目的:探讨蜂胶总黄酮(TFP)对慢性心力衰竭大鼠心肌细胞凋亡的影响及其可能机制。方法:随机选取6只雄性SD大鼠为正常对照(NC)组;余下大鼠采用腹腔注射阿霉素造模,将造模成功的大鼠随机分成5组(n=6):慢性心力衰竭模型(CHF)组、蜂胶总黄酮低剂量(LD)组、蜂胶总黄酮中剂量(MD)组、蜂胶总黄酮高剂量(HD)组和地高辛(DIG)组。6周后通过生物信号系统记录大鼠血流动力学相关指标;检测各组大鼠血浆中脑钠肽(BNP)、心肌肌钙蛋白I(c Tn I)、肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)含量;取材后HE和Masson染色观察心脏结构改变及胶原纤维增生情况;Western blot检测缝隙连接蛋白43(P-Cx43)表达水平;TUNEL法检测心肌细胞凋亡。结果:与NC组相比,CHF组大鼠心脏血流动力学指标左室峰压(LVSP)及左室内压变化速率(±d P/dtmax)绝对值明显下降(P〈0.01),左室舒张期末压(LVEDP)明显升高(P〈0.01);血浆中BNP、c Tn I、TNF-α及IL-6含量均明显升高(P〈0.01);与CHF组相比,MD、HD组大鼠心脏血流动力学指标LVSP和±d P/dtmax绝对值明显升高(P〈0.05),LVEDP明显降低(P〈0.01),LD组LVEDP明显降低(P〈0.01),LVSP和±d P/dtmax变化均不明显。MD、HD组大鼠血清中BNP、c Tn I、TNF-α及IL-6含量明显降低(P〈0.01),LD组各指标变化不明显;Western blot结果显示:与NC组相比,CHF组P-Cx43条带明显增粗,给予TFP灌胃后,随着TFP剂量的增加,TFP各组PCx43条带逐渐变细变淡;进一步半定量分析显示,与NC组相比,各组中P-Cx43表达量显著升高(P〈0.01);与CHF组相比,TFP各组P-Cx43表达量均降低;MD组P-Cx43表达量低于LD组(P〈0.01),高于HD组(P〈0.05);CHF组心肌细胞凋亡指数(%)(22.61±3.39)较NC组(1.12±0.24)明显增高(P〈0.01);与CHF组相比,蜂胶总黄酮LD、MD、HD组心肌细胞凋亡指数(%)分
Objective: To investigate the effects of total flavonoids of propohs(TFP) on apoptosis of myocardial cells of chronic heart fail- ure and its possible mechanism in rats. Methods: Six male SD rats were randomly selected as normal control group,the remaining rats were made as chronic heart failure (CHF) model by intraperitoneal injection of adriamycin. The rats in the successful model were randomly divided into five groups ( n = 6) : CHF group, total flavonoids of propolis low dose group(LD group), total flavonoids of propohs middle dose group (MD group), total flavonoids of propolis high dose group(HD group), digoxin group( DIG group). After six week treatment, cardiac function indexes of rats were recorded by signal acquisition system; brain natriuretic peptide(BNP), cardiac troponin I(cTnI), tumor necrosis factor-a (TNF-a) and interleukin-6(IL-6) content in plasma were detected; Myocardial morphological changes and collagen fiber hyperplasia by HE and Masson staining were observed; Myocardial apoptosis was detected with TUNEL method and protein connexin 43(P-Cx43) expression was detected by Western blot method. Results: Compared with NC group, left ventricular systolic pressure(LVSP) and maximal rise/fall velocity of left ventriculad pressure( ±dP/dtm,=)absolute value in CHF group were significantly lowered (P 〈 0.01 ) while left ventricular end diastolic pressure(LVEDP) was increased significantly ( P 〈 0.01 ); Contents of plasma BNP, cTnI, TNF-aand IL-6 in the CHF group were significantly improved ( P 〈 0.01). Compared with CHF group, LVSP, + dP/dtmax, absolute value in MD and HD groups were increased ( P 〈 0.05), and LVEDP was significantly lowered ( P 〈 0.01) ; LVEDP in LD group was significantly lowered ( P 〈 0.01), changes in LVSP and ± dp/dtmmax absolue value were not obvious ( P 〉 0.05). BNP, cTnI, TNF-a and IL-6 contents in MD and liD groups were significantly reduced( P 〈 0.01), but t