氯沙坦对癫痫大鼠转化生长因子-β信号通路的影响  

Effect of Losartan on Transforming Growth Factor-β Signaling Pathway in Epileptic Rats

作　　者：潘学威 张晓光 朱思亮 郑建乐 金洁 蒋艳艳 Pan Xuewei;Zhang Xiaoguang;Zhu Siliang;Zheng Jianle;Jin Jie;Jiang Yanyan(Department of Neurology, Wenzhou CentralHospital, Zhejiang Wenzhou 325000, China;Department of Neurology, the Second Affiliated Hospital of Wenzhou Medical University)

机构地区：[1]温州市中心医院神经内科,浙江温州325000 [2]温州医科大学附属第二医院神经内科

出　　处：《中国药师》2019年第4期640-644,共5页China Pharmacist

摘　　要：目的:探讨氯沙坦对癫痫大鼠转化生长因子-β(TGF-β)信号通路的影响。方法:选取建模成功的大鼠75只,随机分为5组,每组15只,分别为:模型对照组、拉莫三嗪组(25 mg·kg^(-1)·d^(-1))、氯沙坦低(15 mg·kg^(-1)·d^(-1))、中(30 mg·kg^(-1)·d^(-1))、高(45 mg·kg^(-1)·d^(-1))剂量组,另取未建模大鼠15只为空白对照组。各给药组灌胃给予相应药物,空白对照组及模型对照组给予等体积生理盐水,持续给药11 d。观察各组癫痫大鼠一般情况与行为变化,利用实时荧光定量和蛋白免疫印迹检测TGF-β、Smad7、p-Smad2/3、Smad4的转录和翻译水平。结果:与空白对照组相比,模型对照组大鼠精神萎靡,皮毛脏乱,饮食量下降,体质量增加量显著减少(P<0.05);TGF-β、p-Smad2/3、Smad4的表达量显著升高,Smad7的表达量显著降低(P<0.05)。与模型对照组相比,氯沙坦干预组大鼠一般情况明显得到改善,体质量增加量显著上升(P<0.05);大鼠癫痫发作级别显著降低(P<0.05);TGF-β、p-Smad2/3、Smad4的表达量显著降低,Smad7的表达量显著升高(P<0.05),且呈剂量依赖性。氯沙坦中、低剂量组的以上各指标均与拉莫三嗪组差异有统计学意义(P<0.05)。结论:氯沙坦可能通过调节TGFβ/Smads信号通路参与控制大鼠癫痫发作。Objective: To investigate the effect of losartan on transforming growth factor-β( TGF-β) signaling pathway in epileptic rats. Methods: Totally 75 rats were randomly divided into 5 groups: the model control group,lamotrigine group( 25 mg · kg^-1·d^-1),losartan low( 15 mg·kg^-1·d^-1),medium( 30 mg·kg^-1·d^-1) and high( 45 mg·kg^-1·d^-1) dose groups,and another15 rats without modelling were taken as the blank control group. Each group was given corresponding drug by intragastric administration and the blank control group and the model control group were given equal volume of physiological saline for 11 days. The general situation and behavior of rats were observed,and the levels of transcription and translation of TGF-β,Smad7,p-Smad2/3 and Smad4 were detected by qRT-PCR and Western blot. Results: Compared with the blank control group,the rats in the model control group were mentally depressed with dirty fur,decreased diet and decreased weight gain( P < 0. 05),the expressions of TGF-β,p-Smad2/3 and Smad4 increased significantly,and the expression of Smad7 decreased significantly( P < 0. 05). Compared with the model control group,the rats in losartan intervention groups were with generally improved situation,and the weight gain increased significantly( P <0. 05),the level of epileptic seizure was decreased significantly( P < 0. 05),the expressions of TGF-β,p-Smad2/3 and Smad4 were significantly decreased,and the expression of Smad7 was increased significantly( P < 0. 05). The effects of losartan on epileptic rats were dose-dependent. There were significant differences in the above indices between losartan low and medium dose groups and lamotrigine group( P < 0. 05). Conclusion: Losartan may participate in the control of seizures in rats by regulating TGFβ/Smads signaling pathway.

关 键 词：氯沙坦 癫痫大鼠 TGFβ/Smads信号通路 SMAD7 P-SMAD2/3 Smad4 

分 类 号：R965.1[医药卫生—药理学]