硫酸镍对大鼠垂体组织Caspase-3表达、激素和病理学影响

Effect of nickel sulfate on Caspase-3 expression,hormone and pathology in pituitary of rats

目的了解硫酸镍腹腔注射染毒对大鼠垂体功能和病理产生的损伤及凋亡蛋白Caspase-3表达的情况。方法健康雄性Wister大鼠24只,按体质量随机分为4组,正常对照组和3个实验组,实验组依据不同硫酸镍浓度又分为低剂量组(2.5 mg/kg)、中剂量组(5 mg/kg)和高剂量组(10 mg/kg),6只/组,等体积(5 mL/kg)腹腔注射硫酸镍染毒,1次/天,连续40日。正常对照组以生理盐水5 mL/kg等体积腹腔注射。染毒结束后检测大鼠促甲状腺激素(thyroid stimulating hormone,TSH)、生长激素(growth hormone,GH)、催乳素(prolactin,PRL)、卵泡刺激素(follicle stimulating hormone,FSH)、促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)、黄体生成素(luteinizing hormone,LH)和皮质醇水平的变化,观察垂体组织病理改变和凋亡蛋白Caspase-3表达情况。结果与对照组相比,低剂量组[(1.87±0.43)mU/L]和中剂量组[(2.28±0.93)mU/L]TSH水平明显降低(P<0.05),高剂量组[(2.85±0.77)mU/L]无明显降低(P>0.05),LH水平随着镍染毒剂量增加有升高趋势,仅高剂量组[(3.18±0.17)mIU/L]差异有统计学意义(P<0.05),GH、PRL、FSH、ACTH和皮质醇水平无明显改变(均P>0.05)。病理下中高剂量组垂体组织见少量淋巴细胞浸润。染镍组垂体Caspase-3表达均未见上调。结论硫酸镍能导致部分激素分泌异常,较高剂量引起垂体出现轻微病理改变,但是亚急性低剂量镍暴露不能引起凋亡指标明显改变。

Objective To investigate the functional and pathological damage of pituitary gland and the expression of Caspase-3 in rats after intraperitoneal injection of nickel sulfate.Methods Totally 24 healthy male Wister rats were randomly divided into four groups according to body weight,including normal control group and three experimental groups,and the experimental groups included the low dose group(2.5 mg/kg),medium dose group(5 mg/kg)and high dose group(10 mg/kg)according to the concentration of nickel sulfate,six rats in each group.The animals were exposed to equal volume(5 mL/kg)of nickel sulfate by intraperitoneal injection,once a day for 40 consecutive days.The normal control group was given intraperitoneal injection of 5 mL/kg normal saline.The changes of thyroid stimulating hormone(TSH),growth hormone(GH),prolactin(PRL),follicle stimulating hormone(FSH),adrenocorticotropic hormone(ACTH),luteinizing hormone(LH)and cortisol levels in rats were detected after the expsure.The pathological changes of pituitary tissue and the expression of Caspase-3 were observed.Results Compared with the control group,the TSH level in low dose group[(1.87±0.43)mU/L]and middle dose group[(2.28±0.93)m U/L]decreased significantly(P<0.05),while that in high dose group did not decrease significantly(P>0.05).LH level increased with the increase of nickel exposure dose,but only in high dose group[(3.18±0.17)mIU/L]had statistically significant difference(P<0.05),while the levels of GH,PRL,FSH,ACTH and cortisol did not change significantly(all P<0.05).Pathologically,a small amount of lymphocyte infiltration was found in pituitary tissue of middle and high dose group.The expression of Caspase-3 in pituitary was not up-regulated in nickel exposure group.Conclusion Nickel sulfate can cause abnormal secretion of some hormone,and higher dose can cause slight pathological changes in pituitary gland,but subacute low-dose nickel exposure can not cause obvious changes in apoptosis index.