Sun Yun-guang, Zhou Zhi-jun, Zhang Xue-mei, Gu Xi-an, Jin Tai-yi
School of Public Health, Fudan University, Shanghai 200032, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2004 Feb;22(1):7-10.
To study the tolerance of rats induced by 28 day pretreatment with low dosage of dimthoate and the toxic effects challenged by higher dosage of dimethoate, and to investigate the change of M receptor and the mechanism of tolerance formation.
SD rats were given 25 mg/kg dimethoate daily(sc) while control group was given saline daily instead for 28 days. The activity of whole blood acetylcholinesterase (AChE) was examined. On the 29th day three groups of administrated rats were challenged by saline solution, 50 mg/kg and 100 mg/kg dimethoate, respectively. The density and mRNA level of brain M(1), M(2) receptor were determined. Lymphocytes of peripheral blood were isolated, and basal, inducible M(3) gene expression were measured by RT-PCR.
During pretreatment, blood AChE activity decreased continually, it reached the lowest on the 13th day. And it decreased more after exposed to higher dosage of dimethoate. Brain AChE activity in the pretreated groups was lower than that in control group and decreased with the increase in challenging dosage. The density of M(1) receptor in negative control, pretreated, and 50, 100 mg/kg challenging groups were 979.15, 856.54, 539.46, 539.14 fmol/mg pro respectively. The change in relative levels of mRNA of M(1) receptor (2.59, 2.47, 2.20, 1.81) were consistent with the density of receptor but the level declined continually as the challenging dosage increased. The density of M(2) receptor were 507.38, 611.11, 548.42, 337.47 fmol/mg pro respectively, which were not obviously affected by pretreatment but decreased as the challenging dosage increased. The change in levels of M(2) receptor mRNA was not obvious. The basal gene expression of M(3) receptor mRNA was not different among all experimental groups while the inducible gene expression decreased with the increase in challenging dosage.
Low level dosage of dimethoate could induce animals to tolerate dimethoate toxicity. Reduction of M(1) receptor density which may be induced by the decrease in its gene expression may be the mechanism of tolerance. The change of M(3) receptor mRNA inducible expression in lymphocyte accorded with M(1) receptor mRNA expression in the brain.
研究低剂量乐果预处理28天对大鼠的耐受性及高剂量乐果攻击后的毒性作用，探讨M受体变化及耐受性形成机制。
SD大鼠每日皮下注射25mg/kg乐果，对照组每日注射生理盐水，连续28天。检测全血乙酰胆碱酯酶（AChE）活性。第29天，将三组给药大鼠分别用生理盐水、50mg/kg和100mg/kg乐果进行攻击。测定脑M(1)、M(2)受体密度及mRNA水平。分离外周血淋巴细胞，用RT-PCR检测基础及诱导型M(3)基因表达。
预处理期间，血AChE活性持续下降，第13天降至最低。高剂量乐果暴露后下降更明显。预处理组脑AChE活性低于对照组，且随攻击剂量增加而降低。阴性对照组、预处理组及50、100mg/kg攻击组M(1)受体密度分别为979.15、856.54、539.46、539.14fmol/mg蛋白。M(1)受体mRNA相对水平变化（2.59、2.47、2.20、1.81）与受体密度一致，但随攻击剂量增加水平持续下降。M(2)受体密度分别为507.38、611,11、548.42、337.47fmol/mg蛋白，预处理对其影响不明显，但随攻击剂量增加而降低。M(2)受体mRNA水平变化不明显。各实验组M(3)受体mRNA基础基因表达无差异，诱导基因表达随攻击剂量增加而降低。
低剂量乐果可诱导动物对乐果毒性产生耐受性。M(1)受体密度降低可能是其基因表达下降所致，可能为耐受性形成机制。淋巴细胞中M(3)受体mRNA诱导表达变化与脑内M(1)受体mRNA表达一致。
