The Study On Pharmacodynamics And Material Basis Of The Combination Of Corni Frucrus And Chinese Yam On Diabetic Cardiomyopathy

Cornus officinalis Sieb.et Zucc,(Cornaceae),a dried ripe red brown fruit,often appeared in traditional Chinese medicine formulations,such as liu-wei-di-huang pills,for the treatment of diabetes.Numerous medical books had recorded it can tonfy the liver and kidney,solidify collapse.Clinical indications include to swimmy tinnitus,lumbar genu ache,impotence spermatorrhea,enuresis frequent micturition,and metrorrhagia and metrostaxis,heat dissipation of thirsty.It had been reported that morroniside was a major active component of Cornus officinalis and had a markedly anti-diabetic effect via reducing oxidative stress,inflammation,and apoptosis.Dioscorea opposita Thunb,(Dioscoreaceae),known as "Shanyao" in Chinese,is used as herb pairs of Cornus officinals in the prescriptions of traditional C hinese medicine dictionary for the treatment of diabetes and can reinforce the liver,kidney,spleen and gastric.Literature has reported that diosgenin was major a steroidal saponin in yam and the main metabolite of the steroidal saponins in vivo.In addition,diosgenin has potential effects on cardiovascular diseases and diabetes.Therefore,the aims of the present study were to investigate myocardial protective effect of combination of Morroniside and Diosgenin on diabetic cardiomyopathy(DCM).There are three parts in this thesis.The first part,the aims is to investigate myocardial protective e ffect of combination of Corni Frucrus and Dioscorea opposita crude extract.First,experimental diabetic model was induced by intraperitoneally injection of streptozotocin.Those mice with blood sugar>16.7mmol/L were regarded as Diabetic mice.Then,body weight,water intake,food intake,heart weight/body weight and blood sugar were measured during the experiment.Finally,after the experiment,the Serum insulin,MDA of myocardial tissue and pathological sections of myocardial tissue(HE staining,immunohistochemistry)were determined.The result showed high dose group could significantly reduce blood glucose in mice,enhance SOD activity and MDA levels in myocardium,promote insulin secretion and decrease the expression of TGF-β1 in myocardium.Conclusion:The Combination of crude extracts of Cornus officinalis and yam has protective effect on diabetic mice’s myocardium.The second part,the aims is to establish a model of myocardial injury induced by high glucose and investigate the myocardial protective effect of combination of Morroniside and Diosgenin.We detected cell viability,cell apoptosis,intracellular reactive oxygen species(ROS)levels,and the expression levels of Bcl-2,Bax,and caspase-3 protein in rat cardiomyocytes.In result,Mor,Dio,and M+D increased cell viability,inhibited cell apoptosis and decreased ROS levels.Additionally,the expression of Bax and Bcl-2 protein was modulated and the expression levels of caspase-3 protein were markedly decreased.Among the treatment groups,M+D produced the most prominent effects.In conclusion,our data showed for the first time that Mor,Dio,and M+D prevented high glucose(HG)-induced myocardial injury by reducing oxidative stress and apoptosis in rat cardiomyocytes.Among all the groups,M+D produced the strongest effect,while Mor and Dio produced weaker effects.The third part,the aims is to enrich and purify iridoid glycoside effective parts and make fingerprints.First,we can get crude extracts by using macroporous resin to purify and enrich the effective components of Corni Frucrus.Then,furthermore purify by using petroleum ether,ethyl acetate,n-butanol extract.The final the content of part is greater than 50%.Finally,we make the fingerprints of iridoid glycoside effective fraction.The stability of the preparation method was investigated,which can as a quality control and application of the reference from part of cornel iridoid glycoside.