Effects of Rhubarb on the Expression of Glucocorticoids Receptor and Regulation of Cellular Immunity in Burn-Induced Septic Rats
Glucocorticoids (GC) are essential anti-inflammatory corticoids in the human body, playing a crucial role in protecting the body from insults under various stresses such as infection, trauma, and hemorrhage. The biological effects of GC are primarily mediated through the specific glucocorticoid receptor (GR). GR is a transcriptional regulator with a modular structure, consisting of several domains, including the ligand-binding domain where glucocorticoids bind. Before binding to GC, the majority of GR is localized in the cytosol and associated with the heat shock protein 90 (hsp90)-containing chaperone complex. Upon binding to GC, GR dissociates from the chaperone proteins, exposes nuclear localization sequences, and associates with genomic glucocorticoid response elements (GREs) to regulate the transcriptional rate of nearby genes. GR interacts with various proteins, such as transcription factors, cofactors, and modifying enzymes, making its anti-inflammatory capacity a critical action.
CD4+, CD8+, CD4+CD25+ T cells, CD19+ B cells, and natural killer (NK) cells play an important role in the elimination of infecting pathogens. CD4+ and CD8+ are the major T cell subsets, with CD4+ T cells playing a critical role in innate and adaptive immune systems, and CD8+ T cells being important for the targeted killing of virus-infected cells. NK cells are responsible for initiating inflammatory events and inducing widespread lymphocyte apoptosis. Therefore, T cells and NK cells play a critical role in protecting the host against life-threatening infections. Patients with impaired host immune cells are unable to eradicate primary infections and are also susceptible to secondary infections during sepsis.
Recent studies have highlighted the role of immune dysfunction in septic patients. Therefore, modulating the expression of GR in stress and maintaining immune homeostasis during sepsis is crucial. Some traditional Chinese medicines, such as rhubarb, have shown potential effects on anti-inflammatory and immune modulation. This study aimed to investigate the effects of rhubarb on the binding activity of GR in liver cytosol, the binding capacity of GR in peripheral blood leukocytes, and the percentages of CD4+, CD8+, CD4+CD25+ T cells, CD19+ B cells, and NK cells in the lymphocytes in peripheral blood using a burn-induced septic rat model.
The study involved 66 healthy male Sprague Dawley (SD) rats, randomized into sepsis group (n=24), rhubarb group (n=24), and control group (n=18). Each group was further divided into 12, 24, and 72-hour subgroups based on different time points. The sepsis rat model was established by intraperitoneal injection of endotoxin O111:B4 after a 30% body surface area III degree burn injury. The rhubarb group received 50 mg/kg rhubarb powder dissolved in 1 mL saline through a gastric tube, while the sepsis and control groups received saline. The binding activity of GR in liver cytosol and the binding capacity of GR in peripheral blood leukocytes were analyzed using radiation ligand binding assays. The percentages of CD4+, CD8+, CD4+CD25+ T cells, CD19+ B cells, and NK cells in peripheral blood lymphocytes were detected using flow cytometry.
The results showed that the binding activity of GR in liver cytosol and the binding capacity of GR in peripheral blood leukocytes were significantly decreased in a time-dependent manner in the sepsis group. However, these parameters were increased in a time-dependent manner after rhubarb administration. Twelve hours after sepsis, the percentages of CD4+ T cells, CD4+/CD25+ T cell ratio, and CD19+ B cells in peripheral blood were significantly increased in the sepsis group, while the percentage of NK cells was significantly decreased. The percentage of CD8+ T cells was significantly decreased in the sepsis group but significantly increased in the rhubarb group. Seventy-two hours after sepsis, the ratio of CD4+/CD25+ T cells in peripheral blood was significantly increased in the sepsis group but significantly decreased in the rhubarb group. Furthermore, the percentages of CD19+ B cells in peripheral blood were significantly decreased at 72 hours in the rhubarb group.
The study concluded that rhubarb might play potential anti-inflammatory and immunomodulatory roles in the sepsis process. The findings suggest that rhubarb could modulate the expression of GR and regulate cellular immunity in burn-induced septic rats, providing a new perspective on the treatment of sepsis using traditional Chinese medicine.
The morbidity and mortality of sepsis are extremely high in intensive care units (ICUs), and the immune response plays a crucial role in the occurrence and progression of sepsis. Previous studies have indicated that rhubarb could reduce the expression and concentration of TNF-α in plasma and liver, thereby inhibiting the severity of inflammation. The current study observed the effect of rhubarb on immune response in a sepsis rat model in vivo. However, the relationship between GR expression and cellular immunity dysfunctions and the mechanism of rhubarb regulating GR expression in cell immunity regulation need further exploration.
The study was supported by a grant from the National Natural Science Foundation of China. The findings contribute to the growing body of evidence on the anti-inflammatory and immunoregulatory effects of rhubarb, offering a new method for the treatment of sepsis. However, the study has some limitations, including the lack of survival rate data for the sepsis and rhubarb groups, the insufficient number of rats in each group, and the detection of only partial indicators of innate immunity.
In summary, this study provides valuable insights into the effects of rhubarb on the expression of glucocorticoid receptors and the regulation of cellular immunity in burn-induced septic rats. The results highlight the potential of rhubarb as a therapeutic agent for sepsis, emphasizing the need for further research to fully understand its mechanisms of action and optimize its use in clinical settings.
doi.org/10.1097/CM9.0000000000000201
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