基于胸腺微环境变化的补肾填精法对先天肾虚仔鼠T细胞发育的影响

Exploring the effect of tonifying kidney and replenishing essence method on the development of T cells via the changes of thymus microenvironment in neonatal rats with congenital kidney deficiency

目的通过构建先天肾虚仔鼠模型并给予左归丸干预来探讨先天肾虚对胸腺微环境和T细胞发育的影响,并论证补肾填精法的作用。方法孕鼠分为正常组、模型组和补肾组。正常组孕鼠不做任何处理;模型组孕鼠采用复合应激法刺激造模;补肾组孕鼠造模的同时给予左归丸灌胃处理。正常组孕鼠和模型组孕鼠给予生理盐水灌胃处理。仔鼠出生后,对比分析各组仔鼠的情况并观察胸腺形态和超微结构。进一步检测仔鼠胸腺中Caspase-8、IL-2、IL-7、IL-15及CD3+T细胞和CD4+T细胞的表达情况。结果模型组仔鼠胸腺形态和超微结构发生改变,Caspase-8、IL-2和IL-15的表达增加,IL-7的表达减少,CD3+T细胞和CD4+T细胞数量减少。左归丸干预能够有效逆转上述变化。结论先天肾虚会破坏仔鼠的胸腺微环境,进而影响T细胞的发育,而左归丸通过补肾填精法调节Caspase-8、IL-2、IL-15和IL-7的变化,可以改善其胸腺微环境和促进其T细胞的发育。

Objective To explore the effect of congenital kidney deficiency on the thymus microenvironment and the development of T cells and further demonstrate the effect of tonifying kidney and replenishing essence method via constructing a model of congenital kidney deficiency and intervening with Zuogui Wan in neonatal rats. Methods Pregnant rats were divided into normal group, model group and kidney-tonifying group. The pregnant rats in normal group were not treated. The pregnant rats in model group were treated by compound stress method. Zuogui Wan was administered intragastrically to the pregnant rats in kidney-tonifying group during the process of modeling. Normal saline was administered intragastrically to the pregnant rats in normal group and model group. After the neonatal rats were born, contrastive analysis was performed to analyze the situation of the neonatal rats in each group, and morphological and ultrastructural changes of thymus were observed in neonatal rats of each group. Furthermore, the expression levels of Caspase-8, IL-2, IL-7, IL-15, CD3+ T cells and CD4+ T cells were detected in neonatal rats of each group. Results The morphology and ultrastructure of thymus in neonatal rats of model group were changed, the expression levels of Caspase-8, IL-2 and IL-15 increased, the expression level of IL-7 decreased and the number of CD3+ T cells and CD4+ T cells decreased. Zuogui Wan intervention effectively reversed the above changes. Conclusion Congenital renal asthenia damages the thymus microenvironment and thus influences the development of T cells in neonatal rats, while Zuogui Wan regulates the changes of Caspase-8, IL-2, IL-15 and IL-7 via tonifying kidney and replenishing essence method, which can improve the status of thymic microenvironment and promote the development of T cells in neonatal rats with congenital renal asthenia.