粉防己碱对高血压大鼠血管平滑肌细胞增殖的抑制作用
李庆平 陆泽安 饶曼人
摘 要：探讨了粉防己碱(Tet)抑制培养的大鼠主动脉平滑肌细胞(AVSMC)增殖的作用，MTT法分析细胞增殖，[3H]TdR参入法分析细胞DNA合成.结果显示：①肾血管性高血压〔RH，二肾一夹(2K1C)术后18周〕大鼠AVSMC超微结构呈典型的合成细胞特征;②RH大鼠AVSMC具有更活跃的增殖倾向,血管紧张素Ⅱ(AngⅡ)和去甲肾上腺素(NE)刺激下指数增长期细胞数和在NE刺激下的AVSMC生长率均明显增高；③Tet(50mg.kg-1.d-1，po，2K1C术后9周始，连续9周)治疗组的AVSMC对NE和AngⅡ诱导的细胞增殖反应性和生长率较RH组明显降低；④对RH组和伪手术组大鼠的AVSMC，Tet(0.1～10μmol.L-1)体外给药可浓度依赖性地抑制NE或AngⅡ诱导的增殖和[3H]TdR参入.研究表明，RH大鼠AVSMC对NE和AngⅡ促增殖作用敏感性及反应性增高；Tet可降低其对NE和AngⅡ的反应性，抑制AVSMC增殖和DNA合成.
, http://www.100md.com
关键词：粉防己碱;高血压,肾血管性;肌,平滑,血管;细胞,培养的;细胞增殖
分类号：R972.4 文献标识码：A
文章编号：1000-3002(2001)02-0145-05
Depressive effect on proliferation of vascular smooth muscle cells by tetrandrine in hypertensive rats
LI Qing-Ping(Department of Cardiovascular Pharmacology, Nanjing Medical University, Nanjing 210029, China)
LU Ze-An(Department of Cardiovascular Pharmacology, Nanjing Medical University, Nanjing 210029, China)
, http://www.100md.com
RAO Man-Ren(Department of Cardiovascular Pharmacology, Nanjing Medical University, Nanjing 210029, China)
Abstract：To analyse the effect of tetrandrine(Tet) on proliferation of aortic vascular smooth muscle cells ( AVSMC), AVSMC were isolated and cultured from sham-operated rats(Sham), renovascular hypertensive rats〔RHR, 18 weeks after two kidney one clip(2K1C) operation〕, and Tet (50 mg.kg-1.d-1 po for 9 weeks from week 9 after 2K1C operation)treated RHR. The proliferation of AVSMC was detected by MTT method, and the DNA synthesis was evaluated by [3H]-thymidine incorporation. The results showed that ①The ultrastructure of aorta suggested that AVSMC in RHR had transferred from contractile phenotype to synthetic phenotype; ②Compared to Sham, AVSMC from RHR showed a higher proliferative property with a higher cell number and an increased growth rate stimulated by norepinephrine(NE) or angiotensinⅡ(AngⅡ); ③Compared to untreated RHR, AVSMC from Tet treated RHR showed a reduced reactivity to NE- or AngⅡ-stimulated proliferation and growth rate; ④Tet(0.1-10 μmol.L-1) treated in vitro induced a concentration-dependent depression in [3H] thymidine-incorporation stimulated by NE or AngⅡ in AVSMC from either RHR or Sham. This study provides an evidence of increased reactivity to NE or AngⅡ in AVSMC of RHR. Tet inhibits the proliferation and DNA synthesis in AVSMC, depresses the susceptibility of AVSMC to AngⅡ and NE, both contribute to the regression effect on hypertensive vascular remodeling.
, http://www.100md.com
Keywords：tetrandrine; hypertension, renovascular; muscle, smooth, vascular; cells, cultured; cell proliferation
基金项目：江苏省自然科学基金(BK97049)
作者简介：李庆平(1954-)，女，安徽合肥人，博士，副教授，主要研究方向心血管药理学. 联系作者. Tel: (025)6662883, Fax: (025)6508960, E-mail: qpli@njmu.edu.cn
作者单位：李庆平(南京医科大学心血管药理学研究室, 江苏南京 210029)
陆泽安(南京医科大学心血管药理学研究室, 江苏南京 210029)
饶曼人(南京医科大学心血管药理学研究室, 江苏南京 210029)
, http://www.100md.com
参考文献：
[1]徐毅, 周承愉, 李云霞. 粉防己碱对血管紧张素Ⅱ促进心肌成纤维细胞增殖的抑制作用[J]. 中国应用生理学杂志, 1996, 12(3):198-202.
[2]Reist RH, Dey RD, Durham JP, Rojanasakul Y, Castranova V. Inhibition of proliferative activity of pulmonary fibroblasts by tetrandrine[J]. Toxicol Appl Pharmacol, 1993, 122(1):70-76.
[3]He QY, Zhou WD, Ji L, Zhang HQ, He NG, Xue SB. Characteristics of harringtonine-resistant human leukemia HL 60 cell[J]. Acta Pharmacol Sin, 1996, 17(5):463-467.
, 百拇医药
[4]司徒镇强, 吴军正. 细胞培养[M]. 西安:世界图书出版社, 1996. 186-187.
[5]Hadrava V, Tremblay J, Hamet P. Abnormalities in growth characteristics of aortic smooth muscle cells in spontaneously hypertensive rats[J]. Hypertension, 1989, 13(6 Pt 1):589-597.
[6]Schiffrin EL. Remodeling of resistance arteries in human hypertension: effects of cilazapril, an angiotensin-Ⅰ-converting enzyme inhibitor[J]. Cardiology, 1995, 86(Suppl 1):16-22.
, http://www.100md.com
[7]Fukuda N, Hu WY, Satoh C, Nakayama M, Kishioka H, Kubo A, et al. Contribution of synthetic phenotype on the enhanced angiotensin Ⅱ-generating system in vascular smooth muscle cells from spontaneously hypertensive rats[J]. J Hypertens, 1999, 17(8):1099-1107.
[8]Blaes N, Boissel JP. Growth-stimulating effect of catecho- lamines on rat aortic smooth muscle cells in culture[J]. J Cell Physiol, 1983, 116(2):167-172.
[9]Berk BC, Vekshtein V, Gordon HM, Tsuda T. AngiotensinⅡ-stimulated protein synthesis in cultured vascular smooth muscle cells[J]. Hypertension, 1989, 13(4):305-314.
, http://www.100md.com
[10]Liu QY, Karpinski E, Pang PK. Tetrandrine inhibits both T and L calcium channel currents in ventricular cells[J]. J Cardiovasc Pharmacol, 1992, 20(4):513-519.
[11]Hermsmeyer K, Mishra S, Miyagawa K, Minshall R. Physiologic and pathophysiologic relevance of T-type calcium-ion channels: potential indications for T-type calcium antagonists[J]. Clin Ther, 1997, 19(Suppl A):18-26., 百拇医药
摘 要：探讨了粉防己碱(Tet)抑制培养的大鼠主动脉平滑肌细胞(AVSMC)增殖的作用，MTT法分析细胞增殖，[3H]TdR参入法分析细胞DNA合成.结果显示：①肾血管性高血压〔RH，二肾一夹(2K1C)术后18周〕大鼠AVSMC超微结构呈典型的合成细胞特征;②RH大鼠AVSMC具有更活跃的增殖倾向,血管紧张素Ⅱ(AngⅡ)和去甲肾上腺素(NE)刺激下指数增长期细胞数和在NE刺激下的AVSMC生长率均明显增高；③Tet(50mg.kg-1.d-1，po，2K1C术后9周始，连续9周)治疗组的AVSMC对NE和AngⅡ诱导的细胞增殖反应性和生长率较RH组明显降低；④对RH组和伪手术组大鼠的AVSMC，Tet(0.1～10μmol.L-1)体外给药可浓度依赖性地抑制NE或AngⅡ诱导的增殖和[3H]TdR参入.研究表明，RH大鼠AVSMC对NE和AngⅡ促增殖作用敏感性及反应性增高；Tet可降低其对NE和AngⅡ的反应性，抑制AVSMC增殖和DNA合成.
, http://www.100md.com
关键词：粉防己碱;高血压,肾血管性;肌,平滑,血管;细胞,培养的;细胞增殖
分类号：R972.4 文献标识码：A
文章编号：1000-3002(2001)02-0145-05
Depressive effect on proliferation of vascular smooth muscle cells by tetrandrine in hypertensive rats
LI Qing-Ping(Department of Cardiovascular Pharmacology, Nanjing Medical University, Nanjing 210029, China)
LU Ze-An(Department of Cardiovascular Pharmacology, Nanjing Medical University, Nanjing 210029, China)
, http://www.100md.com
RAO Man-Ren(Department of Cardiovascular Pharmacology, Nanjing Medical University, Nanjing 210029, China)
Abstract：To analyse the effect of tetrandrine(Tet) on proliferation of aortic vascular smooth muscle cells ( AVSMC), AVSMC were isolated and cultured from sham-operated rats(Sham), renovascular hypertensive rats〔RHR, 18 weeks after two kidney one clip(2K1C) operation〕, and Tet (50 mg.kg-1.d-1 po for 9 weeks from week 9 after 2K1C operation)treated RHR. The proliferation of AVSMC was detected by MTT method, and the DNA synthesis was evaluated by [3H]-thymidine incorporation. The results showed that ①The ultrastructure of aorta suggested that AVSMC in RHR had transferred from contractile phenotype to synthetic phenotype; ②Compared to Sham, AVSMC from RHR showed a higher proliferative property with a higher cell number and an increased growth rate stimulated by norepinephrine(NE) or angiotensinⅡ(AngⅡ); ③Compared to untreated RHR, AVSMC from Tet treated RHR showed a reduced reactivity to NE- or AngⅡ-stimulated proliferation and growth rate; ④Tet(0.1-10 μmol.L-1) treated in vitro induced a concentration-dependent depression in [3H] thymidine-incorporation stimulated by NE or AngⅡ in AVSMC from either RHR or Sham. This study provides an evidence of increased reactivity to NE or AngⅡ in AVSMC of RHR. Tet inhibits the proliferation and DNA synthesis in AVSMC, depresses the susceptibility of AVSMC to AngⅡ and NE, both contribute to the regression effect on hypertensive vascular remodeling.
, http://www.100md.com
Keywords：tetrandrine; hypertension, renovascular; muscle, smooth, vascular; cells, cultured; cell proliferation
基金项目：江苏省自然科学基金(BK97049)
作者简介：李庆平(1954-)，女，安徽合肥人，博士，副教授，主要研究方向心血管药理学. 联系作者. Tel: (025)6662883, Fax: (025)6508960, E-mail: qpli@njmu.edu.cn
作者单位：李庆平(南京医科大学心血管药理学研究室, 江苏南京 210029)
陆泽安(南京医科大学心血管药理学研究室, 江苏南京 210029)
饶曼人(南京医科大学心血管药理学研究室, 江苏南京 210029)
, http://www.100md.com
参考文献：
[1]徐毅, 周承愉, 李云霞. 粉防己碱对血管紧张素Ⅱ促进心肌成纤维细胞增殖的抑制作用[J]. 中国应用生理学杂志, 1996, 12(3):198-202.
[2]Reist RH, Dey RD, Durham JP, Rojanasakul Y, Castranova V. Inhibition of proliferative activity of pulmonary fibroblasts by tetrandrine[J]. Toxicol Appl Pharmacol, 1993, 122(1):70-76.
[3]He QY, Zhou WD, Ji L, Zhang HQ, He NG, Xue SB. Characteristics of harringtonine-resistant human leukemia HL 60 cell[J]. Acta Pharmacol Sin, 1996, 17(5):463-467.
, 百拇医药
[4]司徒镇强, 吴军正. 细胞培养[M]. 西安:世界图书出版社, 1996. 186-187.
[5]Hadrava V, Tremblay J, Hamet P. Abnormalities in growth characteristics of aortic smooth muscle cells in spontaneously hypertensive rats[J]. Hypertension, 1989, 13(6 Pt 1):589-597.
[6]Schiffrin EL. Remodeling of resistance arteries in human hypertension: effects of cilazapril, an angiotensin-Ⅰ-converting enzyme inhibitor[J]. Cardiology, 1995, 86(Suppl 1):16-22.
, http://www.100md.com
[7]Fukuda N, Hu WY, Satoh C, Nakayama M, Kishioka H, Kubo A, et al. Contribution of synthetic phenotype on the enhanced angiotensin Ⅱ-generating system in vascular smooth muscle cells from spontaneously hypertensive rats[J]. J Hypertens, 1999, 17(8):1099-1107.
[8]Blaes N, Boissel JP. Growth-stimulating effect of catecho- lamines on rat aortic smooth muscle cells in culture[J]. J Cell Physiol, 1983, 116(2):167-172.
[9]Berk BC, Vekshtein V, Gordon HM, Tsuda T. AngiotensinⅡ-stimulated protein synthesis in cultured vascular smooth muscle cells[J]. Hypertension, 1989, 13(4):305-314.
, http://www.100md.com
[10]Liu QY, Karpinski E, Pang PK. Tetrandrine inhibits both T and L calcium channel currents in ventricular cells[J]. J Cardiovasc Pharmacol, 1992, 20(4):513-519.
[11]Hermsmeyer K, Mishra S, Miyagawa K, Minshall R. Physiologic and pathophysiologic relevance of T-type calcium-ion channels: potential indications for T-type calcium antagonists[J]. Clin Ther, 1997, 19(Suppl A):18-26., 百拇医药
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