scholarly journals Ghrelin attenuates avascular necrosis of the femoral head induced by steroids in rabbits

2020 ◽  
Vol 19 (10) ◽  
pp. 2097-2101
Author(s):  
Laigang Huang ◽  
Fanshuo Zeng ◽  
Baojuan Cui ◽  
Daoqing Wang ◽  
Min Sun ◽  
...  
Keyword(s):  
Femoral Head ◽  
Avascular Necrosis ◽  
Rabbit Model ◽  
Underlying Mechanism ◽  
Bone Morphogenetic Protein 2 ◽  
Vehicle Group ◽  
Control Group ◽  
Mrna Levels ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue

Purpose: Ghrelin is an endogenous ligand for growth hormone secretagogue receptor. The current study was aimed at examining the effect of ghrelin on avascular necrosis of the femoral head (ANFH) induced by steroids in a rabbit model and also exploring the underlying mechanism. Methods: Experimental rabbits were separated into three groups: Control, Vehicle and Ghrelin. We established a steroid-induced ANFH model in rabbits. Then, MRI scanning and hematoxylin-eosin staining (HE) were conducted to see ANFH. The mRNA levels of Vascular Endothelial Growth Factor (VEGF) and Bone Morphogenetic Protein 2 (BMP-2) were evaluated using real-time qRT-PCR. Results: Rabbits in the Vehicle group showed increased empty bone lacunae, reduced bone trabecula in femoral head; the number of hematopoietic cells in the bone marrow was reduced, whereas number of adipocytes increased with evident fusion phenomenon in comparison with the Control group. All of the changes induced in Vehicle group were attenuated in Ghrelin group. MRI scanning showed obvious necrosis of femoral head in the Vehicle group and less in the Ghrelin group. The mRNA levels of VEGF and BMP-2 were raised in Vehicle group and further enhanced in Ghrelin group. Conclusion: Ghrelin attenuates steroid-induced avascular necrosis in femoral head in rabbit model. A possible mechanism may be through VEGF/BMP-2 axis. Keywords: ANFH, BMP-2, Ghrelin, VEGF

scholarly journals The significance of polymorphisms of gene coagulation factors VII and XIII in the pathogenesis of non-traumatic avascular necrosis of the femoral head

2021 ◽  
Vol 27 (1) ◽  
pp. 43-47
Author(s):  
M.A. Panin ◽  
◽  
N.V Zagorodnii ◽  
A.V. Boiko ◽  
L.M. Samokhodskaya ◽  
...  
Keyword(s):  
Femoral Head ◽  
Avascular Necrosis ◽  
Coagulation Factors ◽  
Group Differences ◽  
Unknown Etiology ◽  
Control Group ◽  
Study Group ◽  
Control Groups ◽  
Aseptic Necrosis ◽  
And Control

Introduction Non-traumatic avascular necrosis of the femoral head (ANFH) is a poly-etiologic and socially significant disease in the age of 20 to 50 years and is associated with disability. Research on the identification of necrosis causes/predictors is a relevant issue. Purpose To study the contribution of polymorphisms in the genes of coagulation factors F7 and F13 in the aetiology of non-traumatic avascular necrosis of the femoral head. Methods Polymorphisms of the genes of coagulation factors F7 and F13 were studied; comparative analysis of the frequency of important allelic variants of F7genes (Arg353Gln) and F13 (Val134Leu) in patients with a verified diagnosis of aseptic necrosis (study group) and in healthy patients (control group) was performed. The study group included 41 patients (all males) with aseptic necrosis of the femoral head of unknown etiology. Results The frequency of gene alleles in the F7 Arg353Gln in the study group were: GG in 30 out of 41 patients (73.2 %), GA in 11 out of 41 patients (26.8 %), and none of 41 patients had a polymorphic variant AA. The frequency of alleles of this type of gene in the control group was as follows: GG in 7 out of 320 subjects (2.2 %), GA in 66 out of 320 patients (20.6 %), AA in 247 out of 320 (77.2 %). Significant differences were identified in the frequencies of homozygous genotypes, AA (χ2 = 100.215, p < 0.001) and GG (χ2 = 205.770, p < 0.001) in the study and control groups respectively. As for the heterozygous GA genotype, the differences were not significant (χ2 = 0.834, p = 0.362). The GG genotype of the gene Val134Leu F13 WAS 2.8 times more frequent in patients of the study group, differences were statistically significant (26.8 % against 9.7 %, χ2 = 10.388; p = 0.002). The presence of the TT genotype of the gene Val134Leu F13 was almost five times more frequent (χ2 = 18.956, p < 0.001) in healthy individuals (control group). Differences in the frequency of allele T in homo/ and heterozygous combinations (TT and GT) in the study and control groups was also significant (72.7 % vs 90.1 %, respectively, χ2 = 4.946, p = 0.027). Discussion Polymorphisms of coagulation factors genes F7 and F13 have a significant effect on the genesis of non-traumatic avascular necrosis of the femoral head. Risk factor of ANFH development is homozygous GG genotype in the gene Arg353Gln F7. Low probability of the disease is due to a protective role of AA genotype of the gene Arg353Gln F7 and TT genotype of the gene Val134Leu F13.

GHSR deficiency exacerbates cardiac fibrosis: role in macrophage inflammasome activation and myofibroblast differentiation

2019 ◽  
Vol 116 (13) ◽  
pp. 2091-2102 ◽  
Author(s):  
Mo Wang ◽  
Lei Qian ◽  
Jing Li ◽  
Hao Ming ◽  
Li Fang ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Cardiovascular Effects ◽  
Transforming Growth Factor Β ◽  
Underlying Mechanism ◽  
Marker Genes ◽  
Inflammasome Activation ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue

Abstract Aims Sustained activation of β-adrenergic signalling induces cardiac fibrosis, which marks progression to heart failure. GHSR (growth hormone secretagogue receptor) is the receptor for ghrelin, which is an orexigenic gastric hormone with newly defined cardiovascular effects. The present study determined the effects of GHSR deficiency in a mouse model of isoproterenol (ISO)-induced cardiac fibrosis and examined the underlying mechanism. Methods and results Histochemical studies showed that GHSR deficiency exacerbated cardiac fibrosis. Quantitative RT–PCR, western blotting, and immunofluorescence staining demonstrated that cardiac fibroblasts isolated from GHSR−/− mice exhibited increased expression of marker genes for myofibroblast trans-differentiation (α-SMA, SM22, and calponin) upon transforming growth factor-β treatment compared to wild-type mice. RNA-sequencing of heart transcriptomes revealed that differentially expressed genes in GHSR−/− hearts were enriched in such biological processes as extracellular matrix organization, inflammatory response, lipid metabolism, cell cycle, migration, and adhesion. Particularly, GHSR deficiency increased Wnt/β-catenin pathway activation in ISO-induced myocardial fibrosis. In addition, loss of GHSR in macrophages instigated inflammasome activation with increased cleavage and release of interleukin-18. Conclusion These results for the first time demonstrated that GHSR deficiency aggravated ISO-induced cardiac fibrosis, suggesting that GHSR was a potential target for the intervention of cardiac fibrosis.

scholarly journals Rabbit Model of Extending Knee Joint Contracture: Progression of Joint Motion Restriction and Subsequent Joint Capsule Changes after Immobilization

2018 ◽  
Vol 33 (01) ◽  
pp. 015-021 ◽  
Author(s):  
Yun Zhou ◽  
Quan Bing Zhang ◽  
Hua Zhang Zhong ◽  
Yi Liu ◽  
Jun Li ◽  
...  
Keyword(s):  
Knee Joint ◽  
Range Of Motion ◽  
Rabbit Model ◽  
Joint Capsule ◽  
Joint Contracture ◽  
Control Group ◽  
Mrna Levels ◽  
Joint Range Of Motion ◽  
Joint Range ◽  
Tgf Β1

AbstractThis study aimed to develop a rabbit model of knee contracture in extension and investigate the natural history of motion loss and time-dependent changes in the joint capsule after immobilization. We immobilized the unilateral knee joints of 32 rabbits by maintaining the knee joint in a plaster cast at full extension. Eight rabbits were euthanized at 2, 4, 6, and 8 weeks after casting, respectively, and the lower extremities were disarticulated at the hip joint. Eight control group rabbits that did not undergo immobilization were also examined. We assessed the progression of joint contracture by measuring the joint range of motion, evaluating the histologic alteration of the capsule, and assessing the mRNA levels of transforming growth factor β1 (TGF-β1) in the anterior and posterior joint capsules. After 2 weeks of joint immobilization, the knee joint range of motion was limited, the synovial membrane of the suprapatellar and posterior joint capsules was thickened, the collagen deposition was increased, and the mRNA levels of TGF-β1 were elevated in the anterior and posterior joint capsules. These changes progressed rapidly until 6 weeks of immobilization and may advance slowly after 6 weeks. Joint contracture developed at the early stage of immobilization and progressed over time. The changes in the anterior and posterior joint capsules after joint immobilization may contribute to the limitation in flexion. The elevated mRNA expression of TGF-β1 may be related to joint capsule fibrosis and may be one of the causes of joint contracture.

scholarly journals Early detection of steroid-induced femoral head necrosis using 99mTc-Cys-Annexin V-based apoptosis imaging in a rabbit model

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Xiaolong Wang ◽  
Jianbo Li ◽  
Da Man ◽  
Rui Liu ◽  
Jianmin Zhao
Keyword(s):  
Femoral Head ◽  
Photon Emission ◽  
Rabbit Model ◽  
Annexin V ◽  
Spect Imaging ◽  
Femoral Head Necrosis ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Control Group ◽  
Emission Computed Tomography ◽  
Target Tissue

Abstract Background At present, the early diagnosis of femoral head necrosis mainly relies on Magnetic resonance imaging (MRI), and most early patients are difficult to make an accurate diagnosis. Therefore, to investigate the early diagnostic value of 99mTc-Cys-Annexin V Single-photon emission computed tomography (SPECT) imaging were compared with MRI in rabbit models of steroid-induced femoral head necrosis. Methods The animal model of steroid-induced femoral head necrosis (SIFHN) was established in 5-month-old healthy New Zealand white rabbits by injecting horse serum into ear vein and methylprednisolone into gluteal muscle, the purpose of modeling is to simulate the actual clinical situation of SIFNH. 99mTc-Cys-Annexin V SPECT imaging and MRI were performed at 2nd week, 4th week, and 6th week after modeling. After that, histopathology was used to verify the success of modeling. Apoptosis was detected by transmission electron microscopy (TEM) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). Results At 2 weeks after the injection of hormone, 99mTc-Cys-Annexin V SPECT image showed abnormal radioactive uptake in the bilateral femoral head. And over time, the radioactivity concentration was more obvious, and the ratio of T/NT (target tissue/non-target tissues, which is the ratio of femoral head and the ipsilateral femoral shaft) was gradually increased. In the 99mTc-Cys-Annexin V SPECT imaging at each time point, T/NT ratio of the model group was significantly higher than that of the control group (P < 0.01); at 4 weeks after the injection of hormone, MRI showed an abnormal signal of osteonecrosis. At 2, 4, and 6 weeks after hormone injection, apoptosis was observed by TUNEL and TEM. Conclusions 99mTc-Cys-Annexin V SPECT imaging can diagnose steroid-induced femoral head necrosis earlier than MRI, and has potential application value for non-invasively detecting early and even ultra-early stage of femoral head necrosis.

scholarly journals Enoxaparin Prevents Steroid-Related Avascular Necrosis of the Femoral Head

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Rainer Beckmann ◽  
Hayfaa Shaheen ◽  
Nisreen Kweider ◽  
Alireza Ghassemi ◽  
Athanassios Fragoulis ◽  
...  
Keyword(s):  
Body Weight ◽  
Femoral Head ◽  
Avascular Necrosis ◽  
Weight Control ◽  
Thrombus Formation ◽  
Control Group ◽  
Significant Difference ◽  
The Usa ◽  
Body Weight Control ◽  
Phosphate Buffered Saline

Nontraumatic osteonecrosis of the femoral head is still a challenging problem in orthopedic surgery. It is responsible for 10% of the 500,000 hip replacement surgeries in the USA and affects relatively young, active patients in particular. Main reasons for nontraumatic osteonecrosis are glucocorticoid use, alcoholism, thrombophilia, and hypofibrinolysis (Glueck et al., 1997; Orth and Anagnostakos, 2013). One pathomechanism of steroid-induced osteonecrosis is thought to be impaired blood flow to the femoral head caused by increased thrombus formation and vasoconstriction. To investigate the preventive effect of enoxaparin on steroid-related osteonecrosis, we used male New Zealand white rabbits. Osteonecrosis was induced by methylprednisolone-injection (1×20 mg/kg body weight). Control animals were treated with phosphate-buffered saline. Treatment consisted of an injection of 11.7 mg/kg body weight of enoxaparin per day (Clexane) in addition to methylprednisolone. Four weeks after methylprednisolone-injection the animals were sacrificed. Histology (hematoxylin-eosin and Ladewig staining) was performed, and empty lacunae and histological signs of osteonecrosis were quantified. Histomorphometry revealed a significant increase in empty lacunae and necrotic changed osteocytes in glucocorticoid-treated animals as compared with the glucocorticoid- and Clexane-treated animals and with the control group. No significant difference was detected between the glucocorticoid and Clexane group and the control group. This finding suggests that cotreatment with enoxaparin has the potential to prevent steroid-associated osteonecrosis.Corrigendum to “Enoxaparin Prevents Steroid-Related Avascular Necrosis of the Femoral Head”

scholarly journals A Rabbit Model of Hormone-induced Early Avascular Necrosis of the Femoral Head

2008 ◽  
Vol 21 (5) ◽  
pp. 398-403 ◽  
Author(s):  
Qian WEN ◽  
Li MA ◽  
Yan-Ping CHEN ◽  
Lin YANG ◽  
Wei LUO ◽  
...  
Keyword(s):  
Femoral Head ◽  
Avascular Necrosis ◽  
Rabbit Model

scholarly journals Gastroprotective and Antioxidative Effects of the Traditional Thai Polyherbal Formula Phy-Blica-D against Ethanol-Induced Gastric Ulcers in Rats

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 172
Author(s):  
Sineenart Sanpinit ◽  
Piriya Chonsut ◽  
Chuchard Punsawad ◽  
Palika Wetchakul
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Underlying Mechanism ◽  
Gastric Ulcers ◽  
Vehicle Group ◽  
Control Group ◽  
Antioxidant Enzyme Activities ◽  
Ulcer Area ◽  
Stress Markers ◽  
Antioxidative Effects

Phy-Blica-D is a traditional Thai polyherbal formula that has reduced oxidative stress in non-communicable diseases. However, evidence supporting the gastroprotective effects of Phy-Blica-D has not been previously reported. Therefore, this study aimed to evaluate the gastroprotective effects of Phy-Blica-D against gastric ulcers in rats and investigate the potential underlying mechanism. To estimate the possible mechanisms of action, we examined the levels of oxidative stress markers, such as reactive oxygen species (ROS) and malondialdehyde (MDA), as well as antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH). According to our results, rats treated with only 80% ethanol (vehicle group) exhibited significant increases in their ulcer area and ulcer index (UI). Moreover, the levels of ROS and MDA markedly increased in the vehicle group compared with the normal control group. Daily oral administration of Phy-Blica-D (500 and 1000 mg/kg) for 7 days not only significantly decreased the ulcer area and UI, but also remarkably decreased the ROS and MDA levels in gastric tissue. Gastric ulcers induced by ethanol had significantly decreased antioxidant enzyme activities (CAT and SOD) and non-enzymatic antioxidant (GSH), whereas pretreatment with Phy-Blica-D significantly improved the activities of CAT, SOD, and GSH. Moreover, after exposure to ethanol, the rats exhibited a significantly increased level of inducible nitric oxide synthase (iNOS), which was reduced after treatment with Phy-Blica-D. These findings suggest that Phy-Blica-D potentially exerts its gastroprotective effects by suppressing oxidative stress and stimulating antioxidant enzymes, which is one of the causes of destruction of cell membranes, and it is involved in the pathogenesis of acute gastric ulcers induced by ethanol.

scholarly journals Early Detection of Steroid-Induced Femoral Head Necrosis using 99mTc-Cys-Annexin V-based Apoptosis Imaging in a Rabbit Model

2020 ◽  
Author(s):  
Xiaolong Wang ◽  
Jianbo Li ◽  
Da Man ◽  
Rui Liu ◽  
Jianmin Zhao
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Femoral Head ◽  
Rabbit Model ◽  
Annexin V ◽  
Spect Imaging ◽  
Femoral Head Necrosis ◽  
Control Group ◽  
Target Tissue ◽  
Transmission Electron

Abstract Background At present, the early diagnosis of femoral head necrosis mainly relies on MRI, and most early patients are difficult to make an accurate diagnosis. Therefore, to investigate the early diagnostic value of 99mTc-Cys-Annexin V SPECT imaging were compared with MRI in rabbit models of steroid-induced femoral head necrosis. Methods The rabbit models of steroid-induced femoral head necrosis were established by intravenous injection of horse serum and gluteal muscle injection of methylprednisolone in of 5-month-old healthy New Zealand white rabbits. 99mTc-Cys-Annexin V SPECT imaging and MRI were performed at 2nd week, 4th week, and 6th week after modeling. After that, histopathology was used to verify the success of modeling. Apoptosis was detected by transmission electron microscopy and TUNEL. Results At 2 weeks after the injection of hormone, 99mTc-Cys-Annexin V SPECT image showed abnormal radioactive uptake in the bilateral femoral head. And over time, the radioactivity concentration was more obvious, and the ratio of T/NT (target tissue/non-target tissues) was gradually increased. In the SPECT imaging at each time point, T/NT ratio of the model group was significantly higher than that of the control group (P < 0.01); at 4 weeks after the injection of hormone, MRI showed an abnormal signal of osteonecrosis. At 2, 4, and 6 weeks after hormone injection, apoptosis was observed by TUNEL and transmission electron microscopy. Conclusions 99mTc-Cys-Annexin V SPECT imaging can diagnose steroid-induced femoral head necrosis earlier than MRI, and has potential application value for non-invasively detecting early and even ultra-early stage of femoral head necrosis.

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