5羟色胺2B受体阻滞剂对压力超负荷大鼠心功能的影响

Effects of serotonin 2Breceptor antagonist on cardiac function in rats with pressure overload

  • 摘要: 目的探讨5羟色胺2B受体阻滞剂(SB215505)在体干预对压力超负荷大鼠心功能的影响。方法成年雄性SD大鼠34只,体质量200~230g,随机分为假手术组14只,主动脉缩窄(AAC)组20只;术后第9周,将假手术组随机分为假手术8周组和假手术12周组(n=7),将AAC组随机分为SB215505组腹腔注射溶于二甲基亚砜(DMSO)浓度为2g/L的SB215505溶液,1mg/(kg·d),给药过程中死亡1只,n=5、AAC8周组(n=7)和AAC12周组(n=7),假手术12周组和AAC12周组腹腔注射等体积的DMSO溶液,立即处死假手术8周组和AAC8周组,并取心脏和血液标本;其余各组给药4周后处死并取心脏和血液标本。监测各组左心室质量指数(LVMI)、左心室心肌细胞横径(LVTDM),心肌细胞横截面积(CSA)及血浆脑钠尿肽含量;心脏彩色多普勒超声(彩超)评估假手术12周组、AAC12周组、SB215505组左心室心功能,蛋白印迹和免疫组化检测瞬时受体电位通道C亚族3型(TRPC3)蛋白表达水平。结果与假手术8周组比较,AAC8周组LVMI、LVTDM、CSA、血浆脑钠尿肽含量明显升高(均P<0.05)。与假手术12周组比较,AAC12周组LVMI、LVTDM、CSA、血浆脑钠尿肽含量、左心室收缩末期内径(LVESD)、TRPC3蛋白表达水平明显升高;而左心室射血分数(LVEF)、左心室缩短分数降低(均P<0.05)。与AAC12周组比较,SB215505组LVMI(1.95±0.13)比(2.39±0.35)mg/g、LVTDM(17.70±2.48)比(23.74±2.96)μm、CSA(279.1±74.2)比(442.4±132.7)μm2、血浆脑钠尿肽含量(108.5±19.7)比(583.5±82.4)ng/L、LVESD(4.15±0.95)比(4.81±0.05)mm、TRPC3蛋白表达水平(0.65±0.02比0.92±0.04)降低;而LVEF(0.77±0.01比0.69±0.03)、左心室缩短分数(0.40±0.01比0.34±0.02)升高(均P<0.05)。结论SB215505可能通过降低TRPC3表达水平,部分抑制心室重构,改善压力超负荷大鼠的心功能。

     

    Abstract: Objective To investigate the effect of intervention of serotonin 2Breceptor antagonist(SB215505)in vivo on cardiac function in pressure-overloaded rats. Methods Thirty-four adult male SD rats,weighing 200-230 g,were randomly divided into sham-operated group(n=14)and abdominal aorta coarctation(AAC)group(n=20).At the 9th week after the operation,rats in the sham-operated group were randomly divided into sham-operated8-week group and sham-operated 12-week group(n=7in each group),and rats in the AAC group were randomly divided into SB215505group(intraperitoneal injection of SB215505 with the dose of 1mg/(kg·d),which dissolved in DMSO at the concentration of 2mg/mL,and 1rat died during the injection;n=5,ACC 8-week group(n=7)and AAC12-week group(n=7). Sham-operated 8-week group and ACC 8-week group were killed immediately,and heart and blood samples were taken. Sham-operated 12-week group and ACC 12-week group received intraperitoneal injection of an equal volume of DMSO solution for 4weeks,and then were killed and the samples of heart and blood were taken. Left ventricular mass index(LVMI),left ventricular transdiameter of cardiomyocyte(LVTDM),cardiomyocytes surface area(CSA)and levels of BNP in the plasma were determined in each group. In the sham-operated 12-week group,ACC 12-week group and SB215505 group,left ventricular function was estimated by echocardiogram and the expression levels of transient receptor potential channel subtribe C type 3(TRPC3)protein were determined by Western blot and immunohistochemical method.Results Compared with the sham-operated 8-week group,LVMI,LVTDM,CSA and levels of BNP in the plasma were significantly increased in the AAC8-week group(all P<0.05). Compared with the sham-operated 12-week group,LVMI,LVTDM,CSA,levels of BNP in the plasma,left ventricular end systolic diameter(LVESD)and the expression levels of TRPC3 protein were significantly increased,while left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were decreased in the AAC12-week group(all P <0.05). Compared with the AAC12-week group,LVMI(1.95±0.13)vs(2.39±0.35)mg/g,LVTDM (17.70±2.48)vs(23.74±2.96)μm,CSA (279.1±74.2)vs(442.4±132.7)μm2,levels of BNP in the plasma (108.5±19.7)vs(583.5±82.4)ng/L,LVESD(4.15±0.95)vs(4.81±0.05)mmand expression levels of TRPC3protein(0.65±0.02 vs 0.92±0.04)were significantly decreased,while LVEF(0.77±0.01 vs 0.69±0.03)and LVFS(0.40±0.01 vs 0.34±0.02)were obviously increased in the SB215505group(all P<0.05). Conclusion SB215505 could partially inhibit ventricular remodeling and improve cardiac function in pressure-overloaded rats,which may attribute to the down-regulation of TRPC3 protein expression.

     

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