卡托普利、心复康口服液对心衰大鼠心肌GLUT4的影响
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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.
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.
引文
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47 Fryer LG, Foufelle F, Barnes K, et al. Characterization of of glucose transport in skeletal muscle cells. Biochem J, 2002,363:167-174
48 Hirock T, Takashi HA, Kenjiro K. Protective Effect of the Angiotensin-Converting Enzyme inhibitor Captopril on po- stischemic Myocardial Damage in perfused Rat Heart. Japanese circulation Jaurnal,1997,61:687-694
49 Divisova J, Vavrinkova H, Tutterova M, et al. Effect of ACE Inhibitor Captopril and L-Arginine on the Metabo- lism And on Ischemia-Reperfusion Injury of the Isolated Rat Heart. Physiol Res, 2001,50:143-152
50 Katayama S, Inaba M, Maruno Y, et al. Glucose intolerance in spontaneously hypertensive and Wistar-Kyoto rats: enha- nced gene expression and synthesis of skeletal muscle glu- cose trans -porter 4. Hypertens Res,1997,20(4):279-286
51 陈德昌. 现代实用本草(上册). 人民卫生出版社, 1996, 681-691
52 程桂荣, 易胜中. 黄芪预处理大鼠心肌保护效应的实验研究. 高血压杂志, 2001,9(4):316-318
53 陈世宏, 叶耘, 尚正录. 黄芪保心汤抗心肌缺血与血管内皮保护作用研究. 中药药理与临床, 2005,21(5):43-44
54 曹宏先. 黄芪注射液治疗冠心病 80 例临床分析. 中医药, 1997,(5):15
55 胡元会, 车维新, 曹贵民, 等. 心复康口服液对大鼠实验心衰模型心肌 Ca2+定位及 Ca2+-ATPase 活性的影响. 中国中医学基础杂志, 1999,5(10):27-30
56 曹雪滨, 李培建, 黄河玲, 等. 心复康口服液对大鼠实验性心肌性心肌缺血的保护作用. 中国药科大学学报, 1998,29(Suppl):196-198
57 宋春宇, 毕会民. 葛根素对大鼠胰岛素刺激下骨骼肌细胞 膜 GLUT4 蛋 白 含 量 的 影 响 . 中 国 中 药 杂志,2004,2:172 -175
58 李娟娟, 毕会民. 葛根素对胰岛素抵抗大鼠脂肪细胞葡萄糖转运蛋白 4 的影响. 中国临床药理学与治疗学, 2004,9(8):885-888
59 张雷, 陈立梅, 倪红霞. 葛根素影响链脲佐菌素诱导糖尿病大鼠脂肪细胞葡萄糖转运蛋白 4 的表达. 中国临床康复. 2006,39:135-138
60 Guang CH, Fu-er LU, Dan J. Effect of Huanglian Jiedu Skeletal Muscle Tissues of Insulin Resistant Rats. Chin J Integr Med, 2007Mar,13(1):41-45
61 毛先睛, 欧阳静萍, 吴勇. 中药黄芪多糖对糖尿病大鼠心肌GLUT4表达的影响. 武汉大学学报(医学版), 26(4): 457-459
62 陈立梅, 王尔孚. 汉防己甲素影响糖尿病大鼠各组织葡萄糖转运蛋白 4 蛋白表达的意义. 中国临床康复, 2006, 19:86-88
63 王彬, 王宗仁, 李军昌, 等. 芪丹通脉片对大鼠缺血/再灌注损伤心肌细胞GLUT4的影响.心脏杂志, 2007,19(3): 255-257
1 Mueckler M. Family of glucose-transporter genes, Implica- tions for glucose homeostasis and diabetes. Diabetes, 1990, 39:6-11
2 Wood IS, Trayhurn P. Glucose transporters (GLUT and SG- LT):expanded families of sugar transport proteins. Br J Nutr, 2003,89:3-9
3 Joost HG, Thorens B. The extended GLUT-family of sugar/ polyol transport facilitators:nomenclature,sequence charac- teristics, and potential function of its novel members. Mol Membr Biol, 2001,18(4):247-256
4 Santalucia T, Camps M, Castello A, et al. Developmental regulation of GLUT-1 (erythroid/Hep G2) and GLUT-4 (muscle/fat) glucose transporter expression in rat heart, skeletal muscle, and brown adipose tissue. Endocrinology, 1992,130:837-846
5 Katz EB, Burcelin R, Tsao TS, et al. The metabolic cones-quences of altered glucose transporter expression in trans- genic mice . Mol Med, 1996,74:639-652
6 Li SH, McNeilj H. In vivo effects of vanadium on GLUT4 translocation in cardiac tissue of STZ-diabetic rats. Molec- ular and Biochemistry, 2001,217:127-132
7 Rea S, James DE. Moving GLUT4: the biogenesis and traf- ficking of GLUT4 storage vesicles. Diabetes, 1997,46: 1667-1677
8 Li D, Randhawa VK, Patel N, et al. Hyperosmolarity redu- ces GLUT4 endocytosis and increases its exocytosis from a VAMP2-independent pool in l6 muscle cells. Biol Chem, 2001,276:22883-22891
9 Bryant NJ, Govers R, James DE. Regulated transport of the glucose transporter GLUT4. Cell Biol, 2002,3:267-277
10 James DE, Strube M, Mueckler M. Molecular cloning and characterization of an insulin-regulatable glucose transpo- rter. Nature, 1989,338:83-87
11 Carte E, Gregor YD, Andre G. Stimulation of glucose trans- port in skeletal muscle by hypoxia. Appl Physiol. 1991,70 (4):1593-1600
12 Lawrence H. Young MD, Yin R, et al. Low-Flow Ischem- ia Leads to Translocation of Canine Heart GLUT-4 and G- LUT-1 Glucose Transporters to the Sarcolemma In Vivo. Circulation, 1997,95:415-422
13 殷仁富, 陈金明, 吴宗贵. 胰岛素促进犬缺血心肌 GLU- T4易位和葡萄糖摄取. 第二军医大学学报, 2001,22(2):112-114
14 Margareta K, Hans T, Santiago P. Insulin induces translo- cation of glucose transporter GLUT4 to plasma membrane caveolae in adipocytes. The Faseb Journal, 2002, 16(2): 249-251
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19 Mora S, Pessin JE. An adipocentric view of signaling and intracellular trafficking. Diabetes Metab, 2002,18:345–356
20 Hayashi T, Hirshman MF, Kurth EJ, et al. Evidence for 5-AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes, 1998,47:1369-1373
21 Fryer LG, Foufelle F, Barnes K, et al. Characterization of the role of the AMP-activated protein kinase in the stimulation of glucose transport in skeletal muscle cells. Biochem J, 2002,363(1):167-174
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34 Allard MF, Schonekess BO, Henning SL, et al. Contributi- on of oxidative metabolism and glycolysis to ATP product- ion in hypertrophied hearts. Heart Circ Physiol,36:742-750
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38 Lopaschuk GD ,Stanley WC. Glucose metabolism in the ischemic heart. Circulation,1997,95:313-315
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41 Roden M. How free fatty acids inhibit glucose utilization in human skeletal muscle. News Physiol Society, 2004,19:92 -96
42 冯兵, 徐静, 刘伟. 肥大心肌细胞能量代谢途径变化及药物干预效应研究. 重庆医学, 2006,35(8): 699-702
43 Jan WS, Hans JG, Sander G. Translocation of the glucose transporter GLUT4 in cardiac myocytes of the rat. Cell Biology,1991,88:7815-7819
44 Roland G, Adelle CF,David EJ. Insulin Increases Cell Surf- ace GLUT4 Levels by Dose Dependently DischargingGLUT4 into a Cell Surface Recycling Pathway. Molecular and Cellular Biology,2004,24:6456-6466
45 Cortright RN, Dohm GL. Mechanisms by which insulin and muscle contraction stimulate glucose transport. Can J Appl Physiol,1997,22:519-530
46 Hayashi T, Hirshman MF, Kurth EJ, et al. Evidence for 5-AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes, 1998, 47:1369-1373
47 Fryer LG, Foufelle F, Barnes K, et al. Characterization of of glucose transport in skeletal muscle cells. Biochem J, 2002,363:167-174
48 Hirock T, Takashi HA, Kenjiro K. Protective Effect of the Angiotensin-Converting Enzyme inhibitor Captopril on po- stischemic Myocardial Damage in perfused Rat Heart. Japanese circulation Jaurnal,1997,61:687-694
49 Divisova J, Vavrinkova H, Tutterova M, et al. Effect of ACE Inhibitor Captopril and L-Arginine on the Metabo- lism And on Ischemia-Reperfusion Injury of the Isolated Rat Heart. Physiol Res, 2001,50:143-152
50 Katayama S, Inaba M, Maruno Y, et al. Glucose intolerance in spontaneously hypertensive and Wistar-Kyoto rats: enha- nced gene expression and synthesis of skeletal muscle glu- cose trans -porter 4. Hypertens Res,1997,20(4):279-286
51 陈德昌. 现代实用本草(上册). 人民卫生出版社, 1996, 681-691
52 程桂荣, 易胜中. 黄芪预处理大鼠心肌保护效应的实验研究. 高血压杂志, 2001,9(4):316-318
53 陈世宏, 叶耘, 尚正录. 黄芪保心汤抗心肌缺血与血管内皮保护作用研究. 中药药理与临床, 2005,21(5):43-44
54 曹宏先. 黄芪注射液治疗冠心病 80 例临床分析. 中医药, 1997,(5):15
55 胡元会, 车维新, 曹贵民, 等. 心复康口服液对大鼠实验心衰模型心肌 Ca2+定位及 Ca2+-ATPase 活性的影响. 中国中医学基础杂志, 1999,5(10):27-30
56 曹雪滨, 李培建, 黄河玲, 等. 心复康口服液对大鼠实验性心肌性心肌缺血的保护作用. 中国药科大学学报, 1998,29(Suppl):196-198
57 宋春宇, 毕会民. 葛根素对大鼠胰岛素刺激下骨骼肌细胞 膜 GLUT4 蛋 白 含 量 的 影 响 . 中 国 中 药 杂志,2004,2:172 -175
58 李娟娟, 毕会民. 葛根素对胰岛素抵抗大鼠脂肪细胞葡萄糖转运蛋白 4 的影响. 中国临床药理学与治疗学, 2004,9(8):885-888
59 张雷, 陈立梅, 倪红霞. 葛根素影响链脲佐菌素诱导糖尿病大鼠脂肪细胞葡萄糖转运蛋白 4 的表达. 中国临床康复. 2006,39:135-138
60 Guang CH, Fu-er LU, Dan J. Effect of Huanglian Jiedu Skeletal Muscle Tissues of Insulin Resistant Rats. Chin J Integr Med, 2007Mar,13(1):41-45
61 毛先睛, 欧阳静萍, 吴勇. 中药黄芪多糖对糖尿病大鼠心肌GLUT4表达的影响. 武汉大学学报(医学版), 26(4): 457-459
62 陈立梅, 王尔孚. 汉防己甲素影响糖尿病大鼠各组织葡萄糖转运蛋白 4 蛋白表达的意义. 中国临床康复, 2006, 19:86-88
63 王彬, 王宗仁, 李军昌, 等. 芪丹通脉片对大鼠缺血/再灌注损伤心肌细胞GLUT4的影响.心脏杂志, 2007,19(3): 255-257
1 Mueckler M. Family of glucose-transporter genes, Implica- tions for glucose homeostasis and diabetes. Diabetes, 1990, 39:6-11
2 Wood IS, Trayhurn P. Glucose transporters (GLUT and SG- LT):expanded families of sugar transport proteins. Br J Nutr, 2003,89:3-9
3 Joost HG, Thorens B. The extended GLUT-family of sugar/ polyol transport facilitators:nomenclature,sequence charac- teristics, and potential function of its novel members. Mol Membr Biol, 2001,18(4):247-256
4 Santalucia T, Camps M, Castello A, et al. Developmental regulation of GLUT-1 (erythroid/Hep G2) and GLUT-4 (muscle/fat) glucose transporter expression in rat heart, skeletal muscle, and brown adipose tissue. Endocrinology, 1992,130:837-846
5 Katz EB, Burcelin R, Tsao TS, et al. The metabolic cones-quences of altered glucose transporter expression in trans- genic mice . Mol Med, 1996,74:639-652
6 Li SH, McNeilj H. In vivo effects of vanadium on GLUT4 translocation in cardiac tissue of STZ-diabetic rats. Molec- ular and Biochemistry, 2001,217:127-132
7 Rea S, James DE. Moving GLUT4: the biogenesis and traf- ficking of GLUT4 storage vesicles. Diabetes, 1997,46: 1667-1677
8 Li D, Randhawa VK, Patel N, et al. Hyperosmolarity redu- ces GLUT4 endocytosis and increases its exocytosis from a VAMP2-independent pool in l6 muscle cells. Biol Chem, 2001,276:22883-22891
9 Bryant NJ, Govers R, James DE. Regulated transport of the glucose transporter GLUT4. Cell Biol, 2002,3:267-277
10 James DE, Strube M, Mueckler M. Molecular cloning and characterization of an insulin-regulatable glucose transpo- rter. Nature, 1989,338:83-87
11 Carte E, Gregor YD, Andre G. Stimulation of glucose trans- port in skeletal muscle by hypoxia. Appl Physiol. 1991,70 (4):1593-1600
12 Lawrence H. Young MD, Yin R, et al. Low-Flow Ischem- ia Leads to Translocation of Canine Heart GLUT-4 and G- LUT-1 Glucose Transporters to the Sarcolemma In Vivo. Circulation, 1997,95:415-422
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