Effects of Mingzhu Oral Liquid on the Hypothalamic-Pituitary-Adrenal Axis in Rats with Liver-Kidney Yin Deficiency

摘要

Objective:This study aimed to observe the effects of Mingzhu Oral Liquid on the hypothalamic-pituitary-adrenal(HPA) axis in rats with “liver-kidney yin deficiency”, in order to provide scientific research support for its clinical application in treating related disorders. Methods:A “liver-kidney yin deficiency” model was established in male SpragueDawley(SD) rats using a combination of chronic restraint stress and a single lipopolysaccharide(LPS) challenge. The rats were randomly divided into four groups:a blank control group, a model group, a low-dose Mingzhu Oral Liquid group, and a high-dose Mingzhu Oral Liquid group. The blank control group and model group were given normal saline by gavage, while the treatment groups received respective doses of Mingzhu Oral Liquid. Gavage administration was performed once daily for 30 consecutive days. During this period, all groups except the blank control group were subjected to restraint stress. Following the final gavage, all groups except the blank control received an intraperitoneal injection of LPS. Samples were collected 24 h post-injection. Serum levels of cyclic adenosine monophosphate(cAMP) and cyclic guanosine monophosphate(cGMP) were measured by enzyme-linked immunosorbent assay(ELISA) to evaluate the model state. The serum concentrations of corticotropin-releasing hormone(CRH), adrenocorticotropic hormone(ACTH), and glucocorticoid(GC) were determined to assess HPA axis activity. Changes in proinflammatory factors [tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β)] and the anti-inflammatory factor interleukin-10(IL-10) were also measured. Results: One week into the experiment, the weight gain rate slowed in all stress groups. By the end of the experiment, the body weight of these groups was significantly lower than that of the blank control group. Biochemical and hematological analyses revealed that the model group exhibited a significant decrease in lymphocyte count, an increased cAMP/cGMP ratio, reduced activities of glutathione S-transferase(GST) and glutathione transferase(GLT), elevated levels of blood urea nitrogen(BUN) and serum creatinine(Scr), increased serum contents of TNF-α and IL-1β, and a decreased content of IL-10. These findings confirmed the successful establishment of the rat model. Although the body weight of animals treated with Mingzhu Oral Liquid remained lower than that of the normal group, the treatment improved weight gain compared to the model group. Furthermore, Mingzhu Oral Liquid administration increased lymphocyte count, decreased the cAMP/cGMP ratio, restored GST and GLT activities, reduced BUN and Scr levels, lowered serum TNF-α and IL-1β contents, and increased IL-10 levels, indicating a significant ameliorative effect on the deficiency symptoms. Additionally, serum levels of CRH, ACTH, and GC were elevated in the model rats, suggesting HPA axis hyperactivity. Treatment with Mingzhu Oral Liquid reduced the serum concentrations of these hormones, significantly alleviating the excited state of the HPA axis in stressed rats. Conclusion:Mingzhu Oral Liquid significantly improves the abnormal overall physical signs, blood biochemical parameters, and systemic inflammation in rats with “liver-kidney yin deficiency.” These therapeutic effects may be associated with the corrective action of Mingzhu Oral Liquid on the dysfunctional HPA axis in this model.