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

THE INHIBITORY EFFECT OF TETRANDRINE ON ANGIOTENSIN Ⅱ STIMULATED PROLIFERATION IN CULTURED NEONATAL RAT CARDIAC FIBROBLASTS

血管紧张素（ＡＮＧ）Ⅱ对新生大鼠无血清培养第二代心肌成纤维细胞（ＦＢ）具有剂量依赖性的促进增殖、ＤＮＡ和ＲＮＡ以及胶原合成的作用。ＡＮＧⅡ１０７ｍｏｌ／Ｌ浓度时，ＦＢ的［３Ｈ］胸腺嘧啶核苷（Ｔｈｙｍｉｄｉｎｅ），［３Ｈ］尿嘧啶核苷（Ｕｒｉｄｉｎｅ），［３Ｈ］脯氨酸（Ｐｒｏｌｉｎｅ）掺入较对照组分别增加１６７％，５８％，１７４％，此刺激作用可被特异性ＡＮＧⅡ受体拮抗剂阻断；粉防己碱预处理也可抑制ＡＮＧⅡ上述作用，且呈剂量依赖性。以上结果提示：ＡＮＧⅡ通过受体介导直接刺激心肌ＦＢ增殖和胶原合成，引起心肌纤维化；钙拮抗剂粉防己碱对ＡＮＧⅡ导致的心肌纤维化具有抑制作用。

Withangiotensin Ⅱ(ANGⅡ, 10 10 -10 5 mol/L), a dose dependent augmentation of proliferation, DNA, RNA and collagen synthesis in serum free cultured passageⅡneonatal rat cardiac fibroblasts (FB) was observed. Treatment of FB with 10 7 mol/L ANGⅡ for 24h caused a significant increase in thymidine, uridine, proline incorporation by 167%, 58%, 174%respectively, while these stimulatory effects were completely inhibited by specifc ANGⅡ receptor antagonist,[Sar 1,Thr 8]ANGⅡ(10 5 mol/L). Pretreatment of tetrandrine (Tet)in various concentrations(10 10 10 5 mol/L)could also block stimulatory effects of ANGⅡ. These data suggest that the proliferation and collagen synthesis in cardiac FB induced by ANGⅡ may be mediated by ANGⅡ receptor, and these stimulatory effects can be inhibited by the calcium channel blocker tetrandrine.