[關(guān)鍵詞]
[摘要]
目的 探討注射用益氣復(fù)脈(凍干)(YQFM)對(duì)心力衰竭合并高血壓大鼠的藥效作用及可能的代謝通路。方法 構(gòu)建結(jié)扎腹主動(dòng)脈及腎動(dòng)脈導(dǎo)致的心衰合并高血壓大鼠模型,根據(jù)血壓值隨機(jī)分為模型組和YQFM組;假手術(shù)組進(jìn)行同樣操作但不結(jié)扎。每天尾iv給藥1次,連續(xù)給藥14 d。給藥前后采用八通道無(wú)創(chuàng)血壓儀檢測(cè)大鼠血壓;采用超聲診斷儀檢測(cè)大鼠心功能;采用ELISA法檢測(cè)給藥后大鼠血清心衰相關(guān)生化指標(biāo)肌酸激酶同工酶(CK-MB)、心肌特異性肌鈣蛋白T(cTnT)、腦鈉肽(BNP)、氨基端前心鈉肽(NT-proANP)和乳酸脫氫酶(LDH),血壓相關(guān)生化指標(biāo)腎素(Renin)、血管緊張素Ⅱ(Ang Ⅱ)、血管緊張素轉(zhuǎn)化酶1(ACE1)、血管緊張素原(aGT)水平;采用液相色譜質(zhì)譜聯(lián)用(LC-MS)法分析大鼠血清差異代謝物,將篩選出的差異性代謝物進(jìn)行代謝通路富集分析。結(jié)果 與假手術(shù)組相比,模型組大鼠左室射血分?jǐn)?shù)(LVEF)、左室短軸縮短率(LVFS)顯著降低(P<0.001),收縮壓(SBP)顯著升高(P<0.001),NT-proANP、BNP、CK-MB、cTnT、LDH、Renin、aGT、ACE1和AngⅡ水平均顯著升高(P<0.001);與模型組相比,YQFM組的LVEF、LVFS均顯著升高(P<0.001),SBP顯著降低(P<0.001),血清NT-proANP、BNP、CK-MB、cTnT、LDH、Renin、aGT、ACE1和AngⅡ水平顯著降低(P<0.001)。YQFM可能的作用通路為戊糖、葡萄糖醛酸轉(zhuǎn)換,醚脂代謝,甘油磷脂代謝,嘌呤代謝及色氨酸代謝。結(jié)論 YQFM可以改善心衰合并高血壓大鼠的心功能、血壓水平及相關(guān)生化指標(biāo),其可能的作用代謝通路為戊糖、葡萄糖醛酸轉(zhuǎn)換,醚脂代謝,甘油磷脂代謝,嘌呤代謝及色氨酸代謝。
[Key word]
[Abstract]
Objective To investigate the pharmacodynamic effect and possible metabolic pathway of Yiqi Fumai Lyophilized Injection (YQFM) on rats with heart failure and hypertension. Methods Heart failure with hypertension rats induced by ligation of abdominal aorta and renal artery were constructed. According to the blood pressure values were randomly divided into model group and YQFM group; another rats were taken as the sham-operated group for the same operation without ligation. The drug was given once a day for 14 days by tail iv. The cardiac function of rats was detected by ultrasonic diagnostic apparatus and the blood pressure of rats was detected by eight-channel non-invasive blood pressure meter before and after administration. Serum CK-MB, cTnT, BNP, NT-proANP, LDH, Renin, Ang II, ACE1 and aGT level were detected by ELISA. LC-MS was used to analyze the differential metabolites in rat serum to find differential metabolites and metabolic pathways. Results Compared with sham-operated group, the LVEF and LVFS of the model group were significantly decreased (P<0.001), the SBP of the model group increased significantly after modeling (P<0.001), and the levels of NT-proANP, BNP, CK-MB, cTnT, LDH, Renin, aGT, ACE1 and AngII in the model group were significantly increased (P<0.001). Compared with the model group, the LVEF and LVFS of YQFM group were significantly increased (P<0.001), SBP was significantly decreased after administration of YQFM (P<0.001), the levels of NT-proANP, BNP, CK-MB, cTnT, LDH, Renin, aGT, ACE1 and AngII in serum were significantly decreased after YQFM administration (P<0.001). The possible action pathway of YQFM pathway may be pentose, glucuronate interconversions, ether lipid metabolism, glycerophospholipid metabolism, purine metabolism and tryptophan metabolism. Conclusion YQFM can improve the heart function,blood pressure level and related biochemical indexes of rats with heart failure and hypertension. The metabolic pathways may be pentose, glucuronate interconversions, ether lipid metabolism, glycerophospholipid metabolism, purine metabolism and tryptophan metabolism.
[中圖分類號(hào)]
R285.5
[基金項(xiàng)目]