scholarly journals Protective Effect of Adalimumab on Diabetic Nephropathy by Regulating TNF-α Signal Pathway

2021 ◽  
Author(s):  
Zhiying Ding ◽  
Hongxia Jiang ◽  
Yongsong Fan ◽  
Guiqin Sun
Keyword(s):  
Animal Model ◽  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Protective Effect ◽  
Weight Ratio ◽  
Inhibitory Effect ◽  
Urinary Albumin ◽  
Sprague Dawley ◽  
Tnf Α ◽  
Model Animal

Background: To evaluate the inhibitory effect of adalimumab on diabetic nephropathyDN) through animal models. Methods: We carried out the study in Weifang People’s Hospital, Weifang 261041, China in December 2020. Streptozotocin was used to induce DN in model animal Sprague-Dawley (SD) rats. The DN animal model was given treatment with adalimumab, and the inhibitory effect of adalimumab on the development process of DN was evaluated by detecting changes in blood glucose and urinary albumin levels. Meanwhile, the content of UN, Cr and CysC of the blood in different experimental groups was tested by weighing the ratio of kidney and performing ELISA to evaluate the protective effect of adalimumab on kidney of DN animal model. In addition, the changes in the transcription and translation levels of tumor necrosis factor α (TNF-α) and its downstream regulatory factors MCP-1 and NF-kB in kidney of different experimental groups were detected by fluorescence quantitative PCR and Western blot tests to further reveal the molecular mechanism of adalimumab inhibiting the diabetic nephropathy. Results: adalimumab could significantly downregulate blood glucose and urinary albumin levels (P <0.05). The renal body weight ratio and the contents of UN, Cr and Cysc in blood in the adalimumab group were significantly lower than those in the placebo group (P <0.05). Meanwhile, adalimumab could significantly downregulate the expression of these molecules (P <0.05). Conclusion: adalimumab could exert its therapeutic effect on diabetic nephropathy through its specific targeting TNF-α signaling pathways.

scholarly journals The expression of POMC and AgRP in brain and kidney tissues at different stages of diabetic nephropathy rats

2021 ◽  
Vol 1 (1) ◽  
pp. 43-49
Author(s):  
Shasha Liu ◽  
Jingjing Da ◽  
Jiayu Li ◽  
Rong Dong ◽  
Jing Yuan ◽  
...  
Keyword(s):  
Body Weight ◽  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Urinary Albumin Excretion ◽  
Excretion Rate ◽  
Kidney Tissue ◽  
Albumin Excretion Rate ◽  
Urinary Albumin ◽  
Urinary Albumin Excretion Rate ◽  
Albumin Excretion

Abstract Objective To explore the changes of proopiomelanocortin (POMC) and Agouti-Related Peptide (AgRP) expression in brain and kidney tissues under insulin intervention at different stages of diabetic nephropathy (DN) rats. Methods The male Sprague-Dawley (SD) rats of DN were treated with high-fat diet for 8 weeks and induced by intraperitoneally injection of streptozotocin (30 mg/kg) for one time. Then DN rats were also injected insulin subcutaneously at 2–5 U/(kg·24 h) from initiation of the streptozotocin. Kidney tissue, blood sample, and 24 h-urine were collected to detect the ratio of kidney/body weight, blood glucose and 24-h urinary albumin excretion rate at different stages (4, 8, 12, and 16 weeks). Immunohistochemistry assay was used to measure the expression of POMC and AgRP at different stages of DN rats. Results The DN rats were established successfully. With the progression of DN, blood glucose, 24-h urinary albumin excretion rate and kidney body weight ratio increased significantly, while decreased when insulin was injected. Immunohistochemistry showed that the expression levels of POMC were decreased gradually in brain and kidney tissues. Conversely, the expression of AgRP in kidney was highest at week 8 and then decreased gradually. The effect of insulin on normalizing POMC and AgRP expression in brain and renal tissues was also observed in DKD rats. Conclusion With the progression of DN, the expression of POMC and AgRP in kidney tissues was observed at different stages of disease, and their expressions were significantly normalized by insulin. The mechanism of in situ expression of POMC and AGRP in kidney to the progression of DN needs further investigations.

scholarly journals Umbelliferone alleviates hepatic injury in diabetic db/db mice via inhibiting inflammatory response and activating Nrf2-mediated antioxidant

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Jiangning Yin ◽  
Hanqing Wang ◽  
Guoyuan Lu
Keyword(s):  
Blood Glucose ◽  
Inflammatory Response ◽  
Protective Effect ◽  
High Mobility ◽  
Hepatic Function ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Stress Indicators ◽  
Tnf Α ◽  
Oxidative Stress Indicators

The current study was designed to investigate the protective effect and possible mechanisms of umbelliferone (Umb) on liver injury in diabetic C57BL/KsJ-db/db (dbdb) mice. Mice were divided into five groups: wild-type mice group (WY), dbdb mice group, dbdb mice + Metformin (100 mg/kg) group, dbdb mice + Umb (20, 40 mg/kg) group. Blood glucose regulation was assessed by an oral glucose tolerance test (OGTT). At 28 days after drug administration, blood samples were obtained for the analysis of lipids and enzymes related to hepatic function, including alanine aminotransferase (ALT), aspartate aminotransaminase (AST) and total cholesterol (TC) and triglyceride (TG). Expression levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and oxidative stress indicators (SOD and MDA) were measured with ELISA kit. The expressions of high-mobility group box 1 (HMGB1), Toll-like receptor (TLR) 4 (TLR4), Myd88, NF-κB, IκB, Nrf2, and HO-1 proteins were also evaluated by Western blotting analysis. The results showed that Umb significantly restored the blood glucose in OGTT, and inhibited the levels of insulin, TG, TC, as well as activities of ALT and AST. Moreover, Umb inhibited diabetic inflammation through down-regulating the expression of HMGB1, TLR4, NF-κB, and IκB. In addition, Umb alleviated oxidative damage in the liver by activating Nrf2-mediated signal pathway. These findings demonstrated that Umb exhibited protective effect against diabetic live injury, which may be through inhibiting HMGB1-induced inflammatory response and activating Nrf2-mediated antioxidant.

scholarly journals Synergistic reduction in albuminuria in type 2 diabetic mice by esaxerenone (CS-3150), a novel nonsteroidal selective mineralocorticoid receptor blocker, combined with an angiotensin II receptor blocker

2020 ◽  
Vol 43 (11) ◽  
pp. 1204-1213
Author(s):  
Kiyoshi Arai ◽  
Yuka Morikawa ◽  
Naoko Ubukata ◽  
Kotaro Sugimoto
Keyword(s):  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Mineralocorticoid Receptor ◽  
Antihypertensive Effect ◽  
Urinary Albumin ◽  
Receptor Blocker ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor ◽  
Ay Mice

AbstractEsaxerenone is a novel selective mineralocorticoid receptor (MR) blocker that was recently approved in Japan to treat hypertension. In phase II and III studies, esaxerenone plus a renin–angiotensin system inhibitor markedly reduced the urinary albumin-to-creatinine ratio (UACR) in hypertensive patients with diabetic nephropathy. To evaluate a direct renoprotective effect by MR blockade independent of an antihypertensive effect in the context of diabetic nephropathy, esaxerenone (3 mg/kg), olmesartan (an angiotensin II receptor blocker; 1 mg/kg), or both were orally administered to KK-Ay mice, a type 2 diabetes model, once daily for 56 days. Urinary albumin (Ualb), UACR, and markers, such as podocalyxin, monocyte chemoattractant protein-1 (MCP-1), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), were measured, along with systolic blood pressure (SBP), fasting blood glucose, and serum K+ levels. Prior to the initiation of drug administration, KK-Ay mice showed higher blood glucose, insulin, Ualb excretion, and UACR levels than C57BL/6 J mice, a nondiabetic control, indicating the development of diabetic renal injury. Combined treatment with esaxerenone and olmesartan significantly reduced the change in UACR from baseline compared with the change associated with vehicle at week 8 (−1.750 vs. 0.339 g/gCre; P < 0.002) and significantly inhibited the change in Ualb from baseline compared with the change associated with vehicle at week 8 (P < 0.002). The combination treatment also reduced urinary excretion of podocalyxin and MCP-1, but did not influence 8-OHdG excretion, SBP, blood glucose, or serum K+ levels. Overall, esaxerenone plus olmesartan treatment ameliorated diabetic nephropathy in KK-Ay mice without affecting SBP, suggesting that the renoprotective effects of esaxerenone could be exerted independently of its antihypertensive effect.

scholarly journals Protective effect of Cordyceps sinensis extract on lipopolysaccharide-induced acute lung injury in mice

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Shuiqiao Fu ◽  
Weina Lu ◽  
Wenqiao Yu ◽  
Jun Hu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Weight Ratio ◽  
Cordyceps Sinensis ◽  
Myeloperoxidase Activity ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Tnf Α ◽  
Cox 2

Abstract Background: To study the protective effect of Cordyceps sinensis extract (Dong Chong Xia Cao in Chinese [DCXC]) on experimental acute lung injury (ALI) mice. Methods and results: ALI model was induced by intratracheal-instilled lipopolysaccharide (LPS, 2.4 mg/kg) in BALB/c male mice. The mice were administrated DCXC (ig, 10, 30, 60 mg/kg) in 4 and 8 h after receiving LPS. Histopathological section, wet/dry lung weight ratio and myeloperoxidase activity were detected. Bronchoalveolar lavage fluid (BALF) was collected for cell count, the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and nitric oxide (NO) in BALF was detected by ELISA, the protein and mRNA expression of nuclear factor-κB p65 (NF-κB p65), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung tissue was detected by Western blot and RT-PCR. The result showed that DCXC could reduce the degree of histopathological injury, wet/dry weight ratio (W/D ratio) and myeloperoxidase activity (P<0.05) with a dose-dependent manner. The increased number of total cells, neutrophils and macrophages in BALF were significantly inhibited by DCXC treatment (P<0.05). The increased levels of TNF-α, IL-1β, IL-6 and NO in BALF after LPS administration was significantly reduced by DCXC (P<0.05). In addition, the increased protein and mRNA levels of iNOS, COX-2 and NF-κB p65 DNA binding ability in LPS group were dose-dependently reduced by DCXC treatment (P<0.05). Conclusion: DCXC could play an anti-inflammatory and antioxidant effect on LPS-induced ALI through inhibiting NF-κB p65 phosphorylation, and the expression of COX-2 and iNOS in lung. The result showed that DCXC has a potential protective effect on the ALI.

scholarly journals miR-92d-3p suppresses the progression of diabetic nephropathy renal fibrosis by inhibiting the C3/HMGB1/TGF-β1 pathway

2021 ◽  
Author(s):  
Yuhua Zhang
Keyword(s):  
Animal Model ◽  
Diabetic Nephropathy ◽  
Renal Fibrosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Factor ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Tnf Α ◽  
Tgf Β1 ◽  
E Cadherin

The pathogenesis of diabetic nephropathy (DN) has not been fully elucidated. MicroRNAs play an important role in the onset and development of DN renal fibrosis. Thus, this study aimed to investigate the effect of miR-92d-3p on the progression of DN renal fibrosis. We used qRT-PCR to detect the expression levels of miR-92d-3p in the kidneys of patients with DN. Then, after transfecting lentiviruses containing miR-92d-3p into the kidneys of a DN mouse model and HK-2 cell line, we used qRT-PCR to detect the expression levels of miR-92d-3p, C3, HMGB1, TGF-β1, α-SMA, E-cadherin, and Col Ⅰ. The expression levels of IL-1β, IL-6, and TNF-α in the HK-2 cells were detected through enzyme-linked immunosorbent assay, and Western blotting and immunofluorescence were used in detecting the expression levels of fibronectin, α-SMA, E-cadherin, and vimentin. Results showed that the expression levels of miR-92d-3p in the kidney tissues of patients with DN and DN animal model mice decreased, and C3 stimulated HK-2 cells to produce inflammatory cytokines. The C3/HMGB1/TGF-β1 pathway was activated, and EMT was induced in the HK-2 cells after human recombinant C3 and TGF-β1 protein were added. miR-92d-3p inhibited inflammatory factor production by C3 in the HK-2 cells and the activation of the C3/HMGB1/TGF-β1 pathway and EMT by C3 and TGF-β1. miR-92d-3p suppressed the progression of DN renal fibrosis by inhibiting the activation of the C3/HMGB1/TGF-β1 pathway and EMT.

scholarly journals Protective effect of syringaresinol on rats with diabetic nephropathy via regulation of Nrf2/HO-1 and TGF- β1/Smads pathways

2022 ◽  
Vol 20 (2) ◽  
pp. 275-280
Author(s):  
Lei Ji ◽  
Xue Zhong ◽  
Xingxing Xia ◽  
Wei Yu ◽  
Yuping Qin
Keyword(s):  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Protective Effect ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Pathological Changes ◽  
Tgf Β1

Purpose: To investigate the protective role of syringaresinol in a rat model of diabetic nephropathy (DN). Methods: Streptozotocin was injected intraperitoneally into rats to establish the diabetic model. Streptozotocin-induced rats were orally administered syringaresinol, and pathological changes in kidneys were assessed using hematoxylin and eosin staining. Enzyme-linked immunosorbent assay (ELISA) was used to determine kidney injury indicators, 24-h urine proteins, blood urea nitrogen (BUN), and serum creatinine (SCR). Blood glucose was measured using a blood glucose meter, while levels of malonaldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) in kidney were also measured using ELISA. Results: Pathological changes in the kidneys were observed in rats post-streptozotocin treatment. Administration of syringaresinol reduced the lesion degree, with improved pathological morphology in kidney. Syringaresinol administration significantly attenuated streptozotocin-increased levels of BUN, SCR, 24-h urine protein, and blood glucose (p < 0.01). Streptozotocin-induced oxidative stress, shown by enhanced MDA level and reduced levels of SOD, CAT, and GSH-PX, was reversed in rat kidneys following syringaresinol administration. However, the expression levels of nuclear factor erythropoietin- 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) proteins decreased, while transforming growth factor-beta 1 (TGF-β1) and signal transducer and transcriptional modulator (Smad) 2/3/7 proteins increased in rats post-streptozotocin treatment. Syringaresinol administration reversed the effects of streptozotocin on protein expression of Nrf2, HO-1, TGF-β1, and Smad 2/3/7. Conclusion: Syringaresinol exerted a protective effect against DN through activation of Nrf2 and inactivation of TGF-β1/Smad pathways. Thus, the compound can potentially be developed for management of diabetic nephropathy.

scholarly journals Temporal modulation of host aerobic glycolysis determines the outcome of M. marinum infection

2018 ◽  
Author(s):  
Lu Meng ◽  
Lingling Xie ◽  
Yuanqing Kan ◽  
Lixia Liu ◽  
Wenyue Dong ◽  
...  
Keyword(s):  
Protective Effect ◽  
Host Defense ◽  
Aerobic Glycolysis ◽  
Intervention Strategy ◽  
Mycobacterial Infection ◽  
Inhibitory Effect ◽  
Infection Model ◽  
Necrosis Factor Alpha ◽  
Tnf Α

Macrophages are the first-line host defense where the invading Mycobacterium tuberculosis (Mtb) encounters. It has been recently reported that host aerobic glycolysis was elevated post the infection by a couple of virulent mycobacterial species. However, whether this metabolic transition is required for host defense against intracellular pathogens and the underlying mechanisms remain to be further investigated. By analyzing carbon metabolism, we found that macrophages infected by M. marinum, a surrogate mycobacterial specie to Mtb, showed a strong elevation of glycolysis. Next, three glycolysis inhibitors were examined for their ability to inhibit mycobacterial proliferation inside RAW264.7, a murine macrophage-like cell line. Among them, a glucose analog, 2-deoxyglucose (2-DG) displayed a protective effect on assisting host to resist mycobacterial infection, which was further validated in zebrafish-infection model. The phagocytosis of M. marinum was significantly decreased in macrophages pre-treated with 2-DG at concentrations of 0.5 and 1 mM, at which no inhibitory effect was posed on M. marinum growth in vitro. Moreover, 2-DG pre-treatment exerted a significant protective effect on zebrafish larvae to limit the proliferation of M. marinum, and such effect was correlated to tumor necrosis factor alpha (TNF-α). On the contrary, the 2-DG treatment post infection did not restrain proliferation of M. marinum in WT zebrafish, and even accelerated bacterial replication in TNF-α-/- zebrafish. Together, modulation of glycolysis prior to infection boosts host immunity against M. marinum infection, indicating a potential intervention strategy to control mycobacterial infection.

The Protective Effect of Notoginsenoside R1 on Isoflurane-Induced Neurological Impairment in the Rats via Regulating miR-29a Expression and Neuroinflammation

2021 ◽  
pp. 1-7
Author(s):  
Meijing Wang ◽  
Hongyan Liu ◽  
Lufeng Xu ◽  
Mengmeng Li ◽  
Ming Zhao
Keyword(s):  
Protective Effect ◽  
Neuroprotective Effect ◽  
Neurological Impairment ◽  
Morris Water Maze Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Spatial Learning And Memory ◽  
Sprague Dawley ◽  
Real Time Quantitative Pcr ◽  
Rat Pups ◽  
Tnf Α

<b><i>Introduction:</i></b> Isoflurane inhalation leads to apoptotic neurodegeneration and further results in learning and cognitive dysfunction. Notoginsenoside R1 (NGR1), a major ingredient from Radix notoginseng, has been reported to exert neuroprotective effect during brain or neuron injury. This study aimed to investigate the effect of NGR1 on neurological impairment. <b><i>Methods:</i></b> Sixty-four male Sprague Dawley rat pups (15–20 g) of postnatal day 7 were recruited. Spatial learning and memory were assessed by the Morris water maze test, and the neurological severity score was determined. Real-time quantitative PCR was used to detect the expression levels of microRNA (miR)-29a. Enzyme-linked immunosorbent assay was applied to estimate the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the hippocampal tissues. <b><i>Results:</i></b> NGR1 attenuated neurological impairment induced by isoflurane, shown by the decrease in neurological function score and escape latency and the increase in staying time in the original quadrant in rats. NGR1 reversed the downregulation of miR-29a expression induced by isoflurane treatment. After the treatment of NGR1, the elevated levels of IL-6, TNF-α, and IL-1β induced by isoflurane were all decreased significantly in the hippocampal tissues of rats. Additionally, the repressive action of NGR1 in neurological impairment and neuroinflammation was eliminated by downregulating miR-29a in rats. <b><i>Conclusion:</i></b> NGR1 protects against isoflurane-induced neurological impairment. The protective effect of NGR1 might be achieved by promoting the expression of miR-29a and preventing inflammatory response.

scholarly journals Effect of Repaglinide on Blood Glucose, Endothelial Function, Lipid Metabolism, and Inflammatory Reaction in a Rat Model of Atherosclerosis

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582091876
Author(s):  
Jie Chang ◽  
Bing Liu ◽  
Yan-xia Cheng ◽  
Jin-guang Zhang ◽  
Shuo Tao ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Protective Effect ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherogenic Index ◽  
Control Group ◽  
Model Group ◽  
Sprague Dawley ◽  
Plasminogen Activator Inhibitor 1 ◽  
Epididymal Fat

Objective: To investigate the protective effect of repaglinide on rat with atherosclerosis. Methods: Sprague Dawley (SD) rats were divided into control, model, repaglinide, and metformin groups. In addition to the normal group, rats were given intraperitoneal injection of streptozotocin and high-fat diet (HFD). Meanwhile, repaglinide or metformin was administrated to the treatment rats, respectively, for 4 weeks. Serum, plasma, liver, epididymal fat, and aorta thoracica were obtained to observe the protective effect of repaglinide on rat with atherosclerosis. Results: Compared to the control group, blood glucose was increased in the model group ( P < .05), while it was decreased in the drug-administered groups. In addition, the levels of endothelin 1, TG, TC, low-density lipoprotein cholesterol, atherogenic index, liver index, and epididymal fat index were significantly increased, but the levels of high-density lipoprotein cholesterol, plasminogen activator inhibitor 1, and antiatherogenic index were decreased significantly in the model group compared to the control group ( P < .05, respectively). And these effects were reversed by treatment with repaglinide ( P < .05, respectively). Conclusion: Our results suggested that repaglinide may regulate the formation of early atherosclerosis through the abovementioned mechanisms.

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