姜黄素上调Sirt1表达预防对比剂急性肾损伤的实验研究
投稿时间:2016-04-16  修订日期:2016-05-04  点此下载全文
引用本文:张德兵,李文华,刘娜娜,王虎,郑迪.姜黄素上调Sirt1表达预防对比剂急性肾损伤的实验研究[J].医学研究杂志,2016,45(12):133-137,156
DOI: 10.11969/j.issn.1673-548X.2016.12.036
摘要点击次数: 1048
全文下载次数: 754
作者单位E-mail
张德兵 221001 徐州医学院心血管病研究所  
李文华 221001 徐州医学院附属医院心内科 xzwenhua0202@163.com 
刘娜娜 221001 徐州医学院心血管病研究所  
王虎 221001 徐州医学院心血管病研究所  
郑迪 221001 徐州医学院附属医院心内科  
中文摘要: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。
中文关键词:姜黄素  对比剂急性肾损伤  氧化应激  Sirt1
 
Effect of Curcumin Intervention on Contrast-induced Kidney Injury in Experimental Rats through Upregulating the Expression of Sirt1
Abstract:Objective To observe the effect of curcumin (CUR) intervention on contrast-induced acute kidney injury in experimental rats, and to explore the beneficial effects and the possible mechanism of curcumin intervention on acute kidney injury in experimental rats by the low non-ionic contrast medium, in order to provide more theoretical basis for treating such injury in clinical practice.Methods A total of 30 male SD rats were randomly divided into 3 groups:control group, contrast-induced nephropathy group and curcumin group, ten of each group.The rats of curcumin group received intra-gastric curcumin for 5 days, the other two groups were given the corresponding volume of solvent for 5 days. After 48 hours of building model, the renal function was evaluated by serum creatinine(Scr) and urea nitrogen(BUN), the pathological change of the renal tissue was observed by HE staining to evaluate the degree of renal tissue injury, the nephridial oxidative stress indexes of malonadehyde (MDA) level and super oxide dismutase (SOD) activity were measured by the operating kits, then the protein expression of Sirt1 and NF-κB was examined by westernblot.Results Compared with control group, contrast-induced nephropathy group had significantly increased levels of Scr,BUN,MDA, NF-κB and decreased SOD activity, Sirt1 level (respectively P<0.01). The HE staining of the rats in contrast-induced nephropathy group showed severe tubular injure, medullary congestion, obvious tubular structure damage, epithelial cell brush border loss, vacuolar degeneration, necrosis and protein deposition, and had increased scores of tubular injure (P<0.05). Compared with contrast-induced nephropathy group, curcumin group had obviously decreased levels of Scr,BUN, MDA, NF-κB, and increased SOD activity, Sirt1 level(respectively P<0.05).The HE staining of the rats in curcumin group showed lower pathological injure as the contrast-induced nephropathy group, which had decreased scores of tubular injure (P<0.05).Conclusion Curcumin can obviously alleviate the injure of tubular epithelial cell form iohexol.Protective effects of curcumin to the rats may be through the way of inhibitting oxidative stress and anti-apoptotic to complete. Curcumin could probably protect against acute kidney injury through upregulating expression of Sirt1 in experimental rats.
keywords:Curcumin  Contrast-induced nephropathy  Oxidative stress  Sirt1
查看全文  查看/发表评论  下载PDF阅读器

京公网安备 11010502037822号