加味四君子汤通过mTOR信号通路延缓小鼠脾脏组织衰老

Jiawei Sijunzi decoction delays aging of mouse spleen tissue through mTOR signaling pathway

目的探讨加味四君子汤延缓小鼠脾脏组织衰老作用及其可能机制。方法将40只8周龄雄性昆明小鼠随机分为加味四君子汤低剂量组、加味四君子汤高剂量组、模型组和对照组,每组10只。加味四君子汤低剂量组、加味四君子汤高剂量组和模型组小鼠通过腹腔注射0.2 g/kg D-半乳糖溶液建立衰老模型,加味四君子汤低剂量组和高剂量组分别予以加味四君子汤1.6、6.4 g/kg,模型组及对照组每天予等体积生理盐水,连续灌胃给药42 d。观察小鼠脾脏组织病理变化,计算脾脏指数,检测血清Ig G水平,采用q RT-PCR检测脾脏组织中哺乳动物雷帕霉素靶蛋白(m TOR)信号通路相关因子磷脂酰肌醇3-激酶(PI3K)、p70核糖体蛋白S6激酶(p70S6K)和真核细胞翻译起始因子4E结合蛋白1(4E-BP1)m RNA表达水平。结果模型组小鼠脾脏组织发生明显病理改变,脾脏指数和血清Ig G水平较对照组均下降(P均<0.05),脾脏组织中PI3K、p70S6K m RNA表达水平较对照组均升高(P均<0.05)。加味四君子汤高剂量组和低剂量组脾脏组织形态病理改变程度较模型组轻,加味四君子汤高剂量组脾脏指数、血清Ig G水平均高于模型组(P均<0.05),且加味四君子汤低剂量组和高剂量组脾脏组织中PI3K、p70S6K mRNA表达水平均低于模型组(P均<0.05)。结论加味四君子汤能够改善小鼠脾脏组织衰老性退化,其机制可能与抑制m TOR信号通路有关。

Objective To investigate the role of Jiawei Sijunzi decoction(JSD)in delaying aging of mouse spleen tissue and its possible mechanism.Methods Forty 8-week-old male Kunming mice were evenly randomized into low-dose group,high-dose group,model group and control group(n=10).The aging models were established by intraperitoneal injection of 0.2 g/kg D-galactose in the low-dose,high-dose and model groups.The low-dose and high-dose groups were given JSD 1.6 and 6.4 g/kg by gavage,respectively,and the model group and control group were given the same volume of normal saline for 42 consecutive days.The pathological changes of the spleen tissue were observed,the spleen index was calculated,and the serum immunoglobulin G(IgG)level was detected.The mRNA expression levels of phosphatidylinositol 3-kinase(PI3 K),p70 ribosomal protein S6 kinase(P70 S6 K)and eukaryotic translation initiation factor 4 E binding protein 1(4 E-BP1)of mammalian target of rapamycin(mTOR)signaling pathway were detected by quantitative real-time polymerase reaction(qRT-PCR).Results With obvious pathological changes,the spleen index and the serum IgG level of the model group were significantly lower than those of the control group(all P<0.05),while the mRNA expression levels of PI3 K and P70 S6 K in spleen tissue were significantly higher than those in the control group(all P<0.05).The pathological changes of the spleen tissue in the high-dose and low-dose groups were lighter than those in the model group,the spleen index and the serum IgG level in the high-dose group were significantly higher than those in the model group(all P<0.05),while the mRNA expression levels of PI3 K and P70 S6 K in the spleen tissue of the low-dose and high-dose groups were significantly lower than those of the model group(all P<0.05).Conclusion JSD can improve the aging degeneration of spleen tissue in mice,and the mechanism may be related to the inhibition of mTOR signal pathway.