三聚氰胺对大鼠肾脏病理改变和凋亡基因表达水平的影响

Pathological analysis and mRNA expression of apoptosis genes in rat kidney tissue after subacute melamine treatment

目的 探讨三聚氰胺染毒大鼠肾脏的病理改变和凋亡基因bcl-2、bax和Caspase-3mRNA表达水平的变化.方法 用三聚氰胺对SD大鼠进行亚急性经口染毒,设1个对照组和3个实验组,每组雌雄大鼠各10只.雌雄大鼠分别进行染毒,雌性大鼠3组染毒剂量分别为150、300、600mg/kg,雄性大鼠3组染毒剂量分别为200、400、800 mg/kg.每天经口灌胃染毒1次,共28 d.实验结束时取大鼠肾脏组织进行病理学检查,并用荧光定量聚合酶链反应（PCR）检测肾组织凋亡基因bcl-2、bax和Caspase-3基因的mRNA表达水平.结果 低剂量组、中剂量组、高剂量组雌雄动物共发现11例、13例、16例肾小管透明管型.与对照组比较,各剂量组雄性大鼠和雌性大鼠bcl-2 mRNA表达水平下降20.58%～49.51%,bax升高44.66%～300.96%,Caspase-3升高64.76%～360.75%,差异均有统计学意义（P＜0.05或P＜0.01）.结论 三聚氰胺亚急性染毒可导致大鼠肾脏病理损害,引起肾组织凋亡基因表达水平发生改变.

Objective To investigate pathological changes and mRNA expression of apoptosis genes bcl-2, bax and Caspase-3 in rat kidney tissue after rats are administrated with melamine for 28 days. Methods 10 male SD rats and 10 female SD rats in each group were administrated with three doses of melamine （low dose, middle dose, high dose） by gavage for 28 days. The animals were divided into three experimental groups and one control group. The doses for male rats were 200, 400, 800 mg/kg, but for female rats they were 150,300, 600 mg/kg. After melamine treatment the animals were sacrificed and the kidneys were taken out for pathological analysis and for detecting mRNA expression of bcl-2, bax and Caspase-3 with fluorescent quantitative PCR assay. Results The tubular cylinders were observed in three experimental groups. The positive rates of tubular cylinders in three groups （from low dose to high dose） were 11/20, 13/20, 16/20, respectively.Additionally, melanine induced a significant decrease in mRNA expression of bcl-2 at low dose, middle dose or high dose, bcl-2 expression decreased by 20.58%-49.51% in three groups treated with melamine. Furthermore, bax mRNA levels increased by 44.66%-300.96% in groups treated with three doses of melamine, and Caspase-3 mRNA levels increased by 64.76%-360.75% in groups treated with three doses of melamine.Conclusions Melamine could induce pathological changes of rat kidneys, and it also induces a significant alteration of apoptosis Bcl-2,Bax and Caspase-3 mRNA expression in rat kidney tissue.