摘要
目的:本实验主要研究卡托普利、益气温阳活血化瘀中药心复康口服液对经腹主动脉部分缩窄致压力超负荷性充血性心力衰竭(congestive heart failure, CHF)的大鼠模型心肌组织葡萄糖代谢关键物质葡萄糖转运蛋白4((glucose transportcrs protein 4, GLUT4))的影响,探讨在充血性心力衰竭发生、发展过程中葡萄糖代谢中GLUT4蛋白表达改变的机制以及改善葡萄糖代谢途径治疗充血性心力衰竭的可能机制。
方法:采用腹主动脉部分缩窄致压力超负荷性心肌肥厚制作充血性心力衰竭大鼠模型,将80只SD雄性大鼠随机平均分为假手术组(Sham operation, SH)、腹主动脉缩窄模型组(Coarctation of abdominal aorta, CAA)、卡托普利治疗组(Captopril intervention, CAP)、心复康口服液治疗组(Xin Fu Kang Koufuye, XFK)四组。在6周及10周时测量心衰大鼠心功能参数,用Westen Blot方法测定大鼠心肌GLUT4蛋白的表达灰度值,分别观察比较四组大鼠第6周、第10周心功能和GLUT4蛋白表达的变化。
结果:1、心功能的变化:(1)6周时:CAA组较SH组HR、SAP、DAP、LVEDP、LVMI显著升高(P<0.01),+dp/dtmax、-dp/dtmax显著降低(P<0.01)。CAP组、XFK组较SH组HR、DAP、LVEDP显著升高(P<0.01),+dp/dtmax、-dp/dtmax显著降低(P<0.01)。CAP组、XFK组较CAA组HR、LVMI、DAP、LVEDP显著降低(P<0.01),+dp/dtmax、-dp/dtmax显著升高(P<0.01)。XFK组与CAP组相比,+dp/dtmax的改善优于CAP组(P<0.05),其余各项指标相比无差异(P>0.05)。(2)10周时:CAA组较SH组SAP、DAP、HR、LVEDP、LVMI显著升高,+dp/dtmax、-dp/dtmax显著降低(P<0.01)。CAP组、XFK组较SH组LVEDP显著升高(P<0.01),+dp/dtmax、-dp/dtmax较CAA组显著降低(P<0.01)。CAP组、XFK组较CAA组SAP、LVMI、HR、DAP、LVEDP显著降低(P<0.01),+dp/dtmax、-dp/dtmax较CAA组显著增高(P<0.01)。XFK组与CAP组相比各项心功能指标无差异(P>0.05)。(3)CAA组大鼠10周较6周时LVMI、LVEDP时升高(P<0.05),+dp/dtmax,-dp/dtmax下降(P<0.05)。CAP组、XFK组大鼠10周较6周时LVMI、LVEDP下降(P<0.05),+dp/dtmax显著升高(P<0.05),-dp/dtmax无明显变化。
2、6周时GLUT4蛋白表达灰度值(GLUT4/GAPDH)的变化:(1)CAA组在6周时GLUT4蛋白表达的灰度值较SH组、CAP组及XFK组明显降低(P<0.01)。(2)CAP组6周时GLUT4蛋白的表达较SH组明显降低(P<0.01);但和XFK组比较GLUT4蛋白的表达没有明显差异(P>0.05)。(3) XFK组6周时GLUT4蛋白的表达较SH组明显降低(P<0.01)。
3、10周时GLUT4蛋白表达灰度值(GLUT4/GAPDH)的变化:(1)CAA组在10周时GLUT4蛋白表达灰度值较SH组、CAP组及XFK组明显降低(P<0.01)。(2)CAP组10周时GLUT4蛋白表达较SH组明显降低(P<0.01),和XFK组没有显著性差异(P>0.05)。(3) XFK组10周时GLUT4蛋白表达与SH组没有明显差异(P>0.05)。
结论:(1)高压力负荷性心力衰竭大鼠心功能损害时心肌组织葡萄糖转运蛋白4的表达降低。(2)ACEI类药物卡托普利对高压力负荷性心力衰竭大鼠心功能及葡萄糖转运蛋白4的表达具有明显的改善作用。(3)具有益气温阳、活血化瘀作用的心复康口服液对高压力负荷性心力衰竭大鼠心功能及葡萄糖转运蛋白4的表达具有明显的改善作用。
Objective: The paper focuses on the effect of captopril and traditional Chinese medicine Xin Fu Kang Koufuye on function of invigoration QI warming YANG and promoting blood circulation to removing blood stasis on Glucose Transporter Protein 4 of myocardium in pressure overload-induced left ventricular hypertrophy in rats. Also it discusses the change of expression for GLUT4 of the glucose metabolism in process of CHF as well as the mechanism for ameliorate of the glucose metabolism in CHF.
Methods: The method of coarctation of abdominal aorta (CAA) in male SD rats was taken to make high pressure overload-induced left ventricular hypertrophy model of CHF. 80 SD rats were randomly divided into four groups: Sham operation(SH), Coarctation of abdominal aorta model group (CAA), Captopril Tablets cure group(CAP) and Xin Fu Kang Koufuye group(XFK). And then measure the function of heart and grayscale of GLUT4 protein by Western Blot after six and ten weeks respectively and observe the change of them.
Result: 1.The function of Heart: (1) In the time of 6 week: compare with SH group, HR, SAP, DAP, LVEDP and LVMI of CAA group increased(P<0.01), +dp/dtmax and -dp/dtmax decreased(P<0.01). Compare with SH group , HR, DAP, LVEDP of CAP and XFK group increased(P<0.01), +dp/dtmax and -dp/dtmax decreased(P<0.01). Compare with CAA group, HR, LVMI, DAP and LVEDP of CAP and XFK group decreased (P<0.01), +dp/dtmax and -dp/dtmax increased (P<0.01). Betwe- en CAP and XFK group, all the stat value is same (P>0.05) except +dp/dtmax(P<0.05). (2) In the time of 10 week: compare with SH group, SAP, DAP, HR, LVEDP and LVMI of CAA group increased, +dp/dtmax and -dp/dtmax decreased (P<0.01). Compare with SH group, LVEDP of CAP and XFK group decreased(P<0.01), +dp/dtmax and -dp/dtmax increased (P<0.01). Compare with CAA group, SAP, LVMI, HR, DAP and LVEDP of CAP and XFK group decreased(P<0.01), +dp/dtmax and -dp/dtmax increased(P<0.01). Between CAP and XFK group, all the stat value is same(P>0.05). (3) Compare with 6th, LVMI and LVEDP of CAA group in the 10th increased (P<0.05), +dp/dtmax and -dp/dtmax decreased (P<0.05). LVMI and LVEDP of CAP and XFK group in the 10th decreased (P<0.05), and +dp/dtmax increased(P<0.05) with -dp/dtmax not change.
2.the Grayscale(GLUT4/GAPDH)of GLUT4 protein in the 6th week: (1) The study shows that CAA group GLUT4 protein ma- rkedly decreased compare with SH group, CAP group and XFK group (P<0.01). (2) In the CAP group the grayscale of GLUT4 protein markedly decreased compare with SH group (P<0.01) while indiscriminate compare with XFK group (P>0.05). (3) In the XFK group the grayscale of GLUT4 protein markedly decreased compare with SH group(P<0.01).
3.the Grayscale(GLUT4/GAPDH) of GLUT4 protein in the 10th week: (1)The study shows that the grayscale of GLUT4 protein of CAA group markedly decreased compare with SH group, CAP group and XFK group (P<0.01). (2) In the CAP group the grayscale of GLUT4 protein markedly decreased compare with SH group(P<0.01) while indiscriminate compare with XFK gro- up(P>0.05). (3) In the XFK group the grayscale of GLUT4 pro- tein is indiscriminate compare with SH group(P>0.05).
Conclusion: (1)The expression of glucose transporter protein 4 is decreased with the harmfulness of heart function by high pressure overload-induced CHF. (2) Captopril can enhance and improve the heart function and the expression of GLUT4 of myocardial of Rat by high pressure overload-induced CHF. (3) Xin Fu Kang Koufuye on function of invigoration QI warming YANG and promoting blood circulation to removing blood stasis can enhance and improve the heart function and the expression of GLUT4 of myocardial of Rat by high pressure overload-induced CHF.
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