scholarly journals Effect of Hirsutella sinensis Fungus on the Hypothalamic-Pituitary-Adrenal Axis in Lewis Rats with Kidney-Yang Deficiency Syndrome

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Lizong Zhang ◽  
Jiali Lang ◽  
Lu Jin ◽  
Lushuai Jin ◽  
Beibei Cao ◽  
...  

Kidney-yang deficiency syndrome (KYDS) is a classic syndrome in traditional Chinese medicine, which is mainly caused by damage to the hypothalamic-pituitary-adrenal (HPA) axis. Hirsutella sinensis fungus (HSF), an artificial substitute of Cordyceps sinensis, has been widely used in TCM. However, the effects and the possible mechanism of HSF on the HPA axis and corresponding KYDS have not yet been investigated. In this study, Lewis rats were used as a spontaneous KYDS model. HSF was intragastrically administered to the Lewis rats at two doses: low dose (1 g/kg) and high dose (2 g/kg). Body weight, temperature, and behavioral tests including grip strength, open field, and Morris water maze (MWM) tests were used to evaluate the KYDS symptoms. Enzyme-linked immunosorbent assay was used to detect the level of circulating adrenocortisol (ACTH), corticosterone (CORT), corticotropin releasing hormone (CRH), cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP). In addition, mRNA expression of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin 10 (IL-10), CRH, glucocorticoid receptor (GR), and mineralocorticoid receptor (MR) was detected by quantitative real-time polymerase chain reaction (Q-PCR). The Lewis rats were indicated to have KYDS symptoms and HSF treatment ameliorated these symptoms via enhancement of the HPA axis function, which was evidenced by the increased levels of CRH, ACTH, and CORT in serum and 17-OHCS in urine. HSF also significantly improved the expression of TNF-α, IFN-γ, and IL-2, secreted by Th1 cells, which might accelerate the activation of the immune system related to the HPA axis function. Thus, we conclude that HSF can alleviate KYDS symptoms in Lewis rats by regulating the HPA axis through accelerated immune system activation.

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Yuntian Shen ◽  
Qiang Zhao ◽  
Jiangbo Wu ◽  
Zhuoran Wang ◽  
Wei Yang

Introduction: Cardiac arrest (CA) is associated with high mortality and morbidity, which is in part due to infectious complications developed in CA patients. Infection complications, particularly pneumonia, occur in approximately 60% of CA patients. Given this high incidence, we hypothesized that after CA, the immune system is impaired, which increases the susceptibility of CA patients to potential infections. Therefore, in this study, we systematically examined the immune response in the brain and peripheral immune organs after CA. Methods: Mice were subjected to CA and cardiopulmonary resuscitation (CA/CPR). Flow cytometry, ELISA, immunohistochemistry, and quantitative PCR were used to analyze the immune response in various post-CA organs. Results: First, we characterized the time course of the immune response in the spleen after CA/CPR. CA/CPR induced significant changes in all major immune cell populations. Notably, B cell frequencies decreased, while T cell frequencies increased, in various organs on day 3 post-CA. Further, the levels of pro-inflammatory cytokines, eg IL-6, were markedly increased in the blood and brain after CA. Critically, we found that the lymphocyte counts in the spleen and thymus were dramatically lower in CA mice than in sham mice. Interestingly, CA/CPR caused progressive atrophy of the spleen and thymus. Since it has been shown that CA/CPR alters activity of the hypothalamic-pituitary-adrenal (HPA) axis, we speculated that CA-induced atrophy of lymphoid organs is mediated by the HPA axis. Thus, we treated CA mice with RU486, a glucocorticoid receptor antagonist. Indeed, this treatment reversed CA-induced organ atrophy and mitigated immune cell depletion, both in the thymus and spleen. Conclusions: We provided for the first time evidence that CA/CPR rapidly induced a systemic inflammatory response followed by impairment of the immune system, which eventually led to a massive loss of immune cells in the peripheral immune organs. This CA-induced immunodeficiency appears to be mediated by dysregulation of the HPA axis. Our findings here may be of high clinical significance, considering the high incidence of infectious complications in CA patients and their detrimental effects on CA outcome.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yijia Zeng ◽  
Tingna Li ◽  
Xiaorui Zhang ◽  
Yuanyuan Ren ◽  
Qinwan Huang ◽  
...  

Objective. Modern research shows that Haima Duobian pill (HDP) can relieve the kidney yang deficiency syndrome (KYDS), but the mechanism is still unclear. The aim of this work was to study the effects of HDP in a rat model of KYDS. Materials and Methods. The network pharmacology methods were used to predict the therapeutic effects of Haima Duobian pill. Adenine was used to establish the rat model of kidney yang deficiency syndrome. The general physical signs of rats were observed after different doses of Haima Duobian pill (HDP) were given. Serum cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2), and gonadotropin-releasing hormone (GnRH) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Then, the histopathologic changes and sperm activity were detected. Results. HDP could improve the general signs of kidney yang deficiency syndrome rats. After the rats were treated with HDP, the expression of cGMP and E2 was significantly inhibited and the expression of cAMP and T was significantly increased. The pathological damage of testis, epididymis, and seminal vesicle was alleviated, and the sperm activity was improved. Conclusion. For adenine-induced kidney yang deficiency syndrome in rats, HDP had a significant therapeutic effect.


2014 ◽  
Vol 307 (11) ◽  
pp. E994-E1008 ◽  
Author(s):  
Irene Cortés-Puch ◽  
Caitlin W. Hicks ◽  
Junfeng Sun ◽  
Steven B. Solomon ◽  
Peter Q. Eichacker ◽  
...  

The clinical significance and even existence of critical illness-related corticosteroid insufficiency is controversial. Here, hypothalamic-pituitary-adrenal (HPA) function was characterized in severe canine Staphylococcus aureus pneumonia. Animals received antibiotics and titrated life-supportive measures. Treatment with dexamethasone, a glucocorticoid, but not desoxycorticosterone, a mineralocorticoid, improves outcome in this model. Total and free cortisol, adrenocorticotropic hormone (ACTH). and aldosterone levels, as well as responses to exogenous ACTH were measured serially. At 10 h after the onset of infection, the acute HPA axis stress response, as measured by cortisol levels, exceeded that seen with high-dose ACTH stimulation but was not predictive of outcome. In contrast to cortisol, aldosterone was largely autonomous from HPA axis control, elevated longer, and more closely associated with survival in early septic shock. Importantly, dexamethasone suppressed cortisol and ACTH levels and restored ACTH responsiveness in survivors. Differing strikingly, nonsurvivors, sepsis-induced hypercortisolemia, and high ACTH levels as well as ACTH hyporesponsiveness were not influenced by dexamethasone. During septic shock, only serial measurements and provocative testing over a well-defined timeline were able to demonstrate a strong relationship between HPA axis function and prognosis. HPA axis unresponsiveness and high aldosterone levels identify a septic shock subpopulation with poor outcomes that may have the greatest potential to benefit from new therapies.


1997 ◽  
Vol 13 (1) ◽  
pp. 57-66 ◽  
Author(s):  
Hector G. Ortega ◽  
Manuel Lopez ◽  
Atsushi Takaki ◽  
Qin-Heng Huang ◽  
Akira Arimura ◽  
...  

The effects of different methylmercury (MeHg) forms on the immune system and the hypothalamic pituitary adrenal (HPA) axis were assessed. The lymphocyte response to Concanavalin A (Con A) stimulation, blood levels of interleukin-6 (IL-6), adrenocorticotrophin hormone (ACTH), and corticosterone in the presence of different MeHg compounds was measured. Rats were exposed to methylmercury sulfide [(MeHg)2S] and methylmercury chloride (MeHgCl) at concentrations of 5 and 500 μg per liter in the drinking water for 8 or 16 weeks. Short-term exposure (8 weeks) at both, low- and high-doses of (MeHg)2S significantly enhanced lymphocyte responsiveness. MeHgCl only induced increased lymphocyte responsiveness at the low-dose exposure. Circulating levels of IL-6 after short-term exposure were increased in the MeHgCl-exposed group. The HPA axis activation was demonstrated by increased levels of ACTH and corticosterone levels. This response was predominant in low-dose exposed animals. Long-term (16 weeks) exposure resulted in a reduction in lymphocyte proliferation after both low- and high-dose MeHgCl exposures. The (MeHg)2S exposure resulted in a 3-fold increase in the proliferative response. Levels of ACTH were elevated 3-fold in the (MeHg)2S-exposed group, and no increase of corticosterone was observed in the high-dose exposed group at 8 weeks, no effect of(MeHg)2S was observed at 16 weeks. The MeHgCl exposed group showed an increase in ACTH and corticosterone levels at 8 weeks; this response was not observed at 16 weeks. These data indicate that exposure to MeHg compounds enhances T-cell proliferation in most of the cases, in a dose- and time-dependent fashion. Release of IL-6 also depends on the length of exposure. Early increases in circulating ACTH at 8 weeks also suggest activation of the HPA axis. This may contribute to the production of IL-6 and surveillance of regulatory homeostatic responses against environmental agents that mimic stress-like responses.


Author(s):  
Andreas Menke ◽  
Felix Nitschke ◽  
Anna Hellmuth ◽  
Jacqueline Helmel ◽  
Catherina Wurst ◽  
...  

2021 ◽  
Vol 9 ◽  
Author(s):  
Cynthia R. Rovnaghi ◽  
Joseph Rigdon ◽  
Jean-Michel Roué ◽  
Monica O. Ruiz ◽  
Victor G. Carrion ◽  
...  

The objective of this study was to examine if longitudinal trajectories of hair cortisol concentrations (HCC) measured at two or three yearly time points can identify 1-3 year old children at risk for altered hypothalamic-pituitary-adrenal (HPA)-axis function due to early life stress (ELS). HCC was measured (N = 575) in 265 children using a validated enzyme-linked immunosorbent assay. Hair was sampled in Clinic Visits (CV) centered at years 1, 2, and 3 (n = 45); 1 and 2 (n = 98); 1 and 3 (n = 27); 2 and 3 (n = 95). Log-transformed HCC values were partitioned using latent class mixed models (LCMM) to minimize the Bayesian Information Criterion. Multivariable linear mixed effects models for ln-HCC as a function of fixed effects for age in months and random effects for participants (to account for repeated measures) were generated to identify the factors associated with class membership. Children in Class 1 (n = 69; 9% Black) evidenced declining ln-HCC across early childhood, whereas Class 2 members (n = 196; 43% Black) showed mixed trajectories. LCMM with only Class 2 members revealed Class 2A (n = 17, 82% Black) with sustained high ln-HCC and Class 2B (n = 179, 40% Blacks) with mixed ln-HCC profiles. Another LCMM limited to only Class 2B members revealed Class 2B1 (n = 65, 57% Black) with declining ln-HCC values (at higher ranges than Class 1), and Class 2B2 (n = 113, 30% Black) with sustained high ln-HCC values. Class 1 may represent hair cortisol trajectories associated with adaptive HPA-axis profiles, whereas 2A, 2B1, and 2B2 may represent allostatic load with dysregulated profiles of HPA-axis function in response to varying exposures to ELS. Sequential longitudinal hair cortisol measurements revealed the allostatic load associated with ELS and the potential for developing maladaptive or dysregulated HPA-axis function in early childhood.


2017 ◽  
Vol 5 ◽  
pp. 1028-1031
Author(s):  
SongĂĽl ĂśnĂĽvar ◽  
Zübeyde Tanrıverdi

Background: Recurrent miscarriages are common complications in pregnancy. Neopterin is one of the immunologic biomarkers of several diseases related to activation of the cellular immune system. RSA is associated with immune system related abnormalities.Objectives: We aimed to investigate the effectiveness of neopterin levels in the early diagnosis of RSA.Methods: Eighty RSA patients and forty-three healthy controls were included in the study. The neopterin concentrations were determined by the enzyme-linked immunosorbent assay (ELISA) method. For the statistical analysis, Mann-Whitney U test and Pearson correlation test were used the; p<0.05 was considered statistically significant.Results: Serum mean neopterin levels were 16.47±0.095 nmol/L in RSA group and 6.14±0.041 nmol/L in control group, respectively. Compared to the control group, a statistically significant increase (p=0.0183) in the serum neopterin levels of the patients was observed. There was a negative correlation between serum neopterin level and age in both the control (R=0.0774, p=0.6236) and RSA groups (R=0.1415, p=0.2089). However, this correlation was not statistically significant (p>0.05).Conclusions: With overstimulation of interferon-γ (INF-γ) during pregnancy, the production of neopterin increases by monocytes/macrophages. The measurement of neopterin levels in the serum contributes to the early diagnosis of pregnancy losses.


2020 ◽  
Author(s):  
Fan-Song Mu ◽  
Min Chen ◽  
Meng-Fei Tian ◽  
Chang-Yin Feng ◽  
Xian-Ming Meng ◽  
...  

Abstract Background Boschniakia rossica (Cham. & Schltdl.) B. Fedtsch. (Bu-Lao-Cao in Chinese name) is a famous Chinese traditional drug and mainly distributed in Korea, Japan, Russia, and China. The dried whole grass of Boschniakia rossica is commonly used in traditional Chinese medicine to treat kidney deficiency, yang deficiency, waist and knee aches and constipation. In order to quantify the active ingredients in B. rossica chinensis and body weight, clinical features and serum SOD and MDA activities, cAMP, cGMP, and testosterone (T), follicle-stimulating growth hormone (FSH), mouse bone morphogenetic protein-5 (BMP-5), mouse activin receptor IIA (ActRIIA) were measured to elucidate the mechanism underlying its treatment of kidney yang deficiency potential. Methods Extracts of B. rossica were evaluated by HPLC-MS analyses. Kidney-yang deficiency syndrome was induced in mouse with hydrocortisone (10 mg/Kg, 15d) and treated with B. rossica extract. The animals were treated orally with 3 doses of B. rossica extract: 1000, 500 and 250 mg/Kg, for 15 days. Body weight and clinical characteristics were recorded daily. For biochemical analyses, the following tests were performed: superoxide dismutase (SOD) activity, malondialdehyde (MDA) activity, testosterone (T) content, follicle growth hormone (FSH) content, cyclic adenosine monophosphate (cAMP) content, mouse bone morphogenetic protein-5 (BMP-5) content and activin receptor IIA (ActRIIA) content. Results Our study found that all the mice except the blank group showed significant systemic depletion caused by hydrocortisone. Low T content, low cAMP activity and high cGMP content were consistent with the physiological and biochemical indexes of kidney-yang deficiency syndrome. After oral gavage, the pathological conditions were improved in both the Positive group and the B. rossica groups.Conclusions The high-dose extract of B. rossica showed similar therapeutic effects as Jingui Shenqi Pill. The extract of B. rossica can be used to treat with hydrocortisone-induced kidney yang deficiency syndrome by increasing serum testosterone content and decreasing FSH content. More importantly, the experiment found that activin A and BMP-5 also have effects on kidney yang deficiency syndrome.


2020 ◽  
Author(s):  
Yehui Zhang ◽  
Junfeng Tong ◽  
Yan Zhu ◽  
Qihan Luo ◽  
Hongxia Yu ◽  
...  

Abstract Objective: The paper is aimed to establish a method for renal injury in rats with kidney yang deficiency syndrome (KYDS) of the stable by comparing different model establishment methods and optimize the final modeling method.Method: In order to mimic water metabolism disorder of KYDS- a diagnostic pattern in traditional Chinese medicine (TCM), we made a comparison of hydrocortisone-induced, adenine-induced, dexamethasone combined with adriamycin-induced KYDS rat model according to testing general behavior, detecting Hypothalamus-pituitary-adrenal (HPA) axis function and renal function also making use of drug action. Additionally, the effect of adenine at a dose of 100 mg/kg, 150 mg/kg, and 200 mg/kg, respectively, on establishment of KYDS model was investigated in rats. Finally, Shenqi Wan (SQW, 3 g/kg) was used to estimate the deterioration of adenine that is associated with KYDS. Result: Three KYDS model rats all exhibited weight loss, anal temperature drop, reduced food intake and dysfunction of the Hypothalamus-pituitary-adrenal (HPA) axis, which could be alleviated by SQW. However, different from other two methods, adenine-induced rats were prominently manifested as water and fluid metabolism disorders (sharply increased water intake and urine volume). Renal injury in adenine-induced rats was more obvious than it in hydrocortisone-induced rats and dexamethasone combined with adriamycin-induced rats. And renal toxicity caused by adenine was reversible by SQW treatment. Water metabolism disorder in adenine-induced rats was more closer to clinical symptoms of patients with KYDS. Subsequently, we found different dose of adenine gavage (100, 150, 200 mg/kg) for 14 days result in general behavior change, dysfunction of HPA axis and renal function damage. But only medium-dose of adenine induced toxicity could be reversed by SQW treatment for 21 days.Conclusion: The result of the comparison between the three modeling methods showed that adenine-induced was more effective to establish the KYDS model, and only a medium-dose of adenine for inducing renal poison could be recovered by SQW treatment. Therefore, a medium-dose of adenine was optimal for the establishment of the KYDS rat model.Trial registration : This is an animal experiment, trial registration is not necessary.


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