Alendronate Regulates Knee Arthritis by Extracellular-Signal-Regulated Kinase (ERK) Pathway in Rat Model

2021 ◽  
Vol 11 (8) ◽  
pp. 1483-1489
Author(s):  
Xin Jin ◽  
Lu Zi ◽  
Xiaojun Hu
Keyword(s):  
Bone Density ◽  
Rat Model ◽  
Joint Inflammation ◽  
Group Model ◽  
Erk Pathway ◽  
Pathological Changes ◽  
Model Group ◽  
Mankin Score ◽  
Knee Arthritis ◽  
Inflammatory Infiltration

The incidence of knee arthritis is high and treatment effect is not satisfactory. Alendronate (ALN) can treat metabolic bone diseases. But its role and mechanism in knee arthritis remains unclear. SD rats were randomly assigned into control group; model group; and alendronate group followed by analysis of the pathological changes by HE staining and Masson staining, bone mineral density by dual energy bone densitometry, expression of glycosaminoglycan and MMP-3 by immunohistochemistry, BMP-2 and BMP-4 expression by Real time PCR, IL-1β, IL-6 secretion by ELISA as well as ERK signaling protein level by Western blot. In model group, the pathological changes of joint inflammation were obvious with fibrosis on the cartilage surface, significantly increased synovial hyperplasia score, inflammatory infiltration score and Mankin score, decreased bone density, expression of glycosaminoglycan, MMP-3, BMP-2 and BMP-4 as well as increased IL-1β, IL-6 secretion and ERK1/2 expression (P <0.05). Alendronate treatment can significantly improve joint inflammation, reduce inflammatory infiltration score and Mankin score, increase bone density, expression of glycosaminoglycan, MMP-3, BMP-2 and BMP-4, decrease the secretion of IL-1β, IL-6 and expression of ERK1/2 in a rat model of knee arthritis (P <0.05). Alendronate can promote glycosaminoglycans and MMP-3 expression, and synthesis of BMP-2 and BMP-4 by inhibiting ERK pathway, inhibiting the secretion of inflammatory factors, thus ameliorating knee arthritis.

Effect of alendronate sodium on chondrocytes in joint inflammation through down-regulation of microRNA-184 (miR-184)

2021 ◽  
Vol 11 (7) ◽  
pp. 1132-1138
Author(s):  
Lin Shi ◽  
Xiuyun Li ◽  
Junfeng Tang
Keyword(s):  
Western Blot ◽  
Real Time ◽  
Real Time Pcr ◽  
Articular Chondrocytes ◽  
Cell Model ◽  
Joint Inflammation ◽  
Treg Cells ◽  
Inflammatory Factors ◽  
Model Group ◽  
Knee Arthritis

Chondrocytes participate in the progression of osteoarthritis (OA). Alendronate (ALN) can significantly improve the pathological changes of knee arthritis. However, whether alendronate affects chondrocytes of knee arthritis remains unclear. In this paper, the articular chondrocytes were assigned into model group. The inflammation cell model group was prepared using 10 ng/mL IL-1β, the alendronate group was co-cultured with 10 ng/mL IL-1β and 10 ng/mL ALN, and the miR-184 group was transfected with miR-184 siRNA on the basis of an inflammation model followed by the analysis of miR-184, BMP-2 and BMP-4 expression by real-time PCR, IL-1β and IL-22 levels were assayed by means of ELISA, Treg cells were detected by flow cytometry, IL-35 and TGF-β levels were checked by means of real-time PCR and western blot, and Wnt3, Wnt4 and β-Catenin protein levels were investigated by means of western blot. After alendronate and miR-184 siRNA were applied to the arthritis rat model, Treg cells was significantly decreased, IL-35 and TGF-β mRNA and secretion were reduced, miR-184 was down-regulated, BMP-2 and BMP-4 were upregulated, along with decreased IL-1β and IL-22 levels and expressions of Wnt3, Wnt4 and β-Catenin (P < 0.05). Alendronate inhibits Wnt/β-Catenin pathway by down-regulating miR-184, Treg cell and cytokines secretions these cytokines upregulate BMP-2 and BMP-4 in articular chondrocytes, and inhibits inflammatory factors secretion, thus ameliorating the progression of chondrocyte inflammation.

scholarly journals Effect of moxibustion on the expression of GDNF and its receptor GFRα3 in the colon and spinal cord of rats with irritable bowel syndrome

2019 ◽  
Vol 37 (4) ◽  
pp. 244-251 ◽  
Author(s):  
Qin Qi ◽  
Huangan Wu ◽  
Xiaoming Jin ◽  
Duiyin Jin ◽  
Yuanyuan Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Irritable Bowel Syndrome ◽  
Rat Model ◽  
Normal Group ◽  
Mustard Oil ◽  
Group Model ◽  
Model Group ◽  
Moxibustion Group ◽  
Mild Moxibustion ◽  
Irritable Bowel

Background: Moxibustion treatment has been found to ameliorate clinical symptoms including abdominal pain, diarrhoea and constipation in patients with irritable bowel syndrome (IBS). Herein we investigated the mechanisms underlying the use of moxibustion in a rat model of IBS. Methods: In our study, an IBS model was established in rats by colorectal distension (CRD) stimulus and mustard oil enema. The rats were randomly divided into a normal group, model group, mild moxibustion group, electroacupuncture group, probiotic group and dicetel group. Abdominal withdrawal reflex (AWR) scores were determined within 90 min of the last treatment. The expression of GDNF/GFRα3 protein and mRNA in the colon and spinal cord were detected by immunohistochemistry and quantitative real-time-PCR, respectively. Results: The IBS model rats had significantly higher AWR scores than the normal group ( P<0.01). After mild moxibustion treatment, the AWR score was significantly reduced (20 mm Hg, P<0.05; 40 mm Hg, 60 mm Hg and 80 mm Hg, P<0.01). The model group showed significantly more colonic glial cell line-derived neurotrophic factor (GDNF/GFRα3 (GDNF family receptor α3) protein and mRNA expression in the colon and spinal cord than the normal group ( P<0.01). Compared with the model group, the expression of GDNF/GFRα3 protein and mRNA in the colon and spinal cord of the rats were significantly decreased in the mild moxibustion group (colon: GDNF and GFRα3 protein, P<0.01; GDNF and GFRα3 mRNA, P<0.01; spinal cord: GDNF and GFRα3 protein, P<0.01; GDNF mRNA, P<0.05, GFRα3 mRNA, P<0.01). Conclusions: Our data suggest that moxibustion therapy may mitigate CRD-induced increases in the expression of GDNF and its receptor GFRα3 in the colon and spinal cord in a rat model of IBS.

scholarly journals Sinomenine Hydrochloride Attenuates Renal Fibrosis by Inhibiting Excessive Autophagy Induced by Adriamycin: An Experimental Study

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Ming-ming Zhao ◽  
Bin Yang ◽  
Qiu Zhang ◽  
Jin-hu Wang ◽  
Jin-ning Zhao ◽  
...  
Keyword(s):  
Rat Model ◽  
Renal Fibrosis ◽  
Beclin 1 ◽  
Control Group ◽  
Intragastric Administration ◽  
Group Model ◽  
Pathological Changes ◽  
Sprague Dawley ◽  
H Protein ◽  
Sinomenine Hydrochloride

The objective of this study is to investigate if sinomenine hydrochloride (SIN-HCl) could be effective against adriamycin-induced renal fibrosis by regulating autophagy in a rat model. Forty male Sprague-Dawley (SD) rats were randomly divided into control group, model group, telmisartan group, and SIN-HCl group; rat model was induced by adriamycin; all rats were given intragastric administration for 6 weeks. Urine was collected from rats in metabolic cages to determine 24 h protein level. This was done after intragastric administration for the first two weeks and then once for every two weeks. Renal pathological changes were examined by the staining of HE, Masson, and PASM. Expressions and distributions of fibronectin (FN), laminin (LN), light chain 3 (LC3), and Beclin-1 were observed by immunohistochemistry. SIN-HCl ameliorates proteinuria, meanwhile attenuating the renal pathological changes in adriamycin-induced rats and also attenuating renal fibrosis and excessive autophagy by reducing the expression of FN, LN, LC3, and Beclin-1. SIN-HCl attenuates renal fibrosis by inhibiting excessive autophagy induced by adriamycin and upregulates the basal autophagy.

scholarly journals Effect of Heweianshen Decoction on Orexin-A and Cholecystokinin-8 Expression in Rat Models of Insomnia

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Fagen Li ◽  
Shaodan Li ◽  
Yi Liu ◽  
Ke Cao ◽  
Minghui Yang
Keyword(s):  
Rat Model ◽  
Wistar Rats ◽  
High Dose ◽  
Intragastric Administration ◽  
Group Model ◽  
Model Group ◽  
Orexin A ◽  
Blank Group ◽  
Rat Models ◽  
Male Wistar Rats

Objective. To study the effect of Heweianshen decoction (HAD) on orexin-A and cholecystokinin-8 (CCK-8) expression in rat models of insomnia caused by injecting parachlorophenylalanine (PCPA) intraperitoneally.Methods. Fifty male Wistar rats were randomly divided into five groups (10 rats in each group): blank group, model group, and low-, medium-, and high-dose HAD-treated groups. A rat model of insomnia was established by injecting intraperitoneally with PCPA (300 mg/kg body weight). Rats were given normal saline (10 mL/kg) or 5.25, 10.5, and 21 g/kg HAD by intragastric administration once a day for 6 days. After that, the rats were sacrificed to collect the hypothalamus for tests, using radioimmunoassay to detect the expression of orexin-A and CCK-8.Results. Heweianshen decoction reduced the expression of orexin-A and increased the expression of CCK-8 in the hypothalamus of rat model of insomnia.Conclusion. The therapeutic effect of HAD on insomnia is partially attributed to the decreased expression of orexin-A and increased expression of CCK-8.

Effect of Nerve Training Technology on Apoptosis of Cartilage and Osteoblasts and Expression of Aggrecan Protein in Osteoporotic Arthritis

2022 ◽  
Vol 12 (1) ◽  
pp. 167-173
Author(s):  
Wei Liu ◽  
Lili Huang ◽  
Cuiying Zhang ◽  
Zuozhong Liu
Keyword(s):  
Flow Cytometry ◽  
Treatment Group ◽  
Group Model ◽  
The Novel ◽  
Model Group ◽  
Mankin Score ◽  
Novel Technique ◽  
Limited Efficacy ◽  
The World ◽  
Mrna And Protein Expression

Arthritis and osteoporosis are two common disorders in the world, especially for the elder, but the current treatments have limited efficacy. Herein, we aimed to determine whether the novel technique, neurological training can alleviate osteoporosis complicated with arthritis in rat model. Thirty rats were assigned into normal group, model group, and treatment group (treated with forsythin and neurological training) (n = 10) followed by assessment of chondrocytes and osteoblasts using Mankin score, apoptosis by TUNEL and flow cytometry, and IL-1β, TNF-α, and Aggrecan levels. Apoptotic chondrocytes of treatment group (27.43±1.34) was lower than model group (p < 0.05), whereas amount of osteoblast was increased upon forsythin and neurological training, with lower Mankin’s score (6.38±0.76). Besides, the content of IL-1β and TNF-α of treatment group was significantly lower but Aggrecan mRNA and protein expression was significantly higher. In conclusion, neurological training could protect and alleviate osteoporosis complicated with arthritis.

An Experimental Study on the Mechanisms of Ge Hua Jie Cheng Decoction for Rats with Alcoholic Liver Injuries

2015 ◽  
Vol 3 (1) ◽  
pp. 60-64
Author(s):  
Zhou-An Yin ◽  
Ya-Nan Mao ◽  
Yuan-Yuan He ◽  
Ling Long ◽  
Cheng-Yu Luo ◽  
...  
Keyword(s):  
White Wine ◽  
Normal Group ◽  
Glutamyl Endopeptidase ◽  
Group Model ◽  
Model Group ◽  
Inflammatory Infiltration ◽  
Liver Injuries ◽  
Biochemical Analyzer ◽  
High Concentrations ◽  
Underlying Mechanisms

Abstract Objective: To explore the effects and underlying mechanisms of Ge Hua Jie Cheng Decoction on rats with alcoholic liver injuries. Methods: 60 Wistar rats were randomly assigned to six groups: normal group, model group, Yi Gan Ling group, and Ge Hua Jie Cheng Decoction groups in low, middle and high concentrations, 10 rats in each group. Except for the normal group, rats in other groups were administered white wine for eight weeks to establish the liver injury model. During the modeling, the Yi Gan Ling/Ge Hua Jie Cheng Decoction were administered intragastrically to the rats. So the histopathological changes were observed after eight weeks, meanwhile the serum γ- glutamyl endopeptidase (GGT), Glutathione (GSH) and aspartate aminotransferase mitochondrial isoenzyme (m-AST) were assayed by automatic biochemical analyzer. Results: under the light microscope, the groups of high and middle dosages of Ge Hua Jie Cheng Decoction , especially the high one, had apparent improvement of inflammatory infiltration in liver tissues. Compared with the normal group, the serum GGT and m-AST levels had elevated (P＜0.01), whereas the serum GSH level decreased (P＜0.01); compared with model group, the high and middle dosages of Ge Hua Jie Cheng Decoction groups had decreased serum GGT and m-AST (P＜0.01 or P＜0.05), as well as increased serum GSH level (P＜0.01). Conclusion: Ge Hua Jie Cheng Decoction has a protective effect for liver injuries induced by alcohol, and this effect is dose-dependent. The high dosage showed stronger protection effect, which might be related to the increased serum GSH and decreased serum GGT and m-AST.

scholarly journals The Anti-Inflammatory Effects of a Yin Zhi Huang Soup in an Experimental Autoimmune Prostatitis Rat Model

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Longsheng Deng ◽  
Xikui Zhang ◽  
Weikun Zhu ◽  
Taikun Lu ◽  
Jinchun Chen ◽  
...  
Keyword(s):  
Body Weight ◽  
Blood Serum ◽  
Rat Model ◽  
Prostate Tissue ◽  
Therapeutic Effects ◽  
Pathological Changes ◽  
Model Group ◽  
Necrosis Factor Alpha ◽  
Wet Weight ◽  
Experimental Autoimmune

The present study aimed to investigate the therapeutic effects of the Chinese herbal medicine Yin Zhi Huang soup (YZS) in an experimental autoimmune prostatitis (EAP) rat model. In total, 48 rats were randomly divided into the following four groups (n=12/group): saline group, pathological model group, Qianlietai group, and YZS group. We determined the average wet weight of the prostate tissue, the ratio of the wet weight of the prostate tissue to body weight, tumor necrosis factor-alpha (TNF-α) levels in the blood serum, the expression of inducible nitric oxide synthase (iNOS) in the rats’ prostate tissues, and the pathological changes in the prostate tissue using light microscopy. YZS reduced the rats’ prostate wet weight, the ratio of the prostate wet weight to body weight, and TNF-α levels in the blood serum and inhibited the expression of iNOS in the rats’ prostate tissues (P<0.05). Following YZS treatment, the pathological changes in the rats’ prostates were improved compared with those in the model group (P<0.05). Furthermore, YZS treatment reduced inflammatory changes in the prostate tissue. It also significantly suppressed proinflammatory cytokines, such as TNF-α, and chemokines, such as iNOS, in the rat model of EAP.

scholarly journals Study of the Treatment Effects of Compound Tufuling Granules in Hyperuricemic Rats Using Serum Metabolomics

2018 ◽  
Vol 2018 ◽  
pp. 1-13
Author(s):  
Peng Wu ◽  
Jing Li ◽  
Xianxian Zhang ◽  
Fuling Zeng ◽  
Yingwan Liu ◽  
...  
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Rat Model ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Inflammatory Factors ◽  
Metabolic Profiles ◽  
Group Model ◽  
Model Group

The study aimed to investigate the mechanism of the effect of Compound Tufuling Granules (CTG) to lower the serum uric acid level in a rat model of hyperuricemia. The rat model was established by administering hypoxanthine through oral gavage and potassium oxonate through intraperitoneal injection. Rats were divided into the normal group, model group, CTG group, and allopurinol group. Serum uric acid, creatinine, urea nitrogen, and inflammatory cytokine levels were determined in each group. In the model group, ultrahigh performance liquid chromatography-mass spectrometry was used to analyze the metabolic profiles and delineate the action mechanism of CTG; in addition, the orthogonal projection method was used to perform latent structure-discrimination analysis to screen the related metabolites. The results indicated significant differences in the metabolic profiles between the model and normal groups. A total of seven related metabolites were identified through screening in the model group, mainly related to the pathways of bile secretion, pyrimidine, purine, and phenylalanine metabolism, pantothenate and CoA biosynthesis, and pentose and glucuronate interconversions; these related pathways were reversed in the CTG group. In the metabolic networks, uracil and acetyl-coenzyme A were the nodal molecules. In addition, the test results of the evaluation of serum biochemical and inflammatory factors confirmed that CTG had significant effect in reducing the levels of serum uric acid and protecting renal function. These results confirmed that CTG primarily regulated the recruitment of nodal molecules to achieve anti-inflammatory effects, reduced uric acid level, and renal protection.

Effects of Artesunate on the Expressions of Insulin-Like Growth Factor-1, Osteopontin and C-Telopeptides of Type II Collagen in a Rat Model of Osteoarthritis

Pharmacology ◽  
2017 ◽  
Vol 101 (1-2) ◽  
pp. 1-8 ◽  
Author(s):  
Zhe Bai ◽  
Xiao-Hui Guo ◽  
Chi Tang ◽  
Si-Tong Yue ◽  
Long Shi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Type Ii Collagen ◽  
Cartilage Tissue ◽  
Enzyme Linked Immunosorbent Assay ◽  
Insulin Like Growth Factor ◽  
Type Ii ◽  
Pathological Changes ◽  
Model Group ◽  
Mankin Score ◽  
And Cartilage

Objective: The study aims to explore the effects of artesunate on insulin-like growth factor-1 (IGF-1), Osteopontin (OPN), and C-telopeptides of type II collagen (CTX-II) in serum, synovial fluid (SF), and cartilage tissues of rats with osteoarthritis (OA). Methods: OA models were established. Normal model, artesunate, and Viatril-S groups (20 rats respectively) were set. Enzyme-linked immunosorbent assay, IHC staining, and quantitative real-time polymerase chain reaction were conducted to calculate IGF-1, OPN, and CTX-II levels in serum, SF, and cartilage tissues of rats. The pathological changes in cartilage tissues were evaluated with Mankin score and Hematoxylin-Eosin staining. Results: Compared with the normal group, the model group showed increased IGF-1 level; decreased OPN, CTX-II levels in the serum and SF; and contrary results were seen in the cartilage tissues. A gradual ascending IGF-1 level and descending OPN and CTX-II levels existed in the serum and SF in the artesunate and Viatril-S groups after 2 weeks. The model group showed the most obvious pathological changes and highest Mankin score compared with the other groups. Higher IGF-1 level and lower OPN, CTX-II levels were exhibited in the cartilage tissue in the artesunate and Viatril-S groups but not in the model group. Conclusion: Artesunate and Viatril-S inhibit OA development by elevating IGF-1 level and reducing OPN and CTX-II levels.

scholarly journals Exploring the Mechanism of Berberine Intervention in Ulcerative Colitis from the Perspective of Inflammation and Immunity Based on Systemic Pharmacology

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yan Jiang ◽  
Li Zhao ◽  
Qing Chen ◽  
Lihong Zhou
Keyword(s):  
Ulcerative Colitis ◽  
Protein Expression ◽  
Enrichment Analysis ◽  
The Body ◽  
Signal Pathways ◽  
Group Model ◽  
Pathological Changes ◽  
Model Group ◽  
Colon Tissue ◽  
Tnf Α

Background. Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease of the colon and rectum. Recent studies found that berberine had effects on inflammatory diseases and immune diseases. Methods. The PharmMapper database was used to predict the berberine potential target and GeneCards database and OMIM database were utilized to collect UC genes. The Cytoscape software was used to construct and analyze the networks and DAVID was utilized to perform enrichment analysis. Then, animal experiments were performed to validate the prediction results. The experimental rats were randomly divided into normal group (control group), model group, and berberine group. The general condition, body weight, gross morphology of colon tissue, and colonic mucosal damage index (CMDI) score were observed. The pathological changes of colon tissue were observed by H&E staining. The levels of serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-4 were detected by ELISA. The expressions of IL-1β, TNF-α, and IL-4 protein in colon tissue were detected by immunohistochemistry. Results. A total of 211 Berberine’s potential targets and 210 UC genes were obtained. The enrichment analysis showed that berberine may regulate inflammation, inflammatory cytokines, and their mediated inflammation signal pathways such as inflammatory bowel disease (IBD), rheumatoid arthritis, cytokine-cytokine receptor interaction, TNF, T cell receptor, Toll-like receptor, and JAK/STAT signaling pathway. Compared with the model group, the body mass of rats in the berberine group was significantly increased ( P  < 0.05); the general morphology and pathological changes of colon tissue were significantly improved; CMDI score, serum and colon tissue IL-1β, TNF-α content, and protein expression were decreased significantly ( P  < 0.05); and IL-4 content and protein expression increased significantly ( P  < 0.05). Conclusion. Berberine can interfere with UC through related biological processes and signal pathways related to inflammation and immunity. In-depth exploration of the mechanism of berberine in the treatment of UC will provide a basis for clinical application.

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