白藜芦醇介导SHh信号通路在佐剂性关节炎大鼠肾脏损伤中的作用研究  

Reseratrol attenuates renal injury by inhibiting the activation of SHh signaling pathway in adjuvant arthritis rats

作　　者：谢琳琳[1] 宋先兵[1] 汪晓庆[1] 杨珺[1] 程鹏[2] XIE Linlin;SONG Xianbin;WANG Xiaoqing;YANG Jun;CHENG Peng(Department of Pathology,Anhui Medical College,Hefei,Anhui 230601,China;Department of Thoracic Surgery,the First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei,Anhui 230032)

机构地区：[1]安徽医学高等专科学校病理学教研室,安徽合肥230601 [2]安徽中医药大学第一附属医院胸外科,安徽合肥230032

出　　处：《徐州医科大学学报》2018年第7期427-432,共6页Journal of Xuzhou Medical University

基　　金：安徽高校自然科学重点研究项目（KJ2015A359;KJ2017A699）

摘　　要：目的探讨白藜芦醇（resveratol，RES）对佐剂性关节炎（AA）大鼠关节炎症及肾脏损伤的治疗效果及其分子机制。方法将56只SD大鼠随机分为空白组（n=8）、溶剂组（n=8）、AA模型组（n=10）、AA＋RES低剂量组[n=10，5mg／（kg·d）]，AA＋RES中剂量组[n=10，10mg／（kg·d）]，AA＋RES高剂量组[n=10，15mg／（kg·d）]。采用弗氏完全佐剂建立AA大鼠模型，通过足爪肿胀度测量、动物全身炎症反应和关节炎症评分的方法进行模型建立评价。各组大鼠肾脏生化功能改变采用生化法检测，Westemblot法检测各组大鼠肾脏SHh蛋白表达水平，实时定量PCR法染色检测各组大鼠肾脏Glil、Smo和PtchlmRNA表达情况。结果RES高剂量组的足爪肿胀度和关节评分明显低于模型组和溶剂组，生化检测发现RES能改善肾脏肌酐（cr）和尿素氮（BUN）的表达水平，Westernblot检测结果高剂量RES能够降低AA大鼠。肾脏组织SHh蛋白表达水平，实时定量PCR检测发现RES能够降低大鼠肾脏组织Glil、SmomRNA表达，升高PtchlmRNA表达。结论RES能够明显改善AA大鼠的关节炎症和肾脏损伤程度，其机制可能为下调SHh信号通路活性。Objective To investigate the therapeutic effects of resveratrol on adjuvant arthritis rats and related molecular mechanisms. Methods A total of 56 SD rats were randomly divided into a control group （n = 8） , a solvent group （ n =8） , an adjuvant arthritis （AA） model group （n = 10） , an AA ＋ low - dose RES group[ n = 10, 5 mg/（kg · d） ] , an AA ＋ moderate - dose RES group [ n = 10, 10 mg/（ kg · d） ], and an AA ＋ high - dose RES group [ n = 10, 15 mg/（ kg · d） ]. An AA rat model was established using Freund＇s complete adjuvant, and evaluated by measurement of paw swelling, systemic inflammation and arthritis scoring. The changes of rat renal function were detected by biochemical methods. The level of SHh was examined by Western blot. The amounts of Glil, Smo and Ptchl mRNA in rat kidney of each group were detected by real - time ELISA. Results The AA ＋ high - dose RES group demonstrated significant lower paw swelling and joint scores than the model and solvent groups. RES could improve the BUN and Cr expression. High - dose RES reduced SHh levels in AA rat kidney tissues by Western blot. Real - time PCR detection showed that RES could reduce the levels of Glil, Smo mRNA but increased Ptchl mRNA amounts in rat kidneys. Conclusions RES could alleviate arthritis and kidney damage in AA rats, which may be related with down - regulated SHh signaling pathway.

关 键 词：佐剂性关节炎 白藜芦醇 SHH信号通路 肾脏损伤 

分 类 号：R332.72[医药卫生—人体生理学]