祛痰通阳汤对慢性心衰大鼠心肌损伤的保护作用及机制

Effect and Mechanism of Qitongyangqutan Decoction on Myocardial in Rats with Chronic Heart Failure

目的:观察不同剂量祛痰通阳汤对慢性心衰大鼠心肌损伤的保护作用及可能机制。方法:将90只Wistar大鼠随机均分正常组、模型组、卡托普利组、祛痰通阳汤低、中、高剂量六组。为建立慢性心力衰竭模型,除正常组外的五组大鼠均以2ml/kg给予阿霉素腹腔,一周1次,共6周。注射造模成功后次日进行灌胃给予对应的不同药物,连续给药治疗四周后,应用ELISA法测定各组大鼠血浆脑尿钠肽(Brain natriuretic peptide,BNP)水平,称重计算心脏质量指数并采用投射电镜观察心肌细胞结构,通过实时荧光定量PCR法测定检测Kelch样环氧氯丙烷相关蛋白-1 (epoxy chloropro-pane Kelch sample related protein-1,Keap1)和核因子E2相关因子2(nuclearfactor erythroid-2 related factor 2,Nrf2)mRNA的表达。结果:1.电镜结果显示:正常组肌丝排列规则,肌节结构清晰,心肌细胞线粒体清晰且形态正常;细胞核发育良好,无空泡以及集块现象。模型组肌原纤维排列紊乱,心肌细胞线粒体形态异常,排列不齐,增生明显,有空泡现象形成。卡托普利组及祛痰通阳汤高剂量组电镜肌原纤维排列基本整齐,线粒体未见明显肿胀,线粒体嵴密集,优于中药低剂量组及中剂量组。2.卡托普利组、中药高剂量组大鼠血浆BNP水平较模型组显著降低(P<0.01)。3.与模型组相比,中药高剂量组和卡托普利组心脏质量指数均显著降低(P<0.05)。4.卡托普利组及祛痰通阳汤高剂量组心肌组织Keap1 m RNA表达与模型组相比显著降低(P<0.05);卡托普利组及祛痰通阳汤高剂量组心肌组织Nrf2 m RNA表达与模型组的相比显著提高(P<0.05)。结论:高剂量祛痰通阳汤可显著减轻慢性心衰大鼠的心肌损伤,可能与抑制Keap1 m RNA的表达及增强Nrf2 m RNA表达,进而抗心肌氧化损伤有关。

Objective: To observe the protective effect and mechanism of different doses of Tongyang Decoction on myocardial injury in rats with chronic heart failure. Methods: 90 healthy Wister rats were randomly divided into 6 groups. They were normal group,model group, captopril group, low-dose Chinese herbal medicine group, middle-dose Chinese herbal medicine group and high-dose Chinese herbal medicine group. Chronic heart failure model were established in the rat model by intraperitoneal injection of Adriamycin at 2 m L/kg once a week for 6 weeks. After the successful modeling, the intragastric administration was carried out the next day, and the continuous administration was used for four weeks. The plasma Brain natriuretic peptide(BNP) levels in each group were determined by ELISA. The heart mass index was calculated and the myocardial was observed by electron microscopy. Epoxy chloropro-pane Kelch sample related protein-1(Keap1) and nuclearfactor erythroid-2 related factor 2(Nrf2)mRNA were determined by real-time fluorescent quantitative PCR. Results: 1. The results of electron microscopy showed that the myofilament in the normal group was arranged regularly,the sarcomere structure was clear, the mitochondria of the cardiomyocytes were clear and the morphology was normal, there was no vacuolization and agglomeration. The myofibrils in the model group were disordered and the mitochondrial morphology of the cardiomyocytes was abnormal, unevenly arranged, the proliferation was obvious, and vacuoles were formed. The myofibrillar of captopril group and the high dose group of Tongtongyang decoction were neatly arranged, the mitochondria showed no obvious swelling, and the mitochondria were dense, which was better than the low dose group and the middle dose group. 2.The plasma BNP level in the captopril group and the high-dose group of rats was lower than that in the model group, which was significantly(P<0.01). 3.The heart quality index of the high-dose Chinese medicine group and the captopril group was significantly lower than that of the model group(P<0.05). 4. The expression of Keap1 m RNA high-dose Chinese medicine group and the captopril group was significantly lower than that of the model group(P<0.05) However, the Nrf2 m RNA of the high-dose Chinese medicine group and the captopril group was obviously higher than that of the model group(P<0.05). Conclusion: High-dose Qitongyang Decoction can significantly alleviate myocardial injury in rats with chronic heart failure. which may be related to the inhibition of Keap1 m RNA expression and enhancement of Nrf2 m RNAexpression,.