四氢原小檗碱类药物对培养大鼠单个心肌细胞内游离Ca^（2＋）的影响

EFFECTS OF TETRAHYDROPROTOBERBERINES ON CYTOSOLIC FREE CALCIUM IN CULTURED RAT SINGLE MYOCARDIAL CELLS

用Ｆｕｒａ－２／ＡＭ技术和ＡＲ－ＣＭ－ＭＩＣ阳离子测定系统，直接测定了四氢小檗碱（ｔｅｔｒａｈｙ－ｄｒｏｂｅｒｂｅｒｉｎｅ，ＴＨＢ）、左旋四氢巴马汀（ｌ－ｔｅｔｒａｈｙｄｒｏｐａｌｍａｔｉｎｅ，ＴＨＰ）和左旋千金藤立定（ｌ－ｓｔｅｐｈｏｌｉｄｉｎｅ，ＳＰＯ）对培养大鼠单个心室肌细胞内游离钙（［Ｃａ１＋］ｉ）的影响，并与维拉帕米（Ｖｅｒ）做了比较。结果显示，ＴＨＢ，ＴＨＰ，ＳＰＤ浓度为１０～１００μｍｏｌ·Ｌ－１时，均可使静息［Ｃａ２＋］ｉ轻度升高，河豚毒素不能抑制之；浓度为１～１００μｍｏｌ·Ｌ－１时，可明显抑制高Ｋ＋引起的［Ｃａ２＋］ｉ增高；３０μｍｏｌ·Ｌ－１对胞外高Ｃａ２＋和去甲肾上腺素引起的［Ｃａ２＋］ｉ增高也有明显的抑制作用，但均较Ｖｅｒ的抑制作用为弱；ＴＨＰＢ对哇巴因引起的［ｃａ２＋］ｉ升高无明显抑制作用。结果提示，ＴＨＢ，ＴＨＰ，ＳＰＤ在抑制电压依赖性钙通道从而影响细胞膜［ｃａ２＋］ｉ内流方面与Ｖｅｒ相似，但比Ｖｅｒ弱。

Effect of tetrahydroberberine(THB),l-tetrahydropalmatine(THP) and l-stepholi-dine(SPD) were supposed to be related to the blocking of calcium influx. In this paper,using Fura-2/AM and AR- CM-MIC cation measurement system,the effects of THB,THP and SPD on cytosolicfree calcium([Ca2+]i) in cultured rat single myocardial cells were examined and compared withverapamil(Ver). TH,THP and SPD(10～100μ mol·L-1) were found to increase resting[Cas+]i gently,which was not depressed by tetrodotoxin. THB,THP and SPD(1～100μmol·L-1)were also shown to inhibit the KCl- induced[Ca2+]i elevation, the IC50 values of THBand SPD were 50.9(95%confidence limits: 18.5～140)μ mol·L-1 and 23.5(95%confidencelimits 7.6～73.4)μmol·L-1, respectively. THB, THP and SPD 30μmol·L-1 were also shown toinhibit the elevation of[Ca2+]i induced by high extracellular calcium and norepinephrine; but theinhibitory effects of these drugs were weaker than those of Ver. The three compounds showed nosignificant effect on ouabain induced[Ca2+]i increas1e. These results suggest that the inhibitory effects of THB, THP and SPD on [Ca2+]i in myocite by blocking voltage- dependent calcium channels were similar but inferior to Ver.