Ouyang Chuan, Ke Hongyang, Zhou Jian, Zhao Jiali, Ma Xuan, Liu Yumei, Li Xiaohong, Li Wanwei
School of Public Health, Weifang Medical College, Weifang 261053, China.
School of Public Health, Weifang Medical College, Weifang 261053, China Key Laboratory of Health Inspection and Quarantine, Weifang 261053, China.
Wei Sheng Yan Jiu. 2022 Sep;51(5):791-807. doi: 10.19813/j.cnki.weishengyanjiu.2022.05.019.
To investigate the renal injury induced by cadmium chloride(CdCl_2) and the protective effect of vitamin C(VC) in mice.
Forty healthy clean grade male Kunming mice were randomly divided into 4 groups: control group(double distilled water gavage and intraperitoneal injection), VC group(200 mg/kg VC gavage and double distilled water intraperitoneal injection), CdCl_2 group(double distilled water gavage and 2 mg/kg CdCl_2 intraperitoneal injection), VC+CdCl_(2 )group(200 mg/kg VC gavage and 2 mg/kg CdCl_2 intraperitoneal injection). Exposure for 30 days.24 hours after the last exposure, the eyeballs were taken out for blood, and the renal tissue was immediately taken out to calculate kidney coefficient and then separate renal cells. The levels of reactive oxygen species(ROS) were detected by DCFH-DA kit and flow cytometry. Blood urea nitrogen(BUN), serum creatinine(Scr)and β2 microglobulin(β2-MG), cystatin C(Cys C), superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), malondialdehyde(MDA), Caspase3 and Caspase9 kits were used to detect the corresponding indicators respectively. The contents of Cd(2+) and Zn(2+) in serum and kidney were detected by graphite furnace atomic absorption spectrometry.
The levels of kidney coefficient and BUN, Scr, β2-MG were 1.36±0.10, (19.34±0.63)mmol/L, (61.30±2.04)mmol/L and(1.02±0.10)g/mL respectively in CdCl_(2 )group, which were higher than those in the control group and VC group(P<0.05). The levels of the above four indexes in VC+CdCl_(2 )group were 1.09±0.10, (9.65±0.50)mmol/L, (41.85±1.27)mmol/L and(0.61±0.01)g/mL respectively, which were lower than those in CdCl_2 group(P<0.05). CdCl_2 exposure resulted in unclear glomerular contour, swelling of renal tubules, interstitial hyperemia, and exfoliated epithelial cells in the lumen. VC pretreatment could improve the above changes. The levels of Cd(2+) in serum and renal tissue of mice in CdCl_2 group were(4.36±0.07)μg/L, (18.6±1.95)μg/g respectively, which were higher than that of control group and VC group(P<0.05), in VC+CdCl_2 group, the level were(2.12±0.06)μg/L and(2.18±0.09)μg/g, they were lower than that of CdCl_2 group(P<0.05). The level of serum Zn(2+ )in CdCl_2 group was(11.35±1.03)μg/L, that was lower than control group(P<0.05). The level of serum Zn~(2+) in VC+CdCl_2 group was(26.98±3.13)μg/L, which was higher than that of CdCl_2 group(P<0.05). The levels of ROS, MDA, Caspase3 and Caspase9 in kidney tissue of mice in CdCl_2 group were(1.86±0.13), (4.78±0.15)nmol/mg, 1.50±0.24 and 1.69±0.17 respectively, which were higher than those in control group(P<0.05). And the level of GSH-Px was(261.3±23.36)U/mg, it was lower than that in control group(P<0.05). Compared with the CdCl_2 group, the levels of ROS, MDA, Caspase3 and Caspase9 in VC+CdCl_2 group decreased, and the level of GSH-Px increased, the difference was statistically significant(P<0.05).
CdCl_2 exposure can lead to oxidative stress, damage of glomerulus and renal tubules, imbalance of zinc ion homeostasis, and damage of renal function. VC pretreatment can reduce the damage caused by CdCl_2 to a certain extent.
探讨氯化镉(CdCl₂)诱导的小鼠肾损伤及维生素C(VC)的保护作用。
将40只健康清洁级雄性昆明小鼠随机分为4组:对照组(双蒸水灌胃及腹腔注射)、VC组(200 mg/kg VC灌胃及双蒸水腹腔注射)、CdCl₂组(双蒸水灌胃及2 mg/kg CdCl₂腹腔注射)、VC+CdCl₂组(200 mg/kg VC灌胃及2 mg/kg CdCl₂腹腔注射)。染毒30天。末次染毒后24小时,摘眼球取血,立即取出肾组织计算肾系数,然后分离肾细胞。采用DCFH-DA试剂盒和流式细胞术检测活性氧(ROS)水平。分别用尿素氮(BUN)、血清肌酐(Scr)、β2微球蛋白(β2-MG)、胱抑素C(Cys C)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、Caspase3和Caspase9试剂盒检测相应指标。采用石墨炉原子吸收光谱法检测血清和肾脏中Cd²⁺和Zn²⁺的含量。
CdCl₂组肾系数及BUN、Scr、β2-MG水平分别为1.36±0.10、(19.34±0.63)mmol/L、(61.30±2.04)mmol/L和(1.02±0.10)g/mL,高于对照组和VC组(P<0.05)。VC+CdCl₂组上述4项指标水平分别为1.09±0.10、(9.65±0.50)mmol/L、(41.85±1.27)mmol/L和(0.61±0.01)g/mL,低于CdCl₂组(P<0.05)。CdCl₂染毒导致肾小球轮廓不清、肾小管肿胀、间质充血,管腔内有脱落的上皮细胞。VC预处理可改善上述改变。CdCl₂组小鼠血清和肾组织中Cd²⁺水平分别为(4.36±0.07)μg/L、(18.6±1.95)μg/g,高于对照组和VC组(P<0.05);VC+CdCl₂组分别为(2.12±0.06)μg/L和(2.18±0.09)μg/g,低于CdCl₂组(P<0.05)。CdCl₂组血清Zn²⁺水平为(11.35±1.03)μg/L,低于对照组(P<0.05)。VC+CdCl₂组血清Zn²⁺水平为(26.98±3.13)μg/L高于CdCl₂组(P<0.05)。CdCl₂组小鼠肾组织中ROS、MDA、Caspase3和Caspase9水平分别为(1.86±0.13)%、(4.78±0.15)nmol/mg、1.50±0.24和1.69±0.17,高于对照组(P<0.05);GSH-Px水平为(261.3±23.36)U/mg,低于对照组(P<0.05)。与CdCl₂组比较,VC+CdCl₂组肾组织中ROS、MDA、Caspase3和Caspase9水平降低,GSH-Px水平升高,差异有统计学意义(P<0.05)。
CdCl₂染毒可导致氧化应激、肾小球和肾小管损伤、锌离子稳态失衡及肾功能损害。VC预处理可在一定程度上减轻CdCl₂所致损伤。