粉防己堿對(duì)高血壓大鼠血管平滑肌細(xì)胞增殖的抑制作用

摘　要：探討了粉防己堿（Tet）抑制培養(yǎng)的大鼠主動(dòng)脈平滑肌細(xì)胞（AVSMC）增殖的作用，MTT法分析細(xì)胞增殖，［3H］TdR參入法分析細(xì)胞DNA合成.結(jié)果顯示：①腎血管性高血壓〔RH，二腎一夾（2K1C）術(shù)后18周〕大鼠AVSMC超微結(jié)構(gòu)呈典型的合成細(xì)胞特征;②RH大鼠AVSMC具有更活躍的增殖傾向,血管緊張素Ⅱ(AngⅡ)和去甲腎上腺素(NE)刺激下指數(shù)增長期細(xì)胞數(shù)和在NE刺激下的AVSMC生長率均明顯增高；③Tet（50mg.kg-1.d-1，po，2K1C術(shù)后9周始，連續(xù)9周）治療組的AVSMC對(duì)NE和AngⅡ誘導(dǎo)的細(xì)胞增殖反應(yīng)性和生長率較RH組明顯降低；④對(duì)RH組和偽手術(shù)組大鼠的AVSMC，Tet（0.1～10μmol.L-1）體外給藥可濃度依賴性地抑制NE或AngⅡ誘導(dǎo)的增殖和［3H］TdR參入.研究表明，RH大鼠AVSMC對(duì)NE和AngⅡ促增殖作用敏感性及反應(yīng)性增高；Tet可降低其對(duì)NE和AngⅡ的反應(yīng)性，抑制AVSMC增殖和DNA合成.
關(guān)鍵詞：粉防己堿;高血壓,腎血管性;肌,平滑,血管;細(xì)胞,培養(yǎng)的;細(xì)胞增殖

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）　
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.
Keywords：tetrandrine; hypertension, renovascular; muscle, smooth, vascular; cells, cultured; cell proliferation
參考文獻(xiàn)：
［1］徐毅, 周承愉, 李云霞. 粉防己堿對(duì)血管緊張素Ⅱ促進(jìn)心肌成纖維細(xì)胞增殖的抑制作用[J]. 中國應(yīng)用生理學(xué)雜志, 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.