白芍总甙对大鼠腹腔巨噬细胞产生肿瘤坏死因子的调节机制  

Regulatory mechanism of total glucosides of paeony on tumor necrosis factor production by peritoneal macrophages in rats

作　　者：王斌[1,2] 陈敏珠[1,2] 徐叔云[1,2] 

机构地区：[1]安徽医科大学临床药理研究所 [2]安徽医科大学

出　　处：《中国药理学通报》1997年第3期255-257,共3页Chinese Pharmacological Bulletin

摘　　要：目的：研究不同浓度白芍总甙（ＴＧＰ）调节大鼠腹腔巨噬细胞（ＭΦ）产生肿瘤坏死因子（ＴＮＦ）作用。方法：在ＭΦ培养系统中有或无环氧酶抑制剂和钙调蛋白抑制剂等工具药，测定４５Ｃａ内流、ＰＧＥ２和ＴＮＦ含量。结果：ＴＧＰ（０．５～１０ｍｇ·Ｌ－１）明显促进ＬＰＳ诱导ＭΦ的４５Ｃａ内流和ＴＮＦ产生。线性回归分析表明，４５Ｃａ内流和ＴＮＦ产生呈明显正相关。三氟拉嗪（４０μｍｏｌ·Ｌ－１）可阻断ＴＧＰ促进ＬＰＳ诱导ＭΦ产生ＴＮＦ。ＴＧＰ－ＬＰＳ的ＴＮＦ释放曲线呈钟罩形，而ＴＧＰ－ＬＰＳ的ＰＧＥ２产生曲线呈浓度依赖性升高。当ＴＧＰ在低浓度（０．５～１２．５ｍｇ·Ｌ－１）时，ＴＮＦ与ＰＧＥ２产生明显正相关，而高浓度（１２．５～２５０ｍｇ·Ｌ－１）两者呈明显负相关。吲哚美辛（１０μｍｏｌ·Ｌ－１）可使ＴＮＦ量效曲线下降支消失，而Ｎω亚硝基－Ｌ－精氨酸（１５μｍｏｌ·Ｌ－１）对此无明显影响。结论：低浓度ＴＧＰ对ＴＮＦ产生上调作用可能与促进４５Ｃａ内流，提高钙调蛋白活性从而促进ＰＧＥ２分泌等有关，而高浓度下调作用是可能与ＭΦ自身产生大量ＰＧＥ２介导有关。AIM: To determine different concentrations of total glucosides of paeony(TGP) regulating tumor necrosis factor(TNF) production by peritoneal macophages(MΦ) in rats. METHODS: 45 Ca influx, the amount of prostaglandin E 2(PGE 2) and TNF in MΦ media were measured in the presence or absence of the inhibitors of cycloxygenase and calmodulin and other tool drugs. RESULTS: TGP(0 5￣10 mg·L -1 ) markedly increased both 45 Ca influx and TNF production in MΦ induced by lipopolysaccharide(LPS,5 mg·L -1 ). Linear regression analysis demonstrated a positive correlation between 45 Ca influx and TNF production. Trifluoperazine(40 μmol·L -1 ) could block the enhancing TNF production in TGP LPS activated MΦ cultures. The concentration effect curve of TGP LPS for TNF release seemed to be bell shaped, but that for PGE 2 secretion was enhanced in a concentration related way. There was a significant positive correlation between TNF and PGE 2 production when TGP in lower concentrations(0 5￣12 5 mg·L -1 ), but a negative correlation when TGP in higher ones(12 5￣250 mg·L -1 ). The descending limb of the curve of TNF was disappeared when indomethacin(10 μmol·L -1 ) was added, while its curve did not change when added Nω nitro L arginine(15 μmol·L -1 ). CONCLUSIONS: Up regulation of lower concentrations of TGP on TNF production may be associated with increasing 45 Ca influx and activating the calmodulin activity and then enhancing PGE 2 production, and down regulation of higher concentrations may be mediated through the excess PGE 2 production by MΦ itself.

关 键 词：白芍总甙 免疫调节 肿瘤坏死因子 巨噬细胞 

分 类 号：R979.5[医药卫生—药品] R967[医药卫生—药学]