来源：风湿病与关节炎,2020,9（7）:1-6,19.

雷公藤多苷对胶原诱导性关节炎大鼠下丘脑视交叉上核Bmal1、Clock表达的调节作用（基础研究）

王少贤^1,2，李振彬¹

　　【摘　要】目的：观察胶原诱导性关节炎（CIA）大鼠下丘脑视交叉上核（SCN）生物钟基因Bmal1、Clock的表达变化，以及雷公藤多苷的调节作用。方法：建立CIA大鼠模型，随机分为模型对照组、醋酸泼尼松组、雷公藤多苷组，并设空白对照组，每组8只。醋酸泼尼松组、雷公藤多苷组分别于20：00灌胃给药，雷公藤多苷用药量10.5 mg·kg^-1·d^-1，醋酸泼尼松片用药量1.5 mg·kg^-1·d^-1；空白对照组、模型对照组灌服生理盐水。连续给药6周。观测各组大鼠足爪、关节肿胀情况，ELISA法测定血清肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6水平，qRT-PCR和Western-blot法检测SCN Bmal1、Clock基因和蛋白表达。结果：①实验结束，与空白对照组比较，CIA模型大鼠左后踝关节围长、足跖厚度、足趾容积、关节炎指数（AI）评分均明显增加（P < 0.05），血清TNF-α、IL-1β、IL-6水平明显升高（P < 0.05），下丘脑SCN Bmal1、Clock蛋白和基因表达均明显下降（P < 0.05）。②与模型对照组比较，醋酸泼尼松组、雷公藤多苷组均能明显改善大鼠足爪、关节肿胀程度，降低血清TNF-α、IL-1β、IL-6水平，增加SCN Bmal1、Clock蛋白和基因表达（P < 0.05），雷公藤多苷组对SCN Bmal1表达的调节作用优于醋酸泼尼松组（P < 0.05）。结论：关节炎的发病影响了血清炎性细胞因子和下丘脑SCN生物钟的表达；雷公藤多苷治疗CIA模型大鼠关节炎症的作用机制与调控下丘脑SCN核心钟基因表达和外周炎性细胞因子分泌水平相关。

　　【关键词】　胶原诱导性关节炎；雷公藤多苷；下丘脑视交叉上核；生物钟；Bmal1；Clock；大鼠

Regulation of Tripterygium Glycosides for the Expression of Bmal1 and Clock in Suprachiasmatic Nucleus of Hypothalamus in Collagen Induced Arthritis Rats

WANG Shao-xian,LI Zhen-bin

　　【ABSTRACT】Objective:To observe the expression of CLOCK and Bmall in suprachiasmatic nucleus（SCN）of hypothalamus in collagen induced arthritis（CIA）rats and the regulation of Tripterygium.Methods:The rat model of collagen induced arthritis was established and randomly divided into a model control group,a prednisone acetate group and a tripterygium glycosides group.There was a blank control group.There were 8 rats in each group.The prednisone acetate group and the tripterygium glycosides group were given intragastric administration at 20:00,respectively with dosage of 1.5 mg·kg^-1·d^-1 and 10.5 mg·kg^-1·d^-1,once a day.The blank control group and the model control group were given normal saline successively for 6 weeks.The paw and joint swelling of rats in each group were observed.ELISA was used to detected the levels of TNF-α,IL-1β and IL-6.The gene and protein expressions of CLOCK and Bmall in SCN were detected by qRT-PCR and Western-blot.Results:①At the end of the experiment,the left posterior ankle joint circumference,plantar thickness,toe volume,arthritis index（AI）scores of CIA model rats were significantly increased compared with the blank control group（P < 0.05）.Levels of TNF-α,IL-1β,IL-6 were significantly increased（P < 0.05）,and the gene and protein expressions of CLOCK and Bmall in SCN significantly decreased（P < 0.05）.②Compared with the model control group,the swelling degree of joint and paw could be significantly improved,the levels of TNF-α,IL-1β and IL-6 decreased and the gene and protein expressions of CLOCK and Bmall in SCN increased in the prednisone acetate group and the tripterygium glycosides group.The regulatory effect of in the tripterygium glycosides group on Bmall expression in SCN was better than that in the prednisone acetate group（P < 0.05）.Conclusion:The pathogenesis of arthritis affects the expression of serum inflammatory cytokines and hypothalamic SCN circadian clock;the mechanism of Tripterygium wilfordii polyglycoside in treating CIA model rats is related to the regulation of hypothalamic SCN core clock gene expression and peripheral inflammatory cytokine secretion level.

　　【Keywords】 collagen induced arthritis;tripterygium glycosides;suprachiasmatic nucleus of hypothalamus;biological clock;Bmall;Clock;rats