黄芪桂枝五物汤对CIA模型大鼠关节滑膜细胞凋亡的影响  

Effect of Huangqi Guizhi Wuwutang on Joint Synovial Cell Apoptosis in CIA Rat Models

作　　者：刘佳维[1] 王永辉[1] 李艳彦[2] 张永刚[2] 赵乐[3] 张若楠[1] 

机构地区：[1]山西中医学院基础医学院,太原030024 [2]山西医科大学药学院,太原030001 [3]成都中医药大学,成都611137

出　　处：《中国实验方剂学杂志》2017年第14期171-176,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：山西省基础研究项目(2014011047-1)

摘　　要：目的:研究黄芪桂枝五物汤(HGW)对胶原诱导型关节炎(CIA)模型大鼠关节滑膜细胞凋亡的影响,并探讨其作用机制。方法:选用SD大鼠72只,随机分为正常组,模型组,HGW低、中、高剂量组,Tofacitinib(TFN)组,HGW低、中、高剂量组药物剂量分别为16,32,64 g·kg^(-1),相当于临床常人用量的3,6,12倍,TFN给药剂量为15 mg·kg^(-1),正常组、模型组每日给予10 m L·kg^(-1)蒸馏水。以牛Ⅱ型胶原加弗氏完全佐剂建立CIA大鼠模型,经HGW治疗4周后光镜下观察各组大鼠踝关节病理形态;通过流式细胞术检测白细胞介素(IL)-4,IL^(-1)0含量,免疫组化法检测B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2),Bcl-2相关X蛋白(Bax)蛋白表达,DNA断裂的原位末端标记法(TUNEL)染色检测滑膜细胞的凋亡。结果:与正常组比较,模型组,HGW低、中、高剂量组,TFN组大鼠滑膜中Bcl-2蛋白表达增多(P<0.05),模型组Bax蛋白表达减少(P<0.05);与模型组比较,HGW高剂量组,TFN组大鼠滑膜中Bcl-2蛋白表达减少,Bax蛋白表达增多(P<0.05)。滑膜细胞凋亡可见,与正常组比较,模型组,HGW低、中、高剂量组,TFN组滑膜细胞增多,凋亡率下降(P<0.05);与模型组比较,HGW低、中、高剂量组,TFN组大鼠滑膜细胞凋亡率上升(P<0.05);与HGW低剂量组比较,HGW高剂量组滑膜细胞凋亡率显著上升(P<0.01);与HGW-M组比较,HGW高剂量组滑膜细胞凋亡率上升(P<0.05)。结论:黄芪桂枝五物汤可以促进RA大鼠异常亢进的滑膜细胞凋亡。Objective： To investigate the effect of Huangqi Guizhi Wuwutang （HGW） on joint synovial cell apoptosis in rat models with collagen induced arthritis （CIA） , and explore its mechanism of action. Method： The 72 SD rats were randomly divided into 6 groups ： normal group （N） , model group （CIA） , HGW low, medium and high dose groups （HGW-L, M, H）, and Tofacitinih group （TFN）. The drug doses were 16, 32, 64 g.mL-1 respectively in HGW-L, HGW-M, HGW-H （16, 32, 64 g.kg-1） groups equivalent to 3, 6, 12 times of the dosage for clinical common people; the drug dose of TFN was 15 mg.kg-1; 10 mL.kg-1 distilled water was given daily in normal group and model group. Bovine type ]I collagen and Freund＇s complete adjuvant （FCA） were used to build collagen-induced arthritis rat models, and the ankle pathological morphology in rats was observed underlight microscope after 4 weeks treatment by HGW. Then the contents of IL-10 and IL-4 were detected by flow eytometry. The protein expression levels of Bcl-2 and Bax were detected by immunohistochemistry, and terminal dexynucleotidyl transferase （TdT） -mediated dUTP nick end labeling （TUNEL） staining was used to detect the apoptosis of synovial cells. Result： As compared with normal group, the protein expression levels of Bel-2 in synovium were increased in model group, HGW-L, M, H groups and TFN group （P 〈 0.05 ）; the protein expression levels of Bax were reduced in model group （P 〈 0.05）. As compared with model group, Bcl-2 protein expression levels were decreased in HGW-H group and TFN group, while Bax protein expressions were increased （P 〈 0.05 ）. Apoptosis of synovial cells was visible, and as compared with normal group, synovial cells were increased in model group, HGW-L, M, H groups and TFN group, with a decreased apoptosis rate （P 〈 0.05）. As compared with model group, the apoptosis rate of synovial cells was increased in HGW-L, M, in H groups and TFN group （P 〈 0.05）. As compared with HGW-L group, a

关 键 词：类风湿性关节炎 黄芪桂枝五物汤 滑膜细胞 凋亡 胶原诱导型关节炎 

分 类 号：R285.5[医药卫生—中药学]