| ObjectiveCardiovascular disease is the major cause of morbidity and mortality in patients with diabetes mellitus.Although our country put a lot of manpower and material resources to diabetes mellitus,its incidence and mortality remains at high risk because of the complexity of pathogenesis.Thus prevention of diabetes has become the focus of public and the medical community of common concern.Long-term diabetes mellitus accompanies autonomic nervous system dysfunction inducing cardiovascular disease,and cause serious damage to the heart,brain,kidneys and other vital target organs.Physcion belong to anthraquinones,mainly in rhubarb and giant knotweed polygonum plants and other roots and rhizomes.Physcion have anti-inflammatory,antioxidant and anti-apoptosis effect.Firstly,in order to explorer the effect of physcion on blood pressure and cardiac endocrine function,the experiments were performed in normal rabbit.Secondly,diabetes mellitus rat model was established,and the intervention effects of the physcion to diabetes mellitus rats were observed through detection of myocardial morphology,diabetes mellitus related parameters and the changes in the levels of plasma active components.Moreover,it was also investigated whether physcion could improve cardiac endocrine function.The study suggested that physcion has protective effect on cardiac function in physiological and diabetes mellitus conditions.Methods(1)Animals were anesthetized by an intra-peritoneal injection of 20%urethane(1g/kg).Carotid artery and femoral vein were cannulated for continuous blood pressure monitoring and different doses of physcion administration.A BL-420s physiological signal system was used to record the arterial blood pressure.(2)Effects of physcion on atrial dynamic and ANP secretion:In order to investigate the effects and mechanism of physcion on changes in atrial dynamics and ANP releas,isolated perfused atria beating experimental model and radioimmunoassay technique were used in this study.Experiments were performed on anesthetized rabbits and rats.Isolated left atrium fixed to the experimental model.The atrium was perfused with HEPES buffer for 60 min to stabilize ANP secretion and atrial dynamics.[~3H]Inulin was introduced to the pericardialfluid 20 min before the start of sample collection.The perfusate was collected(42 sample)for ANP analysis at 2-min intervals at 4℃.In order to observe the effects of physcion on atrial dynamic and ANPsecretion,an initial control period of 48 min was followed by physcion infusion for 36 min.Nifedipine(nife),a L-type calcium channel blocker,was used to investigate the mechanisms of physcion increase in atrial dynamic and ANP release.(3)Establish DM rat model:DM rats were induced by a single intraperitoneal injection of streptozotocin(STZ)at a dosage of 50 mg/kg body weight after feeding high fat diet for 45 days.The plasma glucose levels of rats were measured 3 days after injection.The diabetic DM rats chosen for the study had plasma glucose of 16.7 mmol/L or higher.(4)Physcion intervention and experimental groups:DM selected successful model rats begin to DM rats fed physcion(30 mg/kg/d)and maintained for 4 weeks,were physcion intervention.They were divided into 3 groups,including control group,DM group,physcion(30 mg/kg/d)DM group physcion.(5)Physcion improved cardiac function in rats with experimental DM:The physcion intervention,the myocardial tissue embedded in paraffin,using HE staining and masson staining cardiac cell morphology and myocardial collagen fibers;detecting DM Related indicators such as blood glucose,body weight,atrial weight/body weight changes,water intake and systolic blood pressure;detection of plasma and myocardial tissue of cardiovascular active ingredient,nitrate reductase assay NO levels to radioimmunoassay ANP,angiotensin II(Ang II)and endothelin-1(ET-1)levels;the use of in vitro experimental model of atrial perfusion and radioimmunoassay techniques discussed physcion improved acetylcholine(ACh)to promote Attenuation of atrial ANP secretion.Results(1)Physcion a concentration-dependent decrease in systolic blood pressure in normal rabbits.0.5 mg/kg after intravenous injection physcion systolic blood from 113.56±5.89mmHg decreased to 80.14±0.78 mmHg.Different doses physcion(0.1,0.5,1 mg/kg)Inhibition percentage of systolic blood pressure were 18.56±1.55%,27.31±1.09%and38.65±1.89%,there were significant differences.(2)Meanwhile physcion promote atrial ANP secretion inhibition rabbits atrial power(including atrial volume and cardiac output per Bo room pressure).Rabbits atrial ANP secretion from the control group 13.25±3.22 ng/min/g increased to 29.56±4.59ng/min/g,ANP content in the control group by 0.36±0.09μM increased to 0.72±0.05μM;concentration 30μM of physcion rabbits can reduce stroke volume and stroke pressure:stroke volume rabbits from the control group 482.39±5.99μl/g reduced to 380.52±7.19μl/g,significant difference(P<0.05);and rabbit stroke pressure decreased from7.89±0.12cmH2O reduced to 4.95±0.09 cmH2O,with a significant difference(P<0.05).And showed a concentration-dependent change physcion Rabbits ANP secretion and atrial power.Pretreatment nifedipine significantly increased physcion change induced atrial ANP secretion and atrial kinetic parameters.(3)After gavage with Physcion myocardial morphology DM,DM-related indicators,systolic blood pressure and plasma levels of the active ingredient tends to normal.Blood glucose control rats was 6.38±0.14 mMol/L,glucose DM rats after STZ injection was significantly increased compared with Sham group,the difference was significant(P<0.001 compared to 27.63±1.27mMol/L,and the control group),while physcion DM rats fed sugar declined in the late statistically significant(P<0.01)compared to a difference of 20.80±0.93 mMol/L,with the control group,compared with DM group there was significant difference(P<0.05).Weight After model DM rats was 351.30±18.33 g,compared with the control group 522.87±35.16g significantly lower compared with the control group do not have a significant difference(P<0.01).Effect physcion DM rats fed on body weight were increased compared with DM group,DM physcion fed rats weighing442.19±18.75 g,and diabetes was significantly increased compared to body weight,there was a significant difference(P<0.05).Atrial DM rats weight/body weight ratio compared with the control group 0.09±0.02mg/g increased significantly as 0.04±0.01 mg/g,there was a significant(P<0.001)compared to the difference between the control group and emodin armor atrial ether gavage DM rats weight/body weight ratio was 0.057±0.01 mg/g,the atrium and DM rats compared weight/body weight ratio was significantly reduced,with significant differences(P<0.01).The amount of water DM rats than in the control group was 59.5±6.82ml significantly higher 88.33±3.09 ml,there was a significant(P<0.01)differences compared with the control group,physcion oral DM rats water intake was50.83±2.62 ml,the amount of water compared with DM rats significantly reduced,with significant differences(P<0.001).During the experiment,the control rats blood pressure was stable,the systolic blood pressure was 101.95±2.63 mmHg,systolic DM rats was of139.35±8.46 mmHg,a significant increase compared with the control group,with significant difference(P<0.05).The oral Physcion SBP DM group was109.73±6.74 mmHg,compared with DM group decreased significantly,the difference was significant(P<0.05).The oral physcion SBP DM group was 109.73±6.74 mmHg,compared with DM group decreased significantly,the difference was significant(P<0.05).The levels of ANP,NO,AngII and ET-1 in DM group plasma were obviously higher than the control group(P<0.01).The levels of ANP and NO in DM group atrium were significantly lower than the control group(P<0.05),while the levels of Ang II and ET-1 were obviously higher than the control group(P<0.01).The levels of ANP,AngII and ET-1 in DM group ventricle were obviously higher than the control group(P<0.05),while the levelof NO significantly lower than the control group(P<0.05).After gavage withphyscion,the levels of ANP,NO,AngII and ET-1 in DM group plasma,atrium,ventricle was back to the normal levels.(4)DM under pathological conditions,ACh promote atrial ANP secretion and the inhibitory effect of atrial power weakened,and is able to improve this physcion weakening effect.In DM group,the secretion of atrial ANP percentage promoted by ACh(0.1μM)was 16.14±4.58%,compared with the control(42.9±7.82%)significantly decreased,with sign-ificant differences(P<0.001).While the physcion DM group was40.52±5.62%,compared with control group,with no statistical difference(P>0.05).In DM group,the secretion of atrial ANP percentage inhibited by ACh(0.1μM)was-26.15±3.09%,compared with the control group(-52.80±6.82%)significantly decreased(P<0.001).While the physcion DM group was-49.10±2.62%,compared with control group,with no statistical difference(P>0.05).Conclusions(1)In physiological conditions,physcion can reduce systolic blood pressure,and the effect closely related to the increases the secretion of atrial ANP secretion;physcion accentuate atrial ANP secretion through inhibition of L-type calcium channels,further exerts its cardiac protective effect.(2)Physcion can reverse diabetes mellitus related parameters and the changes in the acetylcholine regulation of atrial ANP secretion.Physcion ether can obviously improve the related parameters of DM rats,and reversible the inhibitory effect of parasympathetic neurotransmitter ACh promoting atrial ANP secretion.This study suggests physcion in the physiological/DM pathological state play a role of the protection of cardiac function by promoting effect of atrial ANP secretion. |
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