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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。
Objective: To study the effects of different concentrations of total glucosides of paeony (TGP) on tumor necrosis factor (TNF) production by peritoneal macrophages (MΦ) in rats. Methods: In the MΦ culture system with or without epoxidase inhibitor and calmodulin inhibitors and other tools to determine 45Ca influx, PGE2 and TNF levels. Results: TGP (0.5 ~ 10 mg · L-1) significantly promoted 45Ca influx and TNF production induced by LPS in MΦ. Linear regression analysis showed that 45Ca influx and TNF production was positively correlated. Trifluoperazine (40μmol·L-1) blocked TGP and promoted LPS-induced MΦ production of TNF. TGP-LPS TNF release curve bell-shaped, and TGP-LPS PGE2 production curve showed a concentration-dependent increase. When TGP was at a low concentration (0.5-12.5 mg · L -1), there was a significant positive correlation between TNF and PGE 2, while a significant negative correlation was observed between high concentrations (12.5-250 mg · L -1) of TGP. Indometacin (10μmol·L-1) decreased the decline of TNF dose-response curve, while Nω-N-L-arginine (15μmol·L-1) had no effect on this effect. CONCLUSION: Upregulation of TGP by low concentration of TGP may be related to the promotion of 45 Ca influx, increase of calmodulin activity, and promote the secretion of PGE2. However, the down-regulation of high concentration of TGP may be related to the large amount of PGE2 mediated by MΦ itself.