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PI3Kγ抑制剂AS605240对异丙肾上腺素诱导大鼠心肌肥厚和纤维化的拮抗效应 被引量：3

The Antagonistic Effect of PI3K-gamma Inhibitor AS605240 on Cardiac Hypertrophy and Cardiac Fibrosis Induced by Isoproterenol In Rats
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摘要 目的研究磷脂酰肌醇3-激酶γ(PI3Kγ)小分子抑制剂AS605240对异丙肾上腺素(isoproterenol,ISO)诱导大鼠心肌肥厚和纤维化的治疗作用,并初步探讨其作用机制。方法健康雄性Wistar大鼠30只,随机分为3组(n=10),分别为ISO模型组、AS605240治疗组和正常对照组(空白组)。ISO模型组、AS605240治疗组皮下注射ISO 10 mg/(kg.d)×3 d,再5 mg/(kg·d)×11 d,复制大鼠心肌肥厚和纤维化模型,空白组注射相同体积的生理盐水;建模第2 d,AS605240治疗组给予AS605240 50 mg/(kg·d),ISO模型组和空白组给予等体积0.5%羧甲基纤维素,共给药14 d。末次给药后24 h,称取大鼠心脏质量和体质重,心脏HE染色观察组织学改变并评分,测量大鼠心重指数(HW/BW)、心功能、胶原容积分数(CVF)等。结果与正常对照组相比,ISO模型组大鼠HW/BW增加(P<0.05),心肌细胞间有大量胶原增生,心功能降低,胶原蛋白含量增加(P<0.05)。与ISO模型组大鼠相比,AS605240治疗组大鼠HW/BW降低(P<0.05),心功能有明显改善,心肌细胞间胶原沉积减少(P<0.05)。结论 AS605240对ISO引起的大鼠心肌纤维化具有一定的改善作用。 Objective To investigate the therapeutic effect of PI3Kγ inhibitor AS605240 on cardiac hypertrophy and cardiac fibrosis induced by Isoproterenol in rats.Methods Wistar rats were randomly divided into three groups（n=10）,control group,ISO group（vehicle group） and AS605240 group.The rats in control group without any treatment.The rats in ISO and AS605240 group were given ISO 10 mg/kg for 3 days and 5 mg/kg for another 11 days by subcutaneous injection to prepare the animal model of cardiac fibrosis.Rats in AS605240 group were given AS605240 50 mg/（kg·d） by intraperitoneal injection continuously for 14 days.The vehicle group received the intraperitoneal injection of an equal volume of 0.5% carboxymethylcellulose.Twenty-four hours after the last treatment,rats were sacrificed.Heart,body weight,cardiac function and the CVF were measured.Results Compared with the control group,the HW/BW of ISO group was increased significantly（P0.05） with a increased collagen inter cardiac muscle cells（P0.05）.Compared with ISO group, histological examination of the heart showed that AS605240 significantly relieved the rat cardiac fibrosis and reduced heart/body weight ratios in experimental cardiac fibrosis（P0.05）.Conclsuion AS605240 may be an effective antagonist for cardiac hypertrophy and cardiac fibrosis.
作者 宋丽芳 蒋维 卿勇 胡小红 李怡 童擎一 吴晓华
机构地区 四川大学华西医院生物治疗国家重点实验室
出处 《四川大学学报（医学版）》 CAS CSCD 北大核心 2011年第4期471-474,共4页 Journal of Sichuan University(Medical Sciences)
基金 国家"重大新药创制"科技重大专项项目(项目编号2009ZX09102-045) 教育部留学回国人员科研启动基金(项目编号JS20081007506765)资助
关键词 异丙肾上腺素 心肌纤维化 磷脂酰肌醇-3激酶γ AS605240 Isoproterenol Cardiac fibrosis PI3Kγ AS605240
分类号 R965 [医药卫生—药理学]
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参考文献11

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二级参考文献13

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共引文献2

同被引文献34

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四川大学学报（医学版）
2011年 第4期

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