Objective: To observe the effect of crotonaldehyde long-term exposure on kidney injury in male rats, and to explore the specific mechanism of toxic action. Methods: 32 specific pathogen free healthy adult male wistar rats were randomly divided into 4 groups with 8 rats in each group: high-, moderate-, low-dose groups and a control group. Rats were treated with 8.5, 4.5, 2.5 and 0.0 mg/kg body weight crotonaldehyde by gavage, once a day for consecutive 128 days. After the last treatment, they were sacrificed and separated bilateral kidney. Kidney organ coefficients were calculated and the histopathology changes in kidney were observed by HE staining. The activities of malondialdehyde (MDA) , superoxide dismutase (SOD) , glutathion peroxidase (GSH-Px) and the levels of malaondialdehyde uric acid (UA) , urea nitrogen (BUN) , creatinine (CR) in serum were determined in the same time. Moreover, the levels of interleukin (IL) -6, 8, interferon (IFN) -γ and tumor necrosis factor (TNF) -α in kidney were determined by enzyme linked immunosorbent assay. Results: Bilateral kidneys in the 8.5 mg/kg group were reduced in size and dark in color. Under the microscope, the major pathology changes of kidneys could be summarized as summarized as protein cast renal tubule, inflammatory cells and lymphocytes infiltration among kidney cortex. Compared with the control group, the weight gain of rats in 8.5 mg/kg group were smaller, and the weight and organ coefficient of kidney in each groups were significant decreased (P<0.05) . With the increasing dosage of crotonaldehyde, the serum BUN and UA levels in 8.5, 4.5 mg/kg groups, CR level in 8.5 mg/kg group were significant increased (P<0.05) .Compared with the control group, the serum MDA level in 8.5 mg/kg group was significant increased (P<0.05) . However, serum SOD activity in 8.5 mg/kg group and GSH-PX activity in 8.5, 4.5 mg/kg groups was significant decreased (P<0.05) . With the increasing dosage of crotonaldehyde, there are upward trend in the kidney IL-6, IL-8, TNF-α, IFN-γ, β-2 microglobulin levels. Compared with the control group, IL-6, TNF-α, IFN-γ, β-2microglobulin levels in 8.5, 4.5 mg/kg groups and IL-8 level in 8.5 mg/kg group in kidney were significant increased (P<0.05) . Conclusion: Crotonaldehyde could develop the inflammatory factors levels and change the oxidation balance condition in the kidney of male rats, causing the inflammatory and oxidative injures of renal tissues.
目的： 观察巴豆醛长期染毒致雄性大鼠肾脏炎性及氧化状态改变，探讨损伤的可能机制。 方法： SPF级雄性Wistar大鼠32只，随机分为8.5、4.5、2.5 mg/kg巴豆醛染毒组和对照组，每组8只，连续灌胃染毒128 d，每天1次，于末次染毒结束后处死并迅速分离双侧肾脏组织，精确测定其重量并进行组织病理学检查，测定血清超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）活力以及丙二醛（MDA）、尿酸（UA）、尿素氮（BUN）、肌酐（CR）含量，ELISA测定肾脏中的细胞介素（IL）-6、IL-8、肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ以及β(2)-微球蛋白表达水平。 结果： 8.5 mg/kg染毒组双侧肾脏组织体积缩小、颜色暗深，光学显微镜下观察可见肾皮质炎性细胞浸润以及蛋白管型肾小管为主的病理改变。与对照组比较，8.5 mg/kg染毒组大鼠体重增加量降低，各染毒组肾脏重量及脏器系数下降，差异有统计学意义（P<0.05）。与对照组比较，8.5、4.5 mg/kg染毒组血清BUN、UA以及8.5 mg/kg染毒组血清CR含量升高，差异有统计学意义（P<0.05）。与对照组比较，8.5 mg/kg染毒组血清MDA含量升高、SOD活力降低，8.5、4.5 mg/kg染毒组血清GSH-Px活力降低，差异均有统计学意义（P<0.05）。大鼠肾脏中IL-6、IL-8、TNF-α、IFN-γ、β(2)-微球蛋白水平呈上升趋势，与对照组比较，8.5、4.5 mg/kg染毒组IL-6、TNF-α、IFN-γ、β(2)-微球蛋白水平升高、8.5 mg/kg染毒组IL-8水平升高，差异有统计学意义（P<0.05）。 结论： 巴豆醛可能通过上调肾脏炎性因子表达，改变氧化平衡状态，促使大鼠肾脏发生炎性及氧化损伤。.
Keywords: Crotonaldehyde; Inflammatory Factors; Kidney; Kidney Function; Oxidative Stress.