| 摘要: |
| 目的研究急性百草枯中毒大鼠肾损伤炎症因子的动态变化及姜黄素的干预效果和机制。方法将60只SD大鼠随机分成正常对照组、姜黄素对照组、百草枯染毒组（2%百草枯溶液2ml/kg灌胃染毒）和姜黄素干预组（百草枯灌胃染毒后，每组各15只，分别在15min、24h和48h于腹腔内注射5ml/kg姜黄素。观察各组大鼠行为学改变。处理后第1、3、7天留取肾组织并抽取静脉血，采用苦味酸比色法测定血清肌酐水平，脲酶法测定尿素氮水平，ELISA法分别测定IL-1β、IL-6、IL-10和TNF-α水平，Westernblot检测大鼠肾组织NF-κB表达量。观察光镜下各组大鼠肾组织的病理变化。结果正常对照组、姜黄素对照组各大鼠活动灵敏，反应自如，进食正常，皮毛光滑。百草枯染毒组大鼠在染毒30min后活动增多，呈易惹状态，6h后表现懒散，活动量逐渐减少，走路晃动，呼吸急促，毛发战栗，不进食，3d时表现程度最重。姜黄素干预组以上症状均较百草枯染毒组为轻。与正常对照组比较，姜黄素对照组各项指标水平无明显变化（P＞0.05）。百草枯染毒组肌酐、尿素氮水平和NF-κB表达显著升高，肌酐、尿素氮水平在第3天达到峰值，NF-κB表达在第1、3、7天持续升高（均P＜0.05），百草枯染毒组IL-1β、IL-6、IL-10、TNF-α水平均显著升高，IL-1β、IL-10、TNF-α水平在第3天达峰值，IL-6水平则持续升高（均P＜0.05）。与百草枯染毒组相比，姜黄素干预组在第1、3、7天，肌酐、尿素氮水平和NF-κB表达显著下降，IL-1β、IL-6、TNF-α水平亦显著降低，IL-10水平则显著升高（均P＜0.05）。光学显微镜下可见，百草枯染毒组大鼠肾组织在染毒后第3天，病理损害最严重，各个时间点姜黄素干预组病理损害均较百草枯染毒组有所减轻。结论姜黄素可通过下调NF-κB的表达，降低肾组织中炎症因子TNF-α、IL-1β、IL-6水平，升高IL-10水平来减轻百草枯所致肾损伤的炎症反应，对急性百草枯中毒所致的肾损伤有一定的保护作用。 |
| 关键词: 姜黄素 百草枯 肾脏 炎症因子 大鼠 |
| DOI：10.12056/j.issn.1006-2785.2017.39.03.2016-1210 |
| 分类号: |
| 基金项目:浙江省医学创新学科建设计划（11-CX26）；浙江省“十二五”浙江省高校重点学科（2012-207） |
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| Effect of curcumin on inflammation in paraquat-induced renal injury in rats |
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CHEN Yanzhen, HAN Wenwen, LI Xiaolin, ZHAO Guangju, HONG Guangliang, LI Mengfang, LU Zhongqiu
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Yiwu Hospital of Wenzhou Medical University
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| Abstract: |
| Objective To investigate the effect of curcumin on inflammation in paraquat-induced kidney injury in rats. Methods Sixty male SD rats were divided into four groups randomly with 15 rats in each: the normal control group, curcumin control group, paraquat poisoning group(the rats were given 2ml/kg 2% paraquat solution by gavage), curcumin intervention group (the rats were intraperitoneally injected with 5ml/kg curcurmin at 15 min, 24 h, 48 h after gavage of paraquat). The behavior changes of rats were observed after treatment. On d1, 3 and 7, 5 rats in each group were sacrificed and the kidney tissues and serum samples were collected. The blood creatinine (Cr) and urea nitrogen (BUN) levels were measured by SOP-CR and urea assay, respectively, the interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor (TNF)-α levels were measured by ELISA. And the expression of nuclear factor(NF)-κB in nephrotic tissue was detected by Western blotting. Pathological changes of the kidney were observed with light microscopy. Results Compared to the rats in normal control and curcumin control group the rats in
paraquat poisoning group increased activity, irritability at 30min after injection, then appeared restless, less active, short of breath, stopped eating and walked staggeringly at 6h after injection, and on d3, the above symptoms were more severe. The symptoms of rats in curcumin intervention group were less severe than that in paraquat poisoning group. Compared to normal control group and
curcumin control group, the levels of Cr, BUN and the expression of NF-κB in paraquat poisoning group were increased, and the
Cr, BUN levels reached peak on d3, the expression of NF-κB continued to increase on d1, 3 and 7. The activity of IL-1β, IL-10 and TNF-α was significantly and reached peak on d3 (P＜0.05), the activity of IL-6 continued to increased significantly on d1, 3
and 7 . Compared with the paraquat poisoning group, the level of Cr, BUN and the expression of NF-κB in curcumin intervention group decreased significantly; IL-1β, IL-6, and TNF-α activity was significantly decreased too, and the level of IL-10, however, was significantly increased on d1, 3 and 7 (all P＜0.05). The pathological examination revealed that the damage of kidney tissue in the paraquat group was the most severe on d3 after paraquat exposure, and the damage was consistently alleviated in curcumin intervention group on d1, 3 and 7 as compared with the paraquat group. Conclusion Excessive inflammatory play an important role in paraquat-induced acute kidney damage. Our study shows that curcumin can exert a protective effect on paraquat-in- duced kidney damage in rats by down-regulate the expression of NF-κB, decreasing the activity of IL-1β, IL-6, TNF-α, de- creasing the levels of Cr, BUN, and increasing the activity of IL-10. |
| Key words: Curcumin Paraquat Kidney Inflammation Rat |
