索曼染毒对大鼠脑组织乙酰胆碱受体m1和m4 mRNA表达的影响

Changes of the expressions of m1,m4 mRNA of brain in rats treated with low-dose soman

目的研究慢性小剂量索曼(soman)染毒对大鼠海马和前额叶皮层乙酰胆碱受体m1和m4 mRNA表达的影响。方法以皮下注射索曼为大鼠染毒模型,雄性健康Wistar大鼠随机分为6μg/kg染毒组(6μg/kg)、10μg/kg染毒组(10μg/kg)、生理盐水对照组(相同体积的生理盐水),半数致死量对照组(大鼠在取样前注射一次索曼,剂量为100μg/kg),每组6只;除半数致死量染毒对照组外,均每日上午背部注射1次,共14 d。采用RT-PCR方法检测大鼠海马和前额叶皮层乙酰胆碱受体m1和m4 mRNA表达水平。结果乙酰胆碱受体m1和m4 mRNA的变化结果以OD乙酰胆碱受体m1(乙酰胆碱受体m4)/ODGAPDH表示,6μg/kg组大鼠前额叶皮层乙酰胆碱受体m1 mRNA为(0.250±0.016),10μg/kg组为(0.247±0.018),均显著低于生理盐水对照组(0.287±0.021)和半数致死量对照组(0.277±0.028)(P<0.05);海马乙酰胆碱受体m1 mRNA表达无明显变化(P>0.05),6μg/kg组为(0.275±0.022),10μg/kg组为(0.270±0.019),生理盐水对照组为(0.294±0.027),半数致死量对照组为(0.289±0.029)。6μg/kg组和10μg/kg组前额叶皮层乙酰胆碱受体m4 mRNA表达分别为(0.364±0.031)和(0.426±0.066),均显著高于生理盐水对照组(0.274±0.025)和半数致死量对照组(0.271±0.046)(P<0.01),6μg/kg组和10μg/kg组海马乙酰胆碱受体m4 mRNA表达分别为(0.627±0.030)和(0.671±0.074),均显著高于生理盐水对照组(0.528±0.031)和半数致死量对照组(0.531±0.054)(P<0.01)。在生理盐水对照组和半数致死量对照组间乙酰胆碱受体m1 mRNA和m4 mRNA表达水平均无显著差别(P>0.05)。结论小剂量索曼染毒致大鼠前额叶皮层乙酰胆碱受体m1mRNA表达下降,海马和前额叶皮层乙酰胆碱受体m4 mRNA表达增加,这种变化为索曼慢性作用的结果。索曼可能从基因水平影响乙酰胆碱M受体的表达,从而导致胆碱能系统功能下降及大鼠学习记忆障碍。

Objective To observe the expressions of m1 m4 mRNA in the brain of rats chronically treated with low-dose soman. Methods Twenty-four male Wistar rats were randomly divided into 6 μg/kg soman （6 μg/kg soman was injected subcutaneously for 14 d）, 10 μg/kg soman （10 μg/kg soman was injected subcutaneously for 14 d）, normal saline control （saline was injected subcutaneously for 14 d） , and 100 μg/kg median lethal dose control groups, （100 μg/kg soman was injected subcutaneously once before sampling）. RT-PCR was carried out to investigate the expressions of m1, m4 mRNA in the brain of rats on the next day after received the last injection. Results The expression of m1 in the prefrontal cortex was significantly decreased in rats injected of soman for 14 d. No significant change of the ex- pression of ml mRNA in the hippocampus was found. While the expressions of m4 mRNA both in prefrontal cortex and the hippocampus were increased significantly. The expressions of m1 and m4 mRNA in the brain had no significant changes between median lethal dose control group control and normal saline control group. Conclusions Soman may influence the expression of M-receptor from gene level and inhibit learning and memory via disordering the function of central cholinergic system.