P53、P21^(WAF/CIP1)和Cyclin D1基因蛋白在沥青烟暴露小鼠肺组织中的表达

The Expressions of P53,P21^(WAF/CIP1) and Cyclin D1 in Lung Tissue of Mice Treated with Bitumen Fume

[目的]探讨沥青烟对小鼠肺组织形态及基因蛋白P53、P21^(WAF/CIP1)和Cyclin D1表达的影响。[方法]建立沥青烟亚急性染毒小鼠模型,将120只昆明种健康小鼠随机分为3组,即1个对照组和2个染毒组,染毒组进行不同浓度(55、165mg/m^3)和不同时间(30、60d)染毒,光镜下观察肺组织形态改变,采用免疫组化S-P法,对P53、P21、Cyclin D1染色,观察P53、P21和Cyclin D1基因蛋白表达。[结果]不同浓度、不同时间染毒小鼠肺组织形态有不同程度改变,高浓度染毒组出现不典型增生。小鼠肺组织P53基因蛋白表现为低浓度染毒30d组,未见阳性表达;高浓度染毒60d组呈强阳性表达(P<0.01)。P21^(WAF/CIP1)基因蛋白表达低浓度染毒30d呈阳性表达;高浓度染毒60d组表达明显下调(P<0.01)。Cyclin D1基因蛋白表达同P53基因蛋白表达。[结论]随着染毒浓度和染毒时间的增加,肺组织增生逐渐明显,P53和Cyclin D1基因蛋白的表达呈上升趋势,P21^(WAF/CIP1)呈下降趋势。

[ Objective ] To observe the pathological morphology changes and the effects on the expressions of P53, P21^WAF/CIP1 and Cyclin D1 in mice lung tissue caused by bitumen fume. [ Methods ] In this subchronic toxicity study, 60 Kunming mice were randomly divided into control and experimental groups. The experimental groups were exposed to bitumen fumes in different dosage（ 55 mg/m^3 and 165 mg/m^3 ）and different times（ 30 days and 60 days ）by inhalation in a sealed vessel. Morphologic features of lung tissue were observed under optical microscope. The expressions of P53, P21^WAF/CIP1 and Cyclin D1 gene were observed by immuneohistochemical method. [ Results ] With the increase of bitumen fume dosage and the time of inhalation, the main pathological changes of bitumen fume-treated groups were atypical hyperplasia in different extent. The protein expression of P53 and Cyclin D1 were negative in the group of low dosage and 30 days but strong positive in the group of high dosage and 60 days（ P 〈 0.01 ）; the protein expression of P21 decreased significantly with the bitumen fume dosage and the time of inhalation increased（ P 〈 0.01 ）. [ Conclusions ] The hyperplasia in the lung tissue became more evident with the bitumen fume dosage and the time of inhalation. The protein expression of P53 and Cyclin D1 increased and the protein expression of P2^WAF/CIP1 decreased gradually.