| Objective:To observe the effects of Lingguizhugan decoction and Tinglidazao Xiefei decoction on preventing and treating ventricular remodeling of CHF rats induced by Adriamycin.Some indexes of Ang II-NADPH oxidase-Ros signaling pathway and Expression of p47 phox in myocardium were used to illustrate the effective mechanism of the treatment of Warming Yang for resolving fluid in preventing and treating ventricular remodeling of CHF.Methods:Wistar rats were randomly divided into blank contro Group L(Group K)and group A.The model of ventricular remodeling induced by chronic congestive heart failure(CHF)was established by intraperitoneal injection of Adriamycin.After the modeling,group A rats were randomly divided into mode Group L(Group M),Warming Yang for resolving fluid group(Group Y),Warming Yang for resolving fluid without Guizhi group(Group Q)and Warming Yang for resolving fluid without Guizhi and Fuling group(Group L).Group Y was given Warming Yang for resolving fluid decoction at the equivalent dose of 12g/kg·d once a day for 4 weeks by gavage;Group Q was given Warming Yang for resolving fluid decoction without Guizhi at the equivalent dose of 10g/kg·d once a day for 4 weeks by gavage;Group Q was given Warming Yang for resolving fluid decoction without Guizhi and Fuling at the equivalent dose of 6.6g/kg·d once a day for 4 weeks by gavage;Group M was fed with distilled water of equal volume based on Group Y,and Group K was fed under the same conditions without any administration plan.The general condition of rats was observed during the experiment.After the experiment,ultrasonic cardiogram and urine volume were measured,and the morphologic changes of ventricular tissue were observed.The levels of angiotensin Ⅱ,renin and aldosterone in serum were detected.Angiotensin Ⅱ,hydroxyproline(HYP),reactive oxygen species(Ros),malondialdehyde(MDA),superoxide dismutase(SOD)and NADPH oxidase 2(NOX2)in left ventricular myocardium were detected.The m RNA of P47 phox was detected by PCR and p47 phox protein was detected by western-blot.Results:1.Cardiac function:(1)IVSd: Compared with the Group K,the Group M was significantly thickened(p<0.05),and compared with the Group M,the Group Y was obviously thinner(p<0.05),but there was no significant difference between the Group Q and the Group L as compared with the Group M(p>0.05);(2)LVIDd: Compared with Group K,Group M decreased significantly(p<0.05),and Group Y increased significantly compared with Group M(p<0.05),and there was no significant difference between Group Q and Group L(p>0.05);(3)LVPWd: Compared with Group K,Group M was thicker(p<0.05),and Group Q was thinner than Group M(p<0.05),Group Y and Group L had the tendency of thinning,but the difference was not significant(p>0.05);(4)EDV: Compared with Group K,Group M decreased significantly(p<0.05),and Group Y and Group L increased significantly compared with Group M(p<0.05),Group Q had an increasing trend but the difference was not significant(p>0.05);(5)SV:Compared with Group K,Group M was significantly lower than Group K(p<0.05),Compared with Group M,Group Y,Group Q and Group L were significantly increased(p<0.05),There was no significant difference between Group Y 、Group Q and Group L(p>0.05);(6)EF:Compared with Group K,rats in Group M were significantly lower than those in Group K(p<0.05);Compared with Group M,Group Y,Group Q and Group L were significantly increased(p<0.05);There was no significant difference between Group Y,Group Q and Group L(p>0.05).(7)HR:Compared with Group K,Group M increased significantly(p<0.05);Compared with Group M,Group Y decreased significantly(p<0.05),there was no significant change in Group Qand L group(p>0.05),compared with the Group Y,the Group Q and Group L significantly increased(p<0.05);(8)CO:Compared with the Group K,the Group M was significantly reduced(p<0.05),compared with Group M,Group Y,Group Q and Group L were significantly higher than those in Group M(p<0.05);There was no significant difference between Group Y,Group Q and Group L(p>0.05).2.Ventricular remodeling index:(1)HYP:Compared with Group K,Group M increased significantly(p<0.05),Compared with Group M,Group Y,Group Q and Group L decreased significantly(p<0.05),there was no significant difference between Group Yand Q group(p>0.05),Group L was significantly higher than Group Y and Group Q(p<0.05);(2)CVF:Compared with Group K,Group M increased significantly(p<0.05),compared with Group M,Group Y and Group Q decreased significantly(p<0.05),there was no significant difference between Group Y and Group Q(p>0.05),there was no significant change in Group L as compared with Group M(p>0.05).3.Related indexes of renin-angiotensin-aldosterone system:(1)serum ALD:Compared with the K group,the Group M was significantly reduced(p<0.05),there was no significant difference in Group Q and Group Y compared with Group M(p>0.05)while significant decreased in Group L.(2)serum AngⅡ:Compared with Group K,Group M increased significantly(p<0.05),Compared with Group M,Group Y and Group L were significantly lower than those of Group M(p<0.05),and the decrease of Group Q was not significant(p>0.05).(3)serum Renin:Compared with Group K,Group M increased significantly(p<0.05),compared with Group M,Group Y,Group Q and Group L decreased significantly(p<0.05).(4)AngⅡ in left ventricular myocardium:compared with Group K,Group M increased significantly(p<0.05),compared with Group M,Group Y,Group Q and Group L decreased significantly(p<0.05),there was no significant difference between Group Y,Group Q and Group L.4.Related indexes of oxidative stress:(1)SOD: Compared with Group K,Group M decreased significantly(p<0.05),compared with Group M,Group Y,Group Qand Group Lwere significantly higher(p<0.05),there was no significant difference between Group Y,Group Q and Group L(p>0.05).(2)ROS: Compared with Group K,Group M increased significantly(p<0.05),Compared with the Group M,the Group Qand Group Y were significantly lower than that in the Group M(p<0.05)while not changed in Group L(p>0.05),compared with Group Y,Group Q and Group L were significantly higher than Group Y(p<0.05),compared with Group Q,Group L increased significantly(p<0.05).(3)MDA: compared with Group K,Group M increased significantly(p<0.05),compared with Group M,Group Y,Group Q and Group L decreased significantly(p<0.05),there was no significant difference between Group Q and Group Y(p>0.05)while Group L increased compared with Group Y(p<0.05).(4)NOX2: compared with Group K,Group M increased significantly(p<0.05),compared with Group M,Group Y and Group Q decreased significantly(p<0.05)while not in Group L(p>0.05).(5)p47phoxm RNA: compared with Group K,Group M increased significantly(p<0.05),compared with Group M,Group Y decreased significantly(p<0.05)while not in Group Q and Group L(p>0.05).(6)P47phoxprotein quantity: compared with Group K,Group M increased significantly(p<0.05),compared with Group M,L group,Group Q and Group L decreased significantly(p<0.05).Conclusion:1.Adriamycin intraperitoneal injection can successfully replicate CHF rat model and cause cardiac dysfunction and pathological changes of left ventricular remodeling characterized by left ventricular diastolic dysfunction;2.The treatment of Warming Yang for resolving fluid could significantly improve cardiac function.The mechanism relates to regulation of Ang II-NADPH oxidase Ros signaling pathway.The treatment of Warming Yang could regulate serum RAAS system and myocardial Ang II,oxidative stress system and the expression of myocardial p47 phox,which are the possible mechanisms of its prevention and treatment of ventricular remodeling in CHF rats;3.In the treatment of Warming Yang for resolving fluid,warming Yang medicine(Guizhi)could reduce heart rate and improve CO which plays a role in improve positive inotropism;4.The treatment of Warming Yang for resolving fluid is an effective treatment for phlegm and fluid disease.In this experiment,the key to its effect is to promote the Qi transformation of the body,rather than the effect of pure hydrophilic drugs.It is suggested that the term " Warming Yang for resolving fluid " should be used in summing up the basic treatment of phlegm and fluid disease,which is to reflect and emphasize the effect of the treatment by promoting the Qi transformation of the body. |
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