不同剂量万古霉素对慢性心力衰竭大鼠心功能、 肾功能及神经内分泌因子的影响及其血药浓度变化  

Effects of different doses of vancomycin on cardiac function,renal function,and neuroendocrine factors in rats with chronic heart failure and their changes of plasma concentration

作　　者：丁小琼[1] 王清传[2] 王元标[1] 张志敏 DING Xiaoqiong;WANG Qingchuan;WANG Yuanbiao;ZHANG Zhimin(Department of Accredited Outpatient,General Hospital of Xinjiang Military Command,Urumqi 830000,Xinjiang,China;Department of Cadre Health,General Hospital of Xinjiang Military Command,Urumqi 830000,Xinjiang,China;Department of Cardiology,General Hospital of Xinjiang Military Command,Urumqi 830000,Xinjiang,China)

机构地区：[1]新疆军区总医院派驻门诊部,新疆乌鲁木齐市830000 [2]新疆军区总医院干部保健科,新疆乌鲁木齐市830000 [3]新疆军区总医院心内科,新疆乌鲁木齐市830000

出　　处：《广西医学》2023年第5期567-574,579,共9页Guangxi Medical Journal

摘　　要：目的探讨不同剂量万古霉素对慢性心力衰竭(CHF)大鼠心功能、肾功能及神经内分泌因子的影响及其血药浓度变化。方法取12只大鼠作为假手术组。取60只大鼠建立CHF模型,将55只造模成功的大鼠随机分为CHF组(11只)、低剂量万古霉素组(11只)、中剂量万古霉素组(11只)、高剂量万古霉素组(11只)及药物对照组(11只)。分别给予低剂量万古霉素组、中剂量万古霉素组、高剂量万古霉素组大鼠经尾部注射25 mg/kg、50 mg/kg、100 mg/kg的万古霉素,给予药物对照组大鼠卡托普利灌胃,给予假手术组和CHF组大鼠等体积生理盐水灌胃。检测各组大鼠心功能指标[左心室舒张末期内径(LVEDD)、收缩末期内径(LVESD)、左心室射血分数(LVEF)和左室短轴缩短率(LVFS)]、肾功能指标[血清肌酐、血清尿素氮和24 h尿蛋白(UP24)]、神经内分泌因子[血清血管紧张素Ⅱ(AngⅡ)、醛固酮和心钠素]水平;采用HE染色观察各组大鼠心肌组织、肾组织的病理学变化;采用Western blot检测各组大鼠心肌组织AngⅡ、醛固酮和心钠素的蛋白表达水平;采用吸波面积法检测不同剂量万古霉素组的血药浓度。结果(1)与假手术组相比,CHF组大鼠的LVEDD、LVESD、血清肌酐水平、血清尿素氮水平和UP24水平均升高,LVEF、LVFS均降低(均P<0.05);与CHF组相比,各剂量万古霉素组大鼠的LVEDD、LVESD、血清肌酐水平、血清尿素氮水平和UP24水平均降低,LVEF、LVFS均升高(均P<0.05),除肾功能指标外,其余指标总体上均呈剂量依赖性变化。(2)HE染色结果显示,CHF组大鼠心肌细胞水肿,细胞浆染色加深,细胞体积缩小,可见空泡;肾小球间质增加,肾间质增宽。各药物干预组大鼠的心肌组织和肾脏组织损伤均有所减轻,其中高剂量万古霉素和药物对照组大鼠心肌损伤的改善最为显著,中剂量万古霉素组及药物对照组大鼠肾组织损伤的改善最为显著。(3)与假手术组相Objective To investigate the effects of different doses of vancomycin on cardiac function,renal function and neuroendocrine factors in rats with chronic heart failure(CHF)and their changes of plasma concentration.Methods A total of 12 rats were selected as sham operation group.Sixty rats were selected to establish CHF model,and 55 successful modeling rats were randomly divided into CHF group(11 rats),low-dose vancomycin group(11 rats),medium-dose vancomycin group(11 rats),high-dose vancomycin group(11 rats)or drug control group(11 rats).Rats in the low-,medium-and high-dose vancomycin groups received caudal injection of vancomycin with 25 mg/kg,50 mg/kg and 100 mg/kg,respectively,rats in the drug control group received intragastric administration of captopril,and rats in the sham operation group and the CHF group received intragastric administration of normal saline with the same volume.The levels of cardiac function indices in terms of left ventricular end-diastolic dimension(LVEDD),left ventricular end-systolic dimension(LVESD),left ventricular ejection fraction(LVEF),and left ventricular fraction shortening(LVFS),renal function indices with respect to serum creatinine,serum urea nitrogen,and 24-hour urinary protein(UP24),and neuroendocrine factors,namely,angiotensinⅡ(AngⅡ),aldosterone,and atrial natriuretic peptide in rats were detected in various groups.HE staining was used to observe pathological morphology of myocardial and kidney tissues in rats of various groups.The Western blot was employed to detect the protein expressions of AngⅡ,aldosterone,and atrial natriuretic peptide in myocardial tissues of rats in various groups.The plasma concentration of different doses of vancomycin was measured by the absorbing area method.Results(1)Compared with the sham operation group,LVEDD,LVESD,serum creatinine level,serum urea nitrogen level,and UP24 level of rats were increased,and LVEF and LVFS of rats were decreased in the CHF group(all P<0.05).Compared with the CHF group,LVEDD,LVESD,serum creatinine level,ser

关 键 词：慢性心力衰竭 万古霉素 心功能 肾功能 神经内分泌因子 血药浓度 大鼠 

分 类 号：R541.6[医药卫生—心血管疾病]