防风石油醚提取物对胶原诱导型关节炎大鼠P38 MAPK磷酸化和AQP-1表达的影响  

Effects of Petroleum Ether Extract of Saposhnikovia divaricata on p38MAPK Phosphorylation and AQP-1 Expression in Collagen-Induced Arthritis Rats

作　　者：宋献美 李兵杰 张艳燕 葛文静 王慧森[2] 李更生[2] 梁瑞峰[2,3] Song Xianmei;Li Bingjie;Zhang Yanyan;Ge Wenjing;Wang Huisen;Li Gengsheng;Liang Ruifeng(Henan Medical College,Zhengzhou 451191;Henan Academy of Chinese Medicine,Zhengzhou 450004;Henan University of Chinese Medicine,Zhengzhou 450046)

机构地区：[1]河南医学高等专科学校,郑州451191 [2]河南省中医药研究院,郑州450004 [3]河南中医药大学,郑州450046

出　　处：《中药药理与临床》2021年第5期80-85,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(编号:81873022);河南省中医药科研重大专项(编号:2019ZYZD09);河南省中医药科研专项普通课题(编号:2016ZY2022)。

摘　　要：目的:探讨P38丝裂原活化蛋白激酶(P38 MAPK)信号通路在防风石油醚提取物调控胶原诱导型关节炎(CIA)大鼠滑膜组织水通道蛋白-1(AQP-1)表达中的作用。方法:将60只雄性SD大鼠随机分为正常对照组、模型对照组、P38МAРK抑制剂SB20358010 mg/kg组、防风石油醚提取物55、110、220 mg/kg组,除正常对照组外,其余大鼠注射Ⅱ型胶原建立胶原型关节炎模型,于造模当天开始给药,连续28 d,检测大鼠足趾肿胀度,观察踝关节组织病理学变化,ELISA法检测血清中白介素-1β(IL-1β)、IL-6、肿瘤坏死因子-α(TNF-α)和前列腺素E_(2)(PGE_(2))的含量,免疫组化法检测踝关节基质金属蛋白酶-13(MMP-13)的表达,蛋白免疫印迹法(Western blot)检测滑膜组织中P38 MAPK、磷酸化P38 MAPK(p-P38 MAPK)和AQP-1的蛋白表达。结果:与正常对照组比较,模型对照组大鼠足趾肿胀度明显增加,血清中IL-1β、IL-6、TNF-α和PGE_(2)含量升高,踝关节MMP-13蛋白表达上调,滑膜组织p-P38 MAPK和AQP-1的蛋白表达及p-P38 MAPK/P38 MAPK比值显著升高(P<0.01)。与模型对照组相比,防风石油醚提取物110、220 mg/kg组和SB20358010 mg/kg组大鼠的足趾肿胀度减轻,血清中IL-1β、IL-6、TNF-α和PGE_(2)含量降低,滑膜增生明显改善,MMP-13蛋白表达下调,滑膜组织中p-P38 MAPK和AQP-1的蛋白表达及p-P38 MAPK/P38 MAPK比值降低(P<0.05或P<0.01)。结论:防风石油醚提取物可有效减轻CIA大鼠关节肿胀和炎症反应,其作用机制可能与抑制P38 MAPK信号通路,下调AQP-1蛋白表达有关。Objective:To investigate the effects of the petroleum ether extract of Saposhnikovia divaricata on the expression of aquaporin-1(AQP-1)in collagen-induced arthritis(CIA)rats via p38 mitogen-activated protein kinase(p38 MAPK)signaling pathway.Methods:Sixty male SD rats were randomly divided into a normal group,a model group,a p38 MAPK inhibitor SB203580(10 mg/kg)group,and low-(55 mg/kg),medium-(110 mg/kg),and high-dose(220 mg/kg)petroleum ether extract of S.divaricate groups.The CIA model was induced by injection of typeⅡcollagen in rats except those in the normal group.The rats started to receive drug treatment on the modeling day,and drug treatment lasted for 28 days.The changes in paw swelling were detected and histopathological changes of ankle joint were observed.The content of interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),and prostaglandin E_(2)(PGE_(2))in the serum was detected by enzyme-linked immunosorbent assay(ELISA).The expression of matrix metalloproteinase-13(MMP-13)in the ankle joint was detected by immunohistochemistry.Protein expression levels of p38 MAPK,phosphorylated-P38 MAPK(p-p38 MAPK),and AQP-1 in synovial tissues were detected by Western blot.Results:Compared with the normal group,the model group showed severe paw swelling,elevated serum levels of IL-1β,IL-6,TNF-α,and PGE_(2),up-regulated expression of MMP-13 in the ankle joint,and increased expression of p-p38 MAPK,AQP-1,and p-p38 MAPK/p38 MAPK ratio in synovial tissues(P<0.01).Compared with the model group,the SB203580 group,and the medium and high-dose petroleum ether extract of S.divaricate groups displayed relieved paw swelling,decreased serum levels of IL-1β,IL-6,TNF-α,and PGE_(2),improved hyperplasia of synovium,down-regulated expression of MMP-13,and declining expression of p-p38 MAPK,AQP-1,and p-p38 MAPK/p38 MAPK ratio in synovial tissues(P<0.05 or P<0.01).Conclusion:The petroleum ether extract of S.divaricata can effectively reduce joint swelling and inflammation in CIA rats.Its mechanism may be related to th

关 键 词：防风 胶原诱导性关节炎 炎症反应 P38丝裂原活化蛋白激酶 水通道蛋白-1 

分 类 号：R285.5[医药卫生—中药学]