Li Bodong, Xie Haibo, Wang Xian, Yang Xiaodong, Yang Ling, Zhang Jiaxiang, Wang Feng, Shen Tong, Zhu Qixing
Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, China.
Institute of Dermatology, First Affiliated Hospital of Anhui Medical University, China.
J Toxicol Sci. 2019;44(5):317-326. doi: 10.2131/jts.44.317.
The purpose of this study was to explore whether renal endothelial cell injury is associated with oxidative stress in trichloroethylene (TCE)-induced immune kidney damage by detecting adhesion molecules and oxidative stress indexes. In this study, a mouse model of skin sensitization with the antioxidant Tempol was used to explore the mechanism. Blood urea nitrogen (BUN), creatinine (Cre), and histological examination were used for kidney function evaluation. Kidney homogenates were used for detecting renal nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD) and malondialdehyde (MDA). Renal endothelial nitric oxide synthase (eNOS), E-selectin, vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecule (ICAM-1) protein levels were measured by immunohistochemical and Western blot. We found that BUN and Cre levels increased in the TCE sensitization positive group and the TCE+Tempol sensitization positive group. In the TCE sensitization positive group, a partial area of vacuolar degeneration and lysed epithelial cells were observed in renal tubules. In TCE+Tempol sensitization positive group, small areas were also found to be vacuolar degenerated and renal tubules were dissolved. Renal NO, NOS, SOD and eNOS levels decreased and MDA levels increased, renal E-selectin, VCAM-1and ICAM-1 protein levels increased in the TCE sensitization positive group and the TCE+Tempol sensitization positive group. Tempol attenuated TCE induced up-regulation of MDA, E-selectin, VCAM-1and ICAM-1 and down-regulation of NO, NOS, SOD and eNOS. In conclusion, trichloroethylene-sensitized mice renal immune injury is associated with the renal endothelial cells' oxidative stress state.
本研究旨在通过检测黏附分子和氧化应激指标，探讨三氯乙烯（TCE）诱导的免疫性肾损伤中肾内皮细胞损伤是否与氧化应激相关。本研究采用抗氧化剂Tempol建立皮肤致敏小鼠模型以探究其机制。采用血尿素氮（BUN）、肌酐（Cre）及组织学检查评估肾功能。取肾匀浆检测肾一氧化氮（NO）、一氧化氮合酶（NOS）、超氧化物歧化酶（SOD）和丙二醛（MDA）。采用免疫组化和蛋白质印迹法检测肾内皮型一氧化氮合酶（eNOS）、E选择素、血管细胞黏附分子（VCAM-1）和细胞间黏附分子（ICAM-1）蛋白水平。我们发现，TCE致敏阳性组和TCE+Tempol致敏阳性组的BUN和Cre水平升高。TCE致敏阳性组肾小管可见部分区域空泡变性和上皮细胞溶解。TCE+Tempol致敏阳性组也发现小面积空泡变性和肾小管溶解。TCE致敏阳性组和TCE+Tempol致敏阳性组肾NO、NOS、SOD和eNOS水平降低，MDA水平升高，肾E选择素、VCAM-1和ICAM-1蛋白水平升高。Tempol可减轻TCE诱导的MDA、E选择素、VCAM-1和ICAM-1上调以及NO、NOS、SOD和eNOS下调。综上所述，三氯乙烯致敏小鼠的肾免疫损伤与肾内皮细胞的氧化应激状态有关。
