机构地区:[1]天津中医药大学,天津301617 [2]天津天士力之骄药业有限公司,天津300410 [3]天津市中药注射剂安全性评价企业重点实验室,天津300410 [4]天士力医药集团股份有限公司,天津300402
出 处:《药物评价研究》2023年第8期1673-1678,共6页Drug Evaluation Research
摘 要:目的探讨注射用益气复脉(冻干)(YQFM)对心力衰竭感染性休克大鼠的药效作用。方法通过结扎冠状动脉左前降支以及尾静脉推注脂多糖(LPS,25 mg·kg^(-1))的方法建立心力衰竭感染性休克大鼠模型,随机将造模后大鼠分为模型组,肾上腺素(10μg·kg^(-1))组,YQFM低、高剂量(232.2、464.3 mg·kg^(-1))组,联合给药(肾上腺素10μg·kg^(-1)+YQFM 464.3 mg·kg^(-1))组,假手术组进行同样操作但不结扎不推注LPS。造模后即给药,尾iv给药1次,模型组和假手术组大鼠给予等体积的0.9%氯化钠注射液。使用八通道无创血压仪检测造模前、造模后及给药后大鼠收缩压变化;ELISA法检测各组大鼠血清中脑钠肽(BNP)、氨基端前心钠肽(NT-proANP)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和超氧化物歧化酶(SOD)水平。结果各组大鼠的基础收缩压无显著性差异,与假手术组比较,造模各组大鼠收缩压显著降低(P<0.001);与模型组比较,各给药组大鼠收缩压显著回升(P<0.05、0.001)。与假手术组相比,模型组血清NT-proANP、BNP、CK-MB、LDH、ALT、AST水平显著升高(P<0.001),SOD水平显著降低(P<0.001);与模型组相比,肾上腺素组,YQFM 232.2、464.3 mg·kg^(-1)组和联合给药组的NT-proANP、BNP、CK-MB、LDH、ALT、AST水平均显著下降(P<0.05、0.01、0.001),肾上腺素组、YQFM 464.3 mg·kg^(-1)组和联合给药组SOD水平显著升高(P<0.05、0.01、0.001)。结论YQFM可以显著回升心力衰竭感染性休克大鼠的收缩压水平,改善血清中相关生化指标水平,并且与肾上腺素联合应用效果最好。Objective To investigate the effect of Yiqi Fumai Lyophilized Injection(YQFM)on heart failure with septic shock in rats.Methods The animal model of heart failure with septic shock in rats were established by ligating the left anterior descending coronary artery and injecting LPS(25 mg·kg^(-1))in tail vein.The rats were randomly divided into model group,epinephrine(10μg·kg^(-1))group,YQFM low dose and high dose(232.2 and 464.3 mg·kg^(-1)),and combined administration group(epinephrine 10μg·kg^(-1)+YQFM 464.3 mg·kg^(-1)).Administration immediately after molding,once in the tail iv.The rats in the model group and sham operation group were given 0.9%sodium chloride injection in equal volume.The rats of the sham operation group were performed the same operation without ligation and injection of LPS.The changes of systolic blood pressure(SBP)of rats before modeling,after modeling and after administration were detected by eight-channel non-invasive blood pressure meter.The serum levels of NT-proANP,BNP,CK-MB,LDH,ALT,AST and SOD were detected by ELISA.Results There was no significant difference in basal SBP among the groups.Except for the sham operation group,the SBP of the model rats was significantly lower than that of the sham operation group(P<0.001).Compared with the model group,the SBP of the rats increased after administration of the corresponding drugs(P<0.05,0.001).Compared with the sham operation group,the levels of serum NTproANP,BNP,CK-MB,LDH,ALT and AST in the model group were significantly increased(P<0.001),and the level of SOD was significantly decreased(P<0.001).Compared with the model group,the levels of NT-proANP,BNP,CK-MB,LDH,ALT and AST in the epinephrine group,YQFM 232.2,464.3 mg·kg^(-1) group,and combination therapy group were significantly decreased(P<0.05,0.01,0.001),and the levels of SOD were significantly increased in the epinephrine group,YQFM 464.3 mg·kg^(-1) group,and combination therapy group(P<0.05,0.01,0.001).Conclusion YQFM can significantly increase the SBP level of rats with he
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