[關(guān)鍵詞]
[摘要]
目的 探討真武湯對(duì)慢性心力衰竭(CHF)大鼠的治療作用,并分析其潛在作用機(jī)制。方法 建立真武湯的HPLC特征圖譜;雄性SD大鼠隨機(jī)分為假手術(shù)組、模型組、陽(yáng)性藥卡托普利組(10 mg/kg)和真武湯低、中、高劑量(2.187 5、4.375、8.75 g/kg)組,除假手術(shù)組外,其余大鼠均通過(guò)結(jié)扎冠狀動(dòng)脈左前降支復(fù)制CHF大鼠模型,8周后ig給藥,共給藥4周。實(shí)驗(yàn)?zāi)┻M(jìn)行血流動(dòng)力學(xué)、臟器指數(shù)、HE染色檢測(cè),ELISA試劑盒測(cè)定大鼠血清血管緊張素II(Ang II)、醛固酮(ALD)、核轉(zhuǎn)錄因子-κB(NF-κB)、氨基末端腦鈉肽(NT-proBNP)、腫瘤壞死因子-α(TNF-α)、白細(xì)胞介素-6(IL-6)水平,Western boltting檢測(cè)心肌NF-κB蛋白表達(dá)情況。結(jié)果 真武湯HPLC圖譜中指認(rèn)出5個(gè)化學(xué)成分去甲烏藥堿、芍藥苷、白術(shù)內(nèi)酯III、6-姜辣素、去氫土莫酸;與模型組比較,真武湯給藥后能改善大鼠血流動(dòng)力學(xué)相關(guān)參數(shù)(P<0.05),降低臟器指數(shù)(P<0.05),改善心肌損傷,降低血清Ang II、ALD、NF-κB、NT-proBNP、TNF-α、IL-6水平及心肌NF-κB蛋白表達(dá)水平(P<0.05)。結(jié)論 真武湯能夠改善CHF,其機(jī)制可能與抑制腎素-血管緊張素-醛固酮系統(tǒng)(RAAS)/NF-κB/炎癥因子級(jí)聯(lián)反應(yīng)有關(guān)。
[Key word]
[Abstract]
Objective To investigate the therapeutic effect and potential mechanism of Zhenwu Decoction (ZWD) on chronic heart failure (CHF) rats. Methods HPLC fingerprint of ZWD was established. All male SD rats were randomly divided into the sham operation group, the model group, the low, medium and high dose ZWD group (2.187 5, 4.375, and 8.75 g/kg) and the captopril group (10 mg/kg). Except for the sham operation group, the rest of rats were all established into the CHF model rats by ligating the left anterior descending branch of the coronary artery, after 8 weeks, all rats were ig administration for 4 weeks. The hemodynamic, viscera index, HE dyeing test were conducted at the end of experiments. Serum angiotensin II (Ang II), aldosterone (ALD), nuclear factor kappa B (NF-κB), amino terminal brain natriuretic peptide (NT-proBNP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) were determinated by ELISA, and myocardial NF-κB protein expression was detected by Western blotting. Results Higenamine, paeoniflorin, atractylenolide III, 6-gingerol and dehydrotumulosic acid, the five constituents of Zhenwu Decoction, were identified by HPLC chart. Compared with the model group, the administration of the ZWD significantly improved the hemodynamic parameters (P<0.05), reduced the organ index (P<0.05) and improved myocardial injury, reduced the serum Ang II, ALD, NF-κB, NT-proBNP, TNF-α and IL-6 levels and the myocardial NF-κB protein expression (P<0.05). Conclusion HPLC results provided an evidence for the quality control and pharmacodynamic substance of ZWD. ZWD can ameliorate CHF, which may be related to the inhibition of renin-angiotensin-aldosterone system (RAAS)/NF-κB/inflammatory factor cascade reaction.
[中圖分類號(hào)]
R285.5
[基金項(xiàng)目]
國(guó)家自然科學(xué)基金資助項(xiàng)目(81773988);國(guó)家重點(diǎn)研發(fā)計(jì)劃項(xiàng)目(2017YFC1701600);安徽省科技重大專項(xiàng)(18030801131);安徽省地方科技創(chuàng)新項(xiàng)目示范(201907d07050002);全國(guó)大學(xué)生創(chuàng)新創(chuàng)業(yè)訓(xùn)練計(jì)劃項(xiàng)目(2017043)