机构地区:[1]宁夏医科大学总医院临床药理研究室,银川750004 [2]宁夏医科大学总医院药剂科,银川750004 [3]宁夏医科大学药学院,银川750004
出 处:《中国临床药理学杂志》2017年第4期338-342,共5页The Chinese Journal of Clinical Pharmacology
基 金:国家自然科学基金资助项目(81260509)
摘 要:目的研究苦参碱对左室肥厚大鼠的心功能和左室重塑的改善作用。方法按照体重将健康成年雄性SD大鼠随机分为6组(各12只):正常组、模型组、对照组(200 mg·kg^(-1)·d^(-1)苦参碱)、大中小3个剂量(200,100,50 mg·kg^(-1)·d^(-1)苦参碱)实验组;模型组与实验组经皮下注射5 mg·kg^(-1)·d^(-1)异丙肾上腺素(ISO)制备大鼠左室肥厚模型,正常组和对照组按10 m L·kg^(-1)·d^(-1)灌胃0.9%Na Cl,每天1次,连续7 d。给药后第8天,用生物机能实验系统评价心功能,用HE染色法观察心肌细胞形态学变化,以酶联免疫吸附法检测血清胰岛素样生长因子^(-1)(IGF^(-1))、转化生长因子-β1(TGF-β1)水平,用实时荧光定量PCR法测定心肌组织IGF^(-1)、TGF-β1基因表达水平。结果相关药物处理后,正常组、模型组、对照组、大中小3个剂量实验组的血清IGF^(-1)水平分别为(2.04±0.52),(3.66±0.97),(2.08±0.95),(1.98±0.98),(1.93±0.78),(1.59±0.48)ng·m L^(-1);这6组的TGF-β1水平分别为(94.11±10.63),(139.98±37.64),(90.36±30.02),(84.55±45.70),(74.74±42.18),(72.84±21.43)pg·m L^(-1),与模型组比较,各组动物上述指标水平差异有统计学意义(P<0.05)。相关药物处理后,正常组、模型组、对照组、大中小3个剂量实验组的IGF^(-1)基因表达水平分别为3.34±3.27,10.91±7.44,3.09±1.86,0.62±0.44,0.64±0.26,1.00±0.35;这6组的TGF-β1基因表达水平为0.70±0.67,10.97±9.86,0.63±0.32,1.25±0.98,1.76±2.40,0.86±0.46,与模型组比较,各组动物上述指标水平差异有统计学意义(P<0.01)。结论苦参碱对ISO所致左室肥厚大鼠的心功能降低具有明显的改善作用,同时对导致心脏肥厚的细胞因子具有调控作用。Objective To investigate the effect of matrine on the cardiac function and left ventricular remodeling in rats with isoproterenol( ISO)- induced cardiac hypertrophy. Methods Seventy- two adult male SD rats were randomly divided into six groups as follows: normal group,model group,control group( matrine 200 mg·kg^-1·d^-1)large-,medium- and small- dose experimental groups( matrine 200,100,50 mg ·kg^-1·d^-1),and there were 12 rats in each group. The 5 mg·kg^-1·d^-1oproterenol( ISO) was subcutaneously injected to establish the model of chronic pathological left ventricular hypertrophy in model group and experimentalgroups. The 0. 9% Na Cl was administrated to rats in normal group and control group. The aforementioned medications were offered once daily to 12 rats of each group for 7 successive days. On day 8,cardiac function was evaluated by the biological function experiment system. The hematoxylin- eosin staining was used to observe pathological morphology changes of the left ventricular tissues. Insulin- like growth factor^(-1)( IGF^-1) and transforming growth factor- β1( TGF- β1) levels in serum were determined by ELISA. Expression levels of IGF^-1and TGF- β1genes in myocardial tissues were detected by real time fluorescence quantitative PCR method. Results After drug- concerned treatment,serum IGF^-1 levels in normal group,model group,control group,large-,medium- and small- dose experimental groups were separately( 2. 04 ± 0. 52),( 3. 66 ± 0. 97),( 2. 08 ± 0. 95),( 1. 98 ± 0. 98),( 1. 93 ± 0. 78) and( 1. 59 ± 0. 48) ng ·m L^-1 moreover,serum TGF- β1levels in those groups were( 94. 11 ± 10. 63),( 139. 98 ± 37. 64),( 90. 36 ± 30. 02),( 84. 55 ± 45. 70),( 74. 74 ± 42. 18) and( 72. 84 ± 21. 43) pg·m L^-1 In contrast with model group,the serum IGF^-1 or TGF- β1levels were lowered in other groups( P〈0. 05). Similarly,expression levels of cardiac IGF^-1 genes in normal group,model group,control group,large-,medi
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