A Experiment And Clinical Research On The Ventricular Remodeling Of Chronic Heart Failure Treating By Dan Qi Bdo Xin Fang

Study background:Ventricular remodeling is pathophysiologic foundation of chronic heart failure (CHF), while CHF could worsen ventricular remodeling, finally results in vicious circle. Modern studies show that deficiency of qi an d yin, turbid phlegm, static blood, and water retention are the possible pathoge ns and pathogenesis of ventricular remodeling. The study is going to reveal the effect and mechanism of TCM in treating ventricular remodeling of CHF by r esearching hospital preparation named, which consists of huang qi, dan shen, mai dong, fu ling, ze lan, and shui zhi.Objectives:To explore therapeutic effect of dan qi bao xin fang in treati ng CHF by experimental and clinical research, and its possible molecular mech anism in improving ventricular remodeling.Methods:1.Animal experiment100SD rats were divided into model group and control group. CHF rat model was induced by intraperitoneal injection with Adriamycin, and evaluated by echocardiography and histopathological detection8weeks later. After CHF was induced successfully, they are randomly divided into dan qi bao xin fang high-dose, medial-dose, and low-dose group, positive group and vehicle group. They were administrated by gavage with high-dose, medial-dose, and low-dose dan qi bao xin fang (medial-dose is the clinical equivalent dose), enalapril for positive group, and water for vehicle and control group for4weeks. The gen eral conditions were observed, heart structure and function were evaluated by t wo-dimensional echocardiography, histologic examination for heart and lungs, B NP, MMP-1, and MMP-9of blood serum were tested by ELISA; the mRNA t ranscriptional level of MMP-9, TIMP-1, and JNP in myocardial tissue were tes ted by RT-PCR, and expression of JP-2in myocardial tissue was tested by im munohistochemistry and Western blot. 2.Clinical experiment65CHF patients were divided into control group with32cases and experi mental group with33cases. The control group were given western basic treat ment, and experimental group were given western basic treatment with prepare d powder of dan qi bdo xin fang for4weeks. The general information, such as age, gender, and accompanying diseases were observed, carotid plaque were detected with vascular color doppler ultrasound and integrated, changes of NH YA cardiac function, clinical symptoms integral, and Minnesota heart failure lif e quality score before and after the treatment were observed.Results:1. CHF rats model were successfully induced by intraperitoneal injection with Adriamycin1.5mg/kg/d for6weeks.2. Pathological changes of myocardial and pulmonary tissues2weeks after inducing CHF model, some myocardial cells manifested as edema and vacuolar degeneration, some as steatosis, or small focal necrosis; so me myofibrils dissolved, myocardial fiber broken; myocardial cell space was wi dened and infiltrated by inflammatory cells. The lung suffered from alveolar bl eeding, some alveolar effusion, pulmonary interstitial edema and congestion, an d inflammatory cell infiltration. After gavage for4weeks, the above pathologic al changed of high-dose and medial-dose group were improved.3. Two-dimensional echocardiography2weeks after inducing CHF model, LVIDs and LVIDd were higher than control group (P<0.05), and EF and FS lower (P<0.05);4weeks after gavage with dan qi bdo xin fang, LVIDs, LVIDd, EF and FS were recovered to accor dance with control group; LVIDs and LVIDd were lower than vehicle group (P<0.05); and EF higher (P<0.05).4.Changes of MMP-1、MMP-9in blood serumMMP-1and MMP-9of vehicle group were higher than control group and groups treated by dan qi bdo xin fang (P<0.05).5.mRNA expression of MMP-9, TIMP-1and JNK in myocardial tissuesmRNA expression of MMP-9and JNK of vehicle group was higher than control group, while that of TIMP-1lower (P<0.05). The mRNA expression of MMP-9and JNK of high-dose and medial-dose group were lower than vehicl e and low-dose group, and that of TIMP-1higher (P<0.05).6.Expression of JP-2in myocardial tissuesCompared with control group, the expression of JP-2of vehicle group wer e decreased (P<0.05). Compared with vehicle group, that of positive group, an d high-dose group were increased (P<0.05), and that of medial-dose and low-d ose tended to increase.7. Carotid artery plaque integralCarotid plaque integral of level Ⅲ NHYA cardiac function was significant1y higher than level Ⅱ (P<0.01).8. TCM clinical symptoms integralThere was obvious difference of experimental groups before and after the treatment (P<0.05).9. Minnesota heart failure life quality scoreThere was obvious difference of experimental groups before and after the treatment (P<0.05). Compared with control group, the experimental groups were better than control group (P<0.05).10. Statistics on cardiac function effectThe overall response rate (ORR) of experimental groups were96.7%, whil e that of control group was76.6%, which indicated obvious difference (P<0.05).Conclusions:The study shown that dan qi bao xin fang is effective in tre ating CHF model rats by inhibiting myocardial apoptosis and improving ventric ular remodeling. Meanwhile, dan qi bao xin fang is effective for CHF patients by manifesting as improving the clinical symptoms and life quality.