硫酸铟对大鼠肾脏的损害作用

Renal damage of indium sulfate on rats

目的探讨硫酸铟亚慢性经口染毒对大鼠的肾脏损害作用。方法选取4周龄SPF级雄性Wistar大鼠32只,随机分成对照组(生理盐水)、硫酸铟低剂量组(52.3 mg/kg)、中剂量组(104.6 mg/kg)和高剂量组(261.4 mg/kg),每组8只。采用灌胃方式进行染毒,1次/天,5天/周,连续染毒8周,染毒结束后收集24 h尿液;次日处死前称重,并收集血液和肾脏。采用试剂盒测定血清肌酐(Cr)、尿素氮(BUN)、白蛋白(ALB)、总抗氧化能力(T-AOC),以及肾组织微量还原型谷胱甘肽(GSH)含量;采用酶联免疫吸附法(ELISA)测定血清和尿液中β2-微球蛋白(β2-MG)含量;采用电感耦合等离子体质谱(ICP-MS)法测定血液、尿液和肾组织中的铟含量;采用HE染色对肾组织进行病理形态学观察。结果实验期间,各组大鼠一般状况正常,体重稳定增长,在染毒第7周和第8周时,高剂量染毒组大鼠体重明显低于对照组(P<0.05)。与对照组比较[(1.27±0.55)、(0.40±0.01)和(0.30±0.06)μg/L],3个剂量组大鼠血铟[(44.10±23.10)、(52.08±21.03)和(67.42±45.98)μg/L]、尿铟[(0.72±0.13)、(2.75±0.15)和(4.31±0.33)μg/L]和肾铟含量[(1.36±0.83)、(1.52±0.49)和(2.87±0.20)μg/g]均显著升高(P<0.05);高剂量染毒组大鼠血清中Cr明显高于对照组[(66.06±18.62)μmol/L和(46.53±7.95)μmol/L,P<0.05],高剂量组和中剂量组大鼠血清BUN含量[(3.98±0.82)mmol/L和(4.09±0.71)mmol/L]明显低于对照组[(4.77±0.49)mmol/L,P<0.05];3个剂量组血清和尿液中β2-MG水平较对照组均明显升高(P<0.05);3个剂量组大鼠血清T-AOC水平[(4.87±2.36)、(4.50±2.33)和(4.00±3.29)U/m L]和肾组织GSH水平[(6.41±1.86)、(5.06±2.09)和(2.77±2.64)μmol/(g prot)]均明显低于对照组[(15.20±5.43)U/mL和(14.74±6.47)μmol/(g prot),P<0.05];中、高剂量染毒组与对照组比较有明显的炎症性病理改变,主要表现为肾小球肿胀、肾小管结构异常和炎性细胞浸润等。结论硫酸铟灌胃染毒会引起大鼠肾脏铟的蓄积、发生氧化损伤、病理改变以及功能障碍等。

Objective To study the renal damage of indium sulfate. Methods 32 healthy Wistar rats were randomly and equally divided into 3 dose groups（ 52. 3 mg/kg、104. 6 mg/kg 和 261. 4 mg/kg） and one negative control group. Indium sulfate were orally given once a day successively 5 days a week for 8 weeks. Each group of rats was collected24 hour urine after the end of the posion. We tested the content of Cr,BUN,T-AOC,ALB in serum and the GSH activity in kidney by kids and detected the β2-MG content in serum and urine by ELISA test. Inductively coupled plasma mass spectrometry（ ICP-MS）method was used to detect the content of indium in whole blood,urine and kidney tissue of rats. Hematoxylin and eosin（ HE） staining was used to detect histological changes.Results During the experiment,all the rats were normal in activities,feed and drinking water,and they developed stably. In the period of seventh weeks and eighth weeks,the body weight of rats in high dose group was significantly lower than the control group（ P〈0. 05）. Compared with the control group[（ 1. 27 ± 0. 55）,（ 0. 40 ± 0. 01） and（ 0. 30 ±0. 06） μg/L],3 dose group of indium in blood[（ 44. 10 ± 23. 10）,（ 52. 08 ± 21. 03） and（ 67. 42 ± 45. 98） μg/L],urine[（ 0. 72 ± 0. 13）,（ 2. 75 ± 0. 15） and（ 4. 31 ± 0. 33）μg/L]and kidney [（ 1. 36 ± 0. 83）,（ 1. 52 ± 0. 49） and（ 2. 87 ± 0. 20） μg/L] were significantly increased（ P〈0. 05）. The level of Cr in serum in the high dose group were significantly higher than that in the control group [（ 66. 06 ± 18. 62） and（ 46. 53 ± 7. 95）μmol/L,P〈0. 05],the serum BUN content[（ 3. 98 ± 0. 82） and（ 4. 09 ± 0. 71） mmol/L] in the high dose group and middle dose group were significantly lower than the control group [（ 4. 77 ± 0. 49） mmol/L,P〈0. 05]. Compared with the control group,3 dose group of the β2-MG in serum and urine were significantly increased（ P〈0. 05）,and the level of T-AOC[（ 4. 87 ± 2. 36）,（ 4. 50 ± 2. 33） and（ 4. 00 ± 3. 29） U/m L] in serum and GSH[（ 6. 41 ± 1. 86）,（ 5. 06 ± 2. 09） and（ 2. 77 ± 2. 64） μmol/（ g prot） ] in renal tissue were significantly decreased[（ 15. 20 ± 5. 43） U/m L and（ 14. 74 ± 6. 47） μmol/（ g prot）,P〈0. 05]. Compared with the control group,the middle and high dose exposure group had significant inflammatory pathological changes,mainly manifested as glomerular swelling, renal tubular structure abnormalities and inflammatory cell infiltration.Conclusion Indium sulfate can cause the accumulation of indium in the kidney,oxidative damage,pathological changes and dysfunction in the kidney of rats.