Chronic Heart Failure Rat Myocardial MMP-9, TIMP-1 Expressed And The Effects Of Tinglishengmaifang

Objective: Tinglishengmaifang(It was composed of hongshen, shenghuangqi, danshen, honghua, chishao, tinglizi, yimucao, maidong and wuweizi) have efficacy of yiqi, huoxue,lishui. Throug clinical observation, the treatment of chronic heart failure have a better effect. In order to further explore the mechanism, according to reference documents,CHF model was established by constriction of abdominal aorta, at the same time,the animal was interfered with medicine,to observe Cardiac function, morphology of myocardial tissue, Serum inflammatory cytokines and the expression MMP-9,TIMP-1 in chronic heart failure rat myocardial,to further explore Tinglishengmaifang in the treatment of chronic heart failure.Method:PartⅠEffect of Tinglishengmaifang on cardiac function in rats with chronic heart failure1 Animal grouping60 healthy adult Wistar rats,the female and the male were equal,weight from 160g to 180g,divided into 5 groups at randomly:sham operated group;model group;high-dose group;low-dose group;xinbao group.Every group were 12.2 Set up modelAfter feed one week model group,high-dose group,low-dose group,xinbao group were established by suprarenal aortic constriction opratde, in order to set up chronic heart failure mode.Sham-operated group only thread through the ab-dominal aorta after abdominal surgical,not ligation.3 Give experimental drugHebei Medical University College of Traditional Chin-ese Medicine Traditional Chinese Medicine to provide Tin-glishengmaifang (tinglizi hongshen maidong wuweizii and so on).Xinbaowan(20 / bottle, Lot: 20070631). Shantou City Kirin Pharmaceutical Co., Ltd. Product To give drug after set up model eight weeks,high-dose group,low-dose group given the Tinglishengmaifang orally separately by 30g/kg,15g/kg(chinse medicine drug),xinbao group give 0.24/kg(xinbaowan drug).Sham operation group and model group were given normal saline,1/d,consecutive eight weeks.4 Detect indicatorsAftre eight weeks, 20% urethane (1g/kg) by intraperitoneal injection of anesthesia,insert a cardiac catheterization by right carotid artery to left ventricular,use MS-4000U biological signal collecting system to record and analyze LVSP,LVEDP,±dp/dtmax,, detection heart function;cut little myocardial tissue,and fixed them in formaldehyde,then sliced up,dyed by HE methods,to observe the change of pathomorphism of cardiac muscle under microscope; check arterial blood,separate serum, examine the contents of TNF-αand IL-6 by radiation immunization method. ParⅡChronic heart failure rat myocardial MMP-9,TIMP-1expressed and the Effects of Tinglishengmaifang The group distribution an drug-given were the same asabove. After 12 weeks, the rats were forbidden to eat for12h, Animal anesthesia, cut little myocardial tissue, and fixed them in formaldehyde,then sliced up use immunohistochemical method to detection in rat myocardial tissue MMP-9,TIMP-1expression, use Motic 6.0 digital image analysis system to determin integral optical density value,semi-quantitative analysis of MMP-9, TIMP-1 expression. Dyed by M-asson methods,to observe the Changes in myocardial collagen,use Motic 6.0 digital image analysis system analysis myocardial collagen volume fraction (CVF).Statistical methodsSPSS12.0 statistical software used to statistical and analysis, all date are expressed by x±s, there was significantly when p<0.05.Results:PartⅠEffect of Tinglishengmaifang on cardiac function in rats with chronic heart failure1 Chronic heart failure rat heart function changesCompared with the sham operated group (LVSP:144.46±3.2;±dp/dtmax:11071.16±220.92, 7597.79±55.040;LVEDP:1.7±0.98) chronic heart failure rats LVSP(109.46±2.14) and ±dp/dtmax (5659.22±143.90,3141.07±37.31)to reduce,LVEDP (12.8±3.45)to increased, there is significant difference (P<0.01).2 The effects of tinglishengmaifang on heart function of ra ts with a chronic heart failureCompared with the mode operated group(LVSP:109.46±2.14;±dp/dtmax:5659.22±143.90,3141.07±37.31;LVEDP:12.8±3.45), high-dose group and low-dose group LVSP(139.92±2.25,123.32±3.35),±dp/dtmax (8519.13±144.76,6083.96±22.63;7340.54±65.85,4620.63±25.05) increased; LVEDP (2.0±0.58,2.0±0.9) weakened,there is significant difference(P<0.01orP<0.05);high-dose group is better than low-dose group,there is significant difference (P<0.05orP<0.01). 3 The effects of tinglishengmaifang on cardiac pathological histology of rats with a chronic heart failureUnder the microscope can be seen model group myocardial cells with disordered,compared with sham operated group hypertrophy,cell spacing edema widened,cell nucleus myocardial Compared with the mode operated group high-dose group and low-dose group,myocardial cells were arranged regularly,edema markedly improved;masson staining, myocardial collagen expression reduced significantly,CVF decresed,there is significantly difference(P<0.05orP<0.01), mesenchymal cell proliferation,markedly increased myocardial fibers,thickening,with disorder,a few inflammation cells and disruption could be seen. 4 The effects of tinglishengmaifang on content of TNF-αand IL-6 of rats with chronic heart failureCompared with shampgroup (TNF-α:0.649±0.034,IL-6:95.385±2.092) mode group the TNF-α(1.26±0.05) and IL-6 (193.43±4.8)increased(P<0.01),high-dose group and low-dose group TNF-α(0.76±0.03,0.94±0.13) and IL-6 (193.43±4.83,128.85±2.075) weakened, there is significant difference (P<0.05orP<0.01), compared with the xinbao group (0.98±0.05,166.87±4.88),high-dose group is better,there is significant difference (P<0.05orP<0.01),low-dose group and xinbao group showed no significant difference(P>0.05).ParⅡChronic heart failure rat myocardial MMP-9,TIMP-1expressed and the Effects of TinglishengmaifangThe effects of tinglishengmaifang on cardiac MMP-9 ,TIMP-1 and CVF of rats with chronic heart failureCompared with the mode group (MMP-9:0.187±0.011,TIMP-1:0.072±0.005:MMP-9/TIMP-1:2.026±0.100,CVF:18.61±0.87),high-dose group and low-dose group MMP-9 (0.096±0.007,0.133±0.007) weakened,TlMP-1(0.136±0.003,0.113±0.004) improved, MMP-9/TIMP-1(0.915±0.221,1.196±0.079)weakened , CVF(9.26±0.60,12.90±0.73)weakened ,there is significant difference(P<0.05orP<0.01);compared with the xinbao (0.136±0.112,0.116±0.008,13.10±0.82) group,high-dose group is better,there is significant difference (P<0.05 or P<0.01),low-dose group and xinbao group showed no significant difference(P>0.05). Conclusion:1 Rat myocardial tissue MMP-9, TIMP-1 expression, TNF-α, IL-6 over-expression,common cause ventricular remodeling, Cause myocardial cells and extracellular matrix patterns, the increase in the number, Reduced myocardial contractility and compliance. Cause chronic heart failure in rats2 Tilishengmaifang with yiqi,huoxue,lishui role, can inhibit the expression of MMP-9 and inflammatory factor,incrise TIMP-1, to restore the dynamic balance, in oreder to reverse ventricular remodeling, improving heart function,this a role in the treatment of heart failure.