阿片类物质对猴免疫缺陷病毒感染的CEM×174细胞内p53合成的调节作用(英文)

Regulation of Opiates on the Synthesis of Intracellular Protein p53 in CEM ×174 cells Infected with Simian Immunodeficiency Virus

已经证明阿片类物质如吗啡能够刺激猴免疫缺陷病毒 ( SIV)的复制 ,并最终加速细胞死亡 ,但是其机理却研究很少 .为探讨吗啡和甲硫氨酸脑啡肽对细胞内 p53合成的作用 ,用 SIV感染CEM× 1 74细胞 ,同时分析 SIV感染时病理过程的机理 .在 CEM× 1 74细胞感染 SIV后不同时间 ,p53含量逐渐增加 ,但 1 0 -7mol/L的吗啡仅在起始阶段对其有促进作用 .在 SIV感染组加入吗啡或甲硫氨酸脑啡肽进行时间曲线实验时 ,p53含量较低 .加入 1 0 -8～ 1 0 -6mol/L吗啡 8h,正常细胞 p53含量仅有轻微改变 .但在 SIV感染情况下 ,则呈现剂量依赖性的大量增加 .相反 ,1 0 -8- 1 0 -6mol/L甲硫氨酸脑啡肽在 8h时能增加正常细胞 p53合成达 60 % .在 SIV感染时 ,SIV本身能够促进 p53的含量 .尽管各组 p53仍然高于对照组 ,但甲硫氨酸脑啡肽对其不再起作用 .结果提示甲硫氨酸脑啡肽对正常细胞 p53含量有明显影响 ,而吗啡 8h增加 SIV感染细胞的 p53含量可能是其加速爱滋病病理过程的机理之一 .

It has been recently proved that opioids,such as morphine,can stimulate simian immunodeficiency virus(SIV) replication and accelerate cell death eventually,but the mechanisms involved were seldom investigated.In order to investigate the effects of morphine sulfate and methionine enkephalin on the synthesis of intracellular protein p53,CEM ×174 cells were infected with SIV and the mechanisms of the associated pathogenesis in SIV infection were thereby assessed.The results showed that a progressive increase of p53 content could be observed after CEM ×174 cells were infected with SIV for a different period of time,but a promoted effect of morphine sulfate at 10 -7 mol/L could be seen only at the initial stage.Lower contents of p53 were observed in 72 hours treatment with SIV and morphine sulfate or methionine enkephalin.Morphine sulfate at concentrations of 10 -8 -10 -6 mol/L after 8 hours treatment could only slightly change the content of p53 protein in the normal cells and the change was greatly enlarged by SIV infection in a dose dependent manner.In contrast,methionine enkephalin could upregulate the synthesis of p53 protein in normal cells by up to 60% at the concentration of 10 -8 -10 -6 mol/L after 8 hours treatment.In the case of SIV infection,it was observed that SIV per se could enhance the content of p53,but the effects of methionine enkephalin were reversed even though it was still higher than control.The results indicate that methionine enkephalin may obviously influence the content of p53 on the normal cells whereas the elevated p53 content by morphine in SIV infected cells for 8 hours incubation may be one of the mechanisms that morphine could accelerate the rate of progression to AIDS.