Establishment and Comparison of an Experimental Kidney Yang Deficiency Syndrome Rat Model Caused by Hydrocortisone, Adenine, and Dexamethasone Combined with Adriamycin in Rats

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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Effects of Haima Duobian Pill in a Rat Model of Kidney Yang Deficiency Syndrome

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6696234 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Yijia Zeng ◽

Tingna Li ◽

Xiaorui Zhang ◽

Yuanyuan Ren ◽

Qinwan Huang ◽

...

Keyword(s):

Rat Model ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Cyclic Guanosine Monophosphate ◽

Deficiency Syndrome ◽

Guanosine Monophosphate ◽

Network Pharmacology ◽

Enzyme Linked Immunosorbent Assay ◽

Therapeutic Effects ◽

Kidney Yang Deficiency

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.

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Analysis of gene expression and functional changes of adrenal gland in a rat model of kidney yang deficiency syndrome treated with Sini decoction

Experimental and Therapeutic Medicine ◽

10.3892/etm.2018.6521 ◽

2018 ◽

Cited By ~ 2

Author(s):

Nong Tang ◽

Lihong Liu ◽

Hua Qiu ◽

Wei Shi ◽

Dewen Mao

Keyword(s):

Gene Expression ◽

Adrenal Gland ◽

Rat Model ◽

Deficiency Syndrome ◽

Functional Changes ◽

Kidney Yang Deficiency

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Abstract P551: Platelet Activation is Associated with Pulmonary Edema and Renal Injury in a Rat Model of Polymicrobial Sepsis

Hypertension ◽

10.1161/hyp.70.suppl_1.p551 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Jeanne Ishimwe ◽

Maggie L McCalmon ◽

Corbin A Shields ◽

Ashley Gnam ◽

Jan M Williams ◽

...

Keyword(s):

Renal Function ◽

Pulmonary Edema ◽

Organ Dysfunction ◽

Platelet Activation ◽

Rat Model ◽

Renal Injury ◽

Cecal Ligation ◽

Cecal Ligation And Puncture ◽

Activated Platelets ◽

Underlying Mechanisms

Sepsis, life-threatening organ dysfunction due to a dysregulated host response to infection, is positively correlated with platelet activation. Furthermore, clinical studies have also shown that platelet activation is associated with sepsis severity, suggesting a role for platelets in sepsis pathophysiology. Despite this correlation, the underlying mechanisms by which activated platelets contribute to sepsis are under investigated. In preliminary studies, we set out to determine if platelet activation is associated with multi-organ dysfunction and injury in a rat model of chronic polymicrobial abdominal sepsis. Sepsis was induced via cecal ligation and puncture (CLP) followed by cecum removal 24 hours post-CLP. At 72 hours post-CLP, blood, urine, and tissues were collected for analysis. Platelet activation was measured via flow cytometry. Lung wet/dry ratio and plasma creatinine were measured to assess lung edema and renal injury, respectively. Platelet activation doubled in CLP rats versus Sham rats. Activated platelets increased from 3.8±1.7% of the gated population in Sham animals (n=5) to 9.2±1.9% of the gated population in CLP animals (n=5; p=0.07). Lung wet/dry ratio significantly increased from 3.9±0.2 in Sham (n=8) to 6.7±1 in CLP rats (n=8; p<0.05). Furthermore, plasma creatinine increased by 33% from 0.55±0.3 mg/dL in Sham animals (n=6) to 0.73±0.06 mg/dL in CLP rats (n=8; p<0.05), indicating a decrease in renal function. These data demonstrate, for the first time, an increase in platelet activation in response to CLP, and identifies an association of activated platelets with pulmonary edema and reduced renal function in the cecal ligation and puncture rat model of abdominal polymicrobial sepsis. Future studies will investigate the underlying mechanisms by which activated platelets contribute to multi-organ dysfunction and injury in sepsis.

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A New Model of Diarrhea with Spleen-Kidney Yang Deficiency Syndrome

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/4280343 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Jiajie Zhu ◽

Shan Liu ◽

Yu Guo ◽

Liwei Hou ◽

Xiaolan Su ◽

...

Keyword(s):

Body Weight ◽

Grip Strength ◽

Food Consumption ◽

Water Intake ◽

Rat Model ◽

Deficiency Syndrome ◽

Absorption Test ◽

Kidney Yang Deficiency ◽

Defecation Frequency ◽

Forelimb Grip Strength

Objective. The aim of this study was to examine a new method to create a rat model of diarrhea with spleen-kidney yang deficiency syndrome. Methods. A senna leaf (Folium sennae) decoction was made in 3 concentrations of 1.0, 0.5, and 0.25 g/mL. Rats were randomly divided into 4 groups: the control (C)-, high (H)-, middle (M)-, and low (L)- dose groups. The groups received saline, 1.0, 0.5, or 0.25 g/mL senna leaf decoction, respectively, for 4 weeks. Body weight monitoring, food consumption, water intake, defecation frequency, stool Bristol score, weight-loaded forced swimming test, forelimb grip strength test, D-xylose absorption test, serum cortisone, adrenocorticotropic hormone (ACTH), 24 h urine 17-hydroxycorticosteroid (17-OHCS), and histopathological detection were conducted to assess the success of the senna leaf decoction-induced model. Results. This study showed that the senna leaf decoction could induce diarrhea and dose-dependently slow body weight growth, reduce food consumption, and increase water intake, stool Bristol score, and defecation frequency. Statistical differences were found between groups H and M in rectal temperature, weight-loaded forced swimming time, forelimb grip strength, and serum cortisone. The D-xylose absorption test also showed dysfunction of intestinal absorption in groups H and M. The serum cortisone and 24 h urine 17-OHCS were significantly reduced in group H. Conclusions. Gastric gavage of 10 mL/kg of body weight of a high concentration of a senna leaf decoction (1.0 g/mL) for 4 weeks was used to create a rat model of diarrhea with spleen-kidney yang deficiency syndrome.

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/5952612 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Lizong Zhang ◽

Jiali Lang ◽

Lu Jin ◽

Lushuai Jin ◽

Beibei Cao ◽

...

Keyword(s):

Immune System ◽

Hpa Axis ◽

Deficiency Syndrome ◽

Cordyceps Sinensis ◽

Enzyme Linked Immunosorbent Assay ◽

High Dose ◽

Lewis Rats ◽

Hypothalamic Pituitary Adrenal ◽

Immune System Activation ◽

Kidney Yang Deficiency

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.

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