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目的按照对比剂肾病(contrast-induced nephropathy,CIN)的造模方法,建立对比剂急性肾损伤大鼠模型,使用姜黄素(curcumin,CUR)进行干预研究,探究姜黄素对低渗性非离子型对比剂碘海醇造成的大鼠急性肾损伤的保护作用及可能机制,以期为对比剂肾病的预防和治疗提供更多证据。方法将30只清洁级雄性SD大鼠随机分为对照组(control group,CON组)、对比剂肾病组(contrast-media nephropathy group,CM组)及姜黄素干预组(curcumin group,CUR组),每组各10只。CUR组大鼠连续给予姜黄素灌胃5天,其余两组大鼠给予相应体积溶剂灌胃。于造模48h后,检测血清肌酐(SCr)、尿素氮(BUN)水平测定肾功能;HE染色观察肾脏病理变化并评估肾小管损伤程度;应用氧化应激指标检测试剂盒检测肾脏组织内总超氧化物歧化酶(T-SOD)活性及丙二醛(MDA)含量;免疫印迹(Western blot,WB)法检测各组大鼠Sirt1、NF-κB的表达水平。结果与CON组相比,CM组血Scr、BUN水平显著升高,肾组织匀浆SOD活力、Sirt1表达水平均明显降低,肾组织MDA含量、NF-κB表达水平均明显增高,差异均有统计学意义(P<0.01),且HE染色可见CM组大鼠肾脏肾小管损伤严重,髓质充血,肾小管结构破坏明显,上皮细胞刷状缘脱落、空泡变性、细胞坏死及蛋白质管型沉积等病理改变,肾小管损伤评分显著升高,差异有统计学意义(P<0.05);与CM组相比,CUR组Scr、BUN水平显著降低,肾组织匀浆SOD活力、Sirt1表达水平均明显升高,肾组织MDA含量、NF-κB表达水平均明显降低,差异均有统计学意义(P<0.05),病理可见点状肾小管上皮细胞空泡变性,且表现为胞质内细小空泡,少量蛋白管型及髓质充血,肾小管损伤评分较CM组减低,且差异有统计学意义(P<0.05)。结论姜黄素能显著减轻对比剂对肾小管上皮细胞的损伤,姜黄素对CIN的保护作用可能是通过抗氧化应激、抗炎途径来完成的,姜黄素可能通过上调Sirt1的表达来改善对比剂所致的急性肾损伤。
OBJECTIVE: To establish a rat model of contrast-induced nephropathy (CIN) and establish a rat model of acute renal injury with contrast agent. Curcumin (CUR) was used to study the effects of curcumin on hypotonic nonionic Contrast agent iohexol induced acute renal injury in rats and its possible mechanism in order to provide more evidence for the prevention and treatment of contrast nephropathy. Methods Thirty clean-grade male SD rats were randomly divided into control group (CON), contrast-media nephropathy group (CM) and curcumin group (CUR) Each group of 10. CUR group rats were given continuous feeding of curcumin 5 days, the other two groups were given the corresponding volume of solvent gavage. At 48h after modeling, serum creatinine (SCr) and blood urea nitrogen (BUN) levels were measured to determine the renal function. The renal pathological changes were observed by HE staining and the degree of renal tubular injury was evaluated. The oxidative stress indicator kit (T-SOD) activity and malondialdehyde (MDA) content. The expression of Sirt1 and NF-κB in each group were detected by Western blot (WB). Results Compared with the CON group, the levels of Scr and BUN in the CM group were significantly increased, while the SOD activity and the Sirt1 expression in the renal tissue homogenate were significantly decreased. The content of MDA and the expression of NF-κB in renal tissue were significantly increased (P <0.01). The damage of renal tubules in rats of CM group was serious, the hyperemia of medulla, the destruction of tubular structure, the detached brush border, the degeneration of vacuoles, the necrosis of cells and the protein tube deposition (P <0.05) .Compared with CM group, the levels of Scr and BUN in CUR group were significantly decreased, while the SOD activity and Sirt1 expression in renal tissue homogenate were significantly higher than those in CM group (P <0.05). The pathological changes of vacuolar degeneration of punctate renal tubular epithelial cells were observed, and the expression of cytoplasmic small vacuoles , A small amount of protein tube and medulla congestion, renal tubular injury score decreased compared with CM group, and the difference was statistically significant (P <0.05). Conclusion Curcumin can significantly reduce the damage of contrast agent to renal tubular epithelial cells. The protective effect of curcumin on CIN may be through anti-oxidative stress and anti-inflammatory pathway. Curcumin may improve the contrast agent by up-regulating the expression of Sirt1 Caused by acute kidney injury.