加味四君子汤通过mTOR信号通路延缓小鼠脾脏组织衰老

目的 研究加味四君子汤通过mTOR信号通路延缓小鼠脾脏组织衰老作用及其可能机制。方法 将40只8周龄小鼠随机分为对照组、模型组、低剂量组和高剂量组，除对照组外，其余三组小鼠分别予以腹腔注射D-半乳糖形成衰老模型，对照组和模型组予以生理盐水灌胃，同时低剂量组和高剂量组予以加味四君子汤灌胃给药，喂养42天称重后处死小鼠，计算小鼠的脾脏指数；观察血清免疫球蛋白(IgG)水平；观察脾脏组织病理变化；同时采取分子生物学方法检测mTOR信号通路负反馈因子PI3K和下游效应蛋白p70S6K和4E-BP1表达水平，并对其进行统计学分析。结果 与模型组相比，高剂量组脾脏的组织形态衰老程度较模型组低，且脾脏指数、血清IgG显著升高(P<0.05)，低剂量组无明显差别（P＞0.05），且高、低剂量组脾脏组织中PI3K、p70S6K表达水平均下降(P<0.05)，而4E-BP1的表达水平无差别（P＞0.05）。结论 加味四君子汤能改善衰老小鼠脾脏组织形态，提高IgG水平，通过增强机体的免疫力来延缓衰老，其机制可能为减少PI3K的活化抑制mTOR 信号通路，减少p70S6K的表达水平。

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

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 (PI3K), p70 ribosomal protein S6 kinase (P70S6K) and eukaryotic translation initiation factor 4E binding protein 1 (4E-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 PI3K and P70S6K 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 PI3K and P70S6K 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.