【摘要】 目的基于Wnt/β-catenin信号通路探讨白芍总苷(TGP)对多发性硬化(MS)模型大鼠神经系统的保护作用。方法将60只SD雌性大鼠随机分为对照组、模型组、低剂量组、高剂量组,每组各15只,足跖皮下注射抗原乳剂(豚鼠脊髓匀浆抗原与福氏佐剂)构建MS大鼠模型,对照组给予等体积的生理盐水灌胃;低剂量组和高剂量组则在抗原乳剂注射后分别灌胃给予25、50 mg/kg的TGP,连续给药14 d,对照组和模型组给予等量生理盐水;观察大鼠临床发病、体重变化与神经功能评分情况,HE染色观察大鼠脊髓组织病理变化,TUNEL法观察神经细胞凋亡,Western blot检测Wnt3α,GSK-3β,β-catenin,Bax和Bcl-2蛋白的表达水平。结果模型组和低、高剂量组大鼠体重明显低于对照组;模型组第8 d开始体重明显低于其它3组(P<0.05);低剂量组第12 d开始体重明显低于高剂量组(P<0.05)。与对照组比较,模型组大鼠神经功能评分、细胞凋亡指数(Apoptosis index,AI)、Wnt3α,β-catenin水平明显升高,Bcl-2/Bax,GSK-3β水平明显降低(P均<0.05);与模型组比较,低、高剂量组神经功能评分、AI数值、Wnt3α,β-catenin水平明显降低,Bcl-2/Bax,GSK-3β水平明显升高(P均<0.05),且高剂量组较低剂量组变化更明显(P<0.05)。结论 TGP可能通过抑制Wnt/β-catenin信号通路的激活来发挥对MS模型大鼠神经系统的保护作用。更多还原

【Abstract】 Objective To investigate the protective effect of total glucosides of paeony（TGP） on the nervous system of multiple sclerosis（MS） rats based on Wnt/β-catenin signaling pathway. Methods 60 SD female rats were randomly divided into four groups: control group, model group, low-dose group and high-dose group. Antigen emulsion（guinea pig spinal cord homogenate antigen and Freund’s adjuvant） was injected subcutaneously into the foot and metatarsal to construct MS rat model. The control group was given the same volume of normal saline by gavage. The low-dose group and the high-dose group were given 25 and 50 mg/kg TGP by gavage respectively after the injection of antigen emulsion The control group and the model group were given the same amount of saline for 14 days. The clinical pathogenesis, weight change and neurological score of rats were observed. The pathological changes of spinal cord were observed by HE staining. The apoptosis of neural cells was observed by TUNEL method. The Wnt3α, GSK-3β, β-Catenin, Bax and Bcl-2 protein expression levels were detected by Western blot. Results The weights of rats in model group and low and high dose group were significantly lower than those in control group. From 8^th day, the body weight of model group was significantly lower than that of other 3 group（P<0.05）. From 12^th day, the body weight of the low-dose group was significantly lower than that of the high-dose group（P<0.05）. Compared with the control group, the nerve function score, AI value, Wnt3α, β-catenin levels in the model group were significantly increased, while Bcl-2/Bax and the GSK-3 level was significantly decreased（all P<0.05）. Compared with the model group, the nerve function score, AI value, Wnt3α, β-catenin levels in the low and high dose groups were significantly decreased, while Bcl-2/Bax and the GSK-3 level was significantly increased（all P<0.05）, and the changes of those parameter levels in the high dose group were more significant than those in the low dose group（P<0.05）.Conclusion TGP might play the protective role in the nervous system of MS rats by inhibiting the activation of Wnt/β-catenin signaling pathway.更多还原