed mechanisms in teaching management and teaching operation.We also tested the preliminary reform effects by way of students' evaluation of the teaching and examination,and discussed the unfavorable factors affecting the educational reform and thought out some countermeasures.

Calcium activated potassium channel and protein kinase C participate in the cardiac protection of remote post conditioning

The present study was designed to investigate the roles of Ca[2+] activated K[+] channel [KCa] and protein kinase C [PKC] in the protective mechanisms of remote ischemic post conditioning [RPostC] when rat heart was subjected to ischemia/reperfusion [I/R] injury in vivo. Rat heart was subjected to regional ischemia for 45 min and reperfusion for 180 min in vivo to mimic I/R injury. RPostC was induced by 5 min right femoral artery occlusion followed by 5 min reperfusion for 3 cycles [totally 30 min] after 15 min of cardiac ischemia. Delayed remote ischemic post conditioning [delayed RPostC] was induced after 10 min of cardiac reperfusion. The hemodynamic parameters including mean arterial blood pressure and heart rate [HR] were recorded, and lactate dehydrogenase [LDH] release in plasma and infarct size were determined, and arrhythmia scores were calculated. In contrast to I/R, RPostC reduced infarct size and LDH release during reperfusion, the occurrence of arrhythmia was decreased, but no changes in delayed RPostC. The specific inhibitor of KCa iberiotoxin and PKC inhibitor chelerythrine both attenuated the role of RPostC. The findings indicated that RPostC had a protective effect on myocardial ischemia/reperfusion injury. Opening of KCa and activating of PKC may be involved in the mechanisms of RPostC

Changes of sarcoplasmic reticulum calcium ATPase, titin, and nebulin expressions in the diaphragm of rats with liver cirrhosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the molecular mechanisms of diaphragm injury in rats with liver cirrhosis.</p><p><b>METHODS</b>Thirty adult male Sprague-Dawley rats were randomized into control group (n=10) and carbon tetrachloride-induced liver cirrhosis group (LC group, n=20). In the 9th week, the rat body weight and diaphragm to body weight ratio were measured, and the parameters of diaphragm contractility including peak twitch tension (Pt), maximum tetanic tension (Po), time to peak contraction (CT), half relaxation time (1/2RT), and force-frequency curve were assessed using a Medlab-U/4C biological signal collecting system. The activities of superoxide dismutase (SOD), succinic dehydrogenase (SDH) and myeloperoxidase (MPO) and malondiadehyde (MDA) content in the diaphragm were detected. The mRNA expression levels of sarcoplasmic reticulum calcium ATPase (SERCA) and cytoskeletal proteins (titin and nebulin) in the diaphragm were detected by RT-PCR, and the diaphragm ultrastructure was examined with electron microscopy.</p><p><b>RESULTS</b>Compared with those in the control group, body weight, diaphragm to body weight ratio, Pt, Po, and tetanic force under the stimulus frequency of 10, 20, 40, 60, 100 Hz were all significantly decreased (P<0.01), while CT and 1/2RT were significantly prolonged in LC group (P<0.01). SOD and SDH activities were significantly lowered (P<0.01) while the contents of MDA and MPO activity were significantly increased in LC group (P<0.01) with significantly decreased SERCA, titin and nebulin mRNA expressions in the diaphragm (P<0.01). Electron microscopy of the diaphragm in LC group revealed myofibrillar degeneration, absence of the Z line, and mitochondria swelling and edema.</p><p><b>CONCLUSION</b>Liver cirrhosis increases free radicals and aggravates inflammatory response and lipid peroxidation in the diaphragm, thus leading to mitochondrial damages and decreased expressions of cytoskeletal proteins and SERCA to cause diaphragmatic dysfunction.</p>

Diaphragm dysfunction and expressions of calcium regulatory proteins in diabetic rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the changes in diaphragmatic function and gene expressions of calcium regulatory proteins in diabetic rats and explore the mechanism of diaphragm dysfunction in diabetes mellitus.</p><p><b>METHODS</b>SD rats were randomly divided into normal control group and diabetic (induced by intraperitoneal STZ injection) group. After 4 and 8 weeks, the body weight and diaphragm to body weight ratio were measured, and the activities of succinic dehydrogenase (SDH) in the diaphragm and blood glucose were assayed. The diaphragm contractility was assessed and the alterations of diaphragm ultrastructure were observed. RT-PCR was used to detect the changes in sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLB) mRNA expressions in the diaphragm.</p><p><b>RESULTS</b>The diabetic rats showed a significant weight loss with a lowered diaphragm to body weight ratio (P<0.01) and SDH activity (P<0.01). The peak twitch tension and maximum tetanic tension of the diaphragm were significantly lowered and the time to peak contraction and half relaxation time significantly prolonged (P<0.01) in the diabetic rats, which also exhibited a lowered tetanic force in response to stimulus (P<0.01). Transmission electron microscopy revealed obvious ultrastructural changes of the diaphragm in diabetic rats. RT-PCR showed significantly decreased SERCA and increased PLB mRNA expressions in diabetic rat diaphragm (P<0.01), and these changes intensified with time (P<0.01).</p><p><b>CONCLUSION</b>Diabetes can cause impairment of diaphragmatic ultrastructure, mitochondrial injuries, and lowered SDH activity and ATP production. Decreased SERCA and increased PLB mRNA expressions in diabetes result in reduced Ca(2+) uptake by the diaphragm sarcoplasmic reticulum to induce diaphragm dysfunction.</p>

Effect of soybean isoflavones on heart function of rats with adriamycin-induced heart failure / 中西医结合学报

OBJECTIVE: To observe the protective effect of soybean isoflavones (SI) on the heart function of the rats with adriamycin induced heart failure. METHODS: Thirty adult male SD rats were divided into 5 groups:normal control (NC) group, adriamycin (ADR) group, L-SI group, M-SI group and H-SI group. SI of 30, 60, 120 mg.kg(-1).d(-1) was orally administered through a stomach tube once a day for 6 days in L-SI group, M-SI group and H-SI group, respectively. The other two groups were given the same amount of normal saline the same way. Then ADR of 10 mg/kg was given intraperitoneally once to copy the model of heart-failure. The MedLab-U/4c biological signal collecting system was used to record and analyze the LVSP of the rats. The pathological changes of the cardiomyocytes were observed. RESULTS: As compared with NC group, the LVSP,+/-dp/dt max, Vpm of the ADR group were significantly lower (P<0.05 or P<0.01), but those of the H-SI group were markedly higher than those of the ADR group (P<0.01). Electron microscopic morphometry of the heart samples of the rats in ADR group revealed typical alterations, consisting an increase of collagen content, vacuolation, diminishing of the cardiomyocyte diameter, alteration of myofilaments and Z-lines of myofibers, and myofibrillar degeneration. SI of 120 mg.kg(-1).d(-1) treatment could prevent the loss of myofibrillae and the reduction of myocyte diameter, and the degeneration of myofilaments and Z-lines were reversed by SI. CONCLUSION: SI of 120 mg.kg(-1).d(-1) treatment can relieve the toxic effect of ADR on myocardium, and also obviously improve the cardiac contractility of heart-failure rats.

An Experimental Study on PBL Combined LBL Applied to Physiology Teaching / 中华医学教育探索杂志

An experimental study of two approaches of teaching——problem-based learning(PBL) combined with lecture-based learning(LBL) and LBL only——was conducted respectively in two classes of 2003 college students.It was proved that PBL combined with LBL has an obvious advantage over LBL only(P

Role of mitochondrial aldehyde dehydrogenase 2 in postconditioning induced cardioprotection / 中国药理学通报

Aim To investigate the role of mitochondrial aldehyde dehydrogenase 2 ( ALDH2) in the cardio-protection of ischemic postconditioning in isolated rat hearts. Methods Hearts isolated from male Sprague-Dawley rats were perfused on a langendorff apparatus and subjected to 30 min of regional ischemia( occlusion of left anterior descending artery) followed by 120 min reperfusion. Ischemic postconditioning was achieved by 6 cycles of 10 s reperfusion/10 s global ischemia starting at the beginning of reperfusion. The ventricular hemodynamic parameters and lactate dehydrogenase ( LDH) release during reperfusion were measured. The infarct size was measured by TTC staining method. The expressions of ALDH2,Bcl-2 and Bax at mRNA level of left anterior myocardium were detected by RT-PCR analysis. Results In contrast to ischemia and reperfusion,ischemic postconditioning improved the recovery of left ventricular developed pressure,rate pressure product during reperfusion,and reduced LDH release and infarct size. The expressions of ALDH2 mRNA level and the ratio of Bcl-2 /Bax were increased. Adminis-tration of ALDH2 antagonist cyanamide at the beginning of reperfusion attentuated the role of ischemic postconditioning. Conclusion Ischemic postconditioning plays a role in the cardioprotection partially through increasing mitochondrial ALDH2 mRNA expression.

Protective effect of taurine on diaphragm against adriamycin cytotoxicity / 中国药理学通报

AIM　To study protective effect of taurine on diaphragm against adriamycim cytotoxity in rabbits.METHODS　The rabbits were divided randomly into three groups.①Control group:The animals were administered NS 2 ml*kg-1 for five days. ②Adriamycin+NS group:The animals were administered NS 2ml*kg-1 for five days and then administered adriamycin 10 mg*kg-1.③Adriamycin+taurine group:The animals were administered taurine 100 mg*kg-1 for five days and then administered adriamycin 10 mg*kg-1.After 24 h,three groups animals were anaesthetized.The transdiaphragmatic pressure(Pdi) and diaphragm evoked potential(DEP) were measured.SOD and MDA were tested.the ultrastructure of diaphragm cells was investigated by eletronmicroscopy.RESULTS　The Pdi and amplitude of DEP were lowered by adriamycin(P＜0.01).The levels of MDA was increased and the activity of SOD was decreased in diaphragm(P＜0.05).The disorder of myofibrills,swelling of mitochondria with broken cristase can be observed by electronmicroscopy.The above changes were inhibited by taurine.CONCLUSIONS　The taurine could scavenge the toxic radicals generated by adriamycin and protect the diaphragm myocytes.

Protective Effect of Shengmai Injection on Adriamycin-induced Cytotoxicity of Diaphragm / 中药新药与临床药理

To study the protective effect of Shengmai Injection on adriamycin-induced cytotoxity of diaphragm in rabbits. The rabbits were randomly allocated to three groups. The control group were treated with NS 2 ml?kg -1 for five days, adriamycin+NS group with NS 2ml?kg -1 for five days and then administered adriamycin 10 mg?kg -l and adriamycin + Shengmai Injection group with Shengmi Injection 2 ml?kg -l for five days and then administered adriamycin 10 mg?kg -1 . Twenty-four hours later, animals in the three groups were anaesthetized. Then the transdiaphragmatic pressure (Pdi) and diaphragm evoked potential(DEP) were measured, SOD activity and MDA content were tested and the ultrastructure of diaphragm cells was observed under electron microscope. Adriamycin could lower the Pdi and amplitude of DEP (P

Protective Effect of Taurine on Diaphragm in Diabetic Rats / 广州中医药大学学报

[Objective] To observe protective effect of taurine, a main component of Calculus Bovis and Scorpio, on diaphragm in diabetic rats. [Methods] Twenty-four SD rats were equally randomized into normal control group, model group and taurine group. Except the normal control group, the other rats were given intraperitoneal injection of streptozotocin 50mg/kg to induce diabetic models. Taurine group was fed with 10g/L water solution of taurine, and the other two groups with water for 4 weeks. After treatment, the rats were executed and the isolated diaphragm strips were prepared. Single contraction (SC) , maximum titanic tension, contraction time, half relaxation time, force-frequency curve and fatigue index (FI) of the diaphragm strips were examined. The contents of blood sugar, superoxide dismustase (SOD) and malondialdehyde (MDA) in the diaphragm were detected and the diaphragm ultrastructure was also observed. [Results] SC, maximum titanic tension and fatigue index were decreased, contraction time and half relaxation time prolonged, diaphragm tension in force-frequency curve decreased, SOD activity reduced and MDA content increased in the model group (P

Effects of Soy Isoflavones on NO Content and NOS Activity in Myocardial Tissues of Diabetic Rats / 中药新药与临床药理

Objective To observe the effects of soy isoflavones (SI) on NO content and NOS activity in myocardial tissues of diabetic rats. Methods Forty-eight SD rats were randomly divided into six groups: normal control group (NC), diabetic control group (DC), SI groups in low, moderate and high doses respectively (L-SI, M-SI, H-SI) and nilestriol group (NI). Except the NC group, the rats were given streptozotocin (STZ) 55mg?kg-1 intraperitneally (ip). From the 7th week, SI in the dosage of 30, 60, 120 mg?kg-1?d-1 was respectively given to L-SI, M-SI, H-SI groups by gastric gavage, nilestriol 0.2 mg?kg-1?per week was given to NI group,and 0.5%CMC-Na10 ml?kg-1?d-1 was given to NC and DC groups. After treatment, fasting blood sugar level, body weight, serum lactate dehydrogenase (LDH)and creatine kinase (CK) contents, and NOS activities and NO content in myocardial homogenate were measured. Results 1) LDH and CK contents in serum were significantly higher in DC group than those in NC group. Compared with DC group, LDH and CK were significantly decreased in M-SI and H-SI groups (P

Effects of the Combination of Shenmai Injection and Aminophylline on Diaphragmatic Function in Rabbits / 中药新药与临床药理

Objective: Effects of Shenmai injection and aminophylline alone or in combination on transdiaphragmatic pressure and electrical activity of diaphragm were observed, so as to evaluate their effecfs on diaphragmatic fatigue. Methods: The diaphramatic fatique (DiF) model was estab- lished by stimulating bilateral phrenic nerves for 40 minutes. The animals were allocated to three groups: Shenmai group (2mL/kg, N=7), aminophylline group (20mg/kg, N=7) and combi- nation group (Shenmai injection 2mL/kg+aminophylline 20mg/kg, N=7) The transdi- aphragmatic pressure (Pdi) and diaphragmatic electromyogram (EMGdi) were recorded before and after treatment. EMGdi was analysed by computer and then the high/low frequency ratio (H/L) and the central frequency (Fc) were caculated. The diaphragm evoked potential (DEP) was record- ed simutaneously. All data was analysed by analysis of variance and q test. Results: Pdi, H/L, Fc and amplitude of DEP were markedly increased after the treatment with aminophyline and Shen- mai injection alone (Compared with DiF. P

Protective effect of taurine on diaphragm against adriamycin cytotoxicity / 中国药理学通报

AIM To study protective effect of taurine on diaphragm against adriamycim cytotoxity in rabbits. METHODS The rabbits were divided randomly into three groups. groups group: The animals were administered NS 2 ml.kg- 1 for five days. ②Adriamycin + NS group: The animals were administered NS 2ml. kg-1 for five days and then administered adriamycin 10 mg. kg- 1. ③Adriamycin + taurine group: The animals were administered taurine 100 mg. kg-1 for five days and then administered adriamycin 10 mg?kg- 1. After 24 h, three groups animals were anaesthetized. The transdiaphragmatic pressure(Pdi) and diaphragm evoked potential(DEP) were measured. an and MDA were tested. the ultrastructure of diaphragm cells was investigated by eletronmicroscopy. RESULTS The Pdi and amplitude of DEP were lowered by adriamrcin(P

Effects of neostigmine on the transdiaphragmatic pressure and diaphragm evoked potential in rabbit / 中国药理学通报

Experiments were performed on spontaneously breathing rabbits anesthetized with urethan. The diaphragmatic fatigue (DiF) was reproduced by the phrenic nerve stimulation (30 Hz, 10 V,0. 2 ms). The transdiaphragmatic pressure (Pdi) and diaphragm evoked potential (DEP) were measured before injury and after injury 30, 60, 90, and 120 min. Pdimax and the amplitude of DEP obviously decreased and the latency of DEP obviously delayed after injury 30min. The amplitude of Pdi and DEP were quickly promoted by introvenous injection of neostig-mine after DiF. The latency of DEP was partially recovered by introvenous injection of neostig-mine. It is concluded that neostigmine can improve the generation of the fatigued diaphragm. and promote its recovery.