scholarly journals Effects of dexmedetomidine on the RhoA /ROCK/ Nox4 signaling pathway in renal fibrosis of diabetic rats

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 890-898 ◽  
Author(s):  
Chen Jihua ◽  
Chen Cai ◽  
Bao Xubin ◽  
Yu Yue
Keyword(s):  
Renal Function ◽  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Rat Kidney ◽  
Diabetic Rats ◽  
Immunohistochemical Method ◽  
Model Group ◽  
Protein Expressions ◽  
Masson Staining

AbstractObjectiveTo investigate the effects and mechanisms of dexmedetomidine (Dex) on model rats of diabetic nephropathy (DN).MethodsRats were divided into NC, model, Dex-L (1μg/ kg), Dex-M (5μg/kg) and Dex-H (10μg/kg) groups. Rats in all groups except in the NC group were injected with streptozotocin (STZ) combined with right nephrectomy. Rats in Dex (1, 5 and 10μg/kg) groups received gavage with Dex (1, 5 and 10μg/kg). After 4 weeks, rats were sacrificed and kidneys were collected. HE staining was performed for a renal injury. Masson staining was applied to detect the fibrotic accumulation in rat kidney. Radioimmunoassay was used to test the renal function. Immunohistochemical method was used to detect protein expressions of RhoA, p-MYPT and Nox4 in rat kidney.ResultsCompared with the NC group, the levels of urine microalbumin in protein, α1-MG and β2-MG, renal fibrotic accumulation, RhoA, p-MYPT, Nox4 and α-SMA in model group increased significantly (P＜0.001, respectively). Compared with the model group, Dex low, medium and high groups improved the deposition of renal fiber in rats, inhibited the expression levels of microalbumin, α1-MG and β2-MG in urine and decreased expression of RhoA, p-MYPT, Nox4 and α-SMA proteins (P＜0.05, P＜0.01).ConclusionDex is possible to inhibit the expression of α-SMA and renal fibrous substance deposition in rat kidney via RhoA/ROCK/Nox4 signaling pathway, thereby reducing early kidney damage in model rats.

scholarly journals The role of nicotinamide in the correction of renal function in diabetic nephropathy

2019 ◽  
Vol 23 (2) ◽  
pp. 218-221
Author(s):  
L. V. Yanitskaya ◽  
L. F. Osinskaya ◽  
A. V. Redko
Keyword(s):  
Diabetes Mellitus ◽  
Body Weight ◽  
Diabetic Nephropathy ◽  
Statistical Analysis ◽  
Rat Kidney ◽  
Clinical Manifestations ◽  
Diabetic Rats ◽  
Cortical Layer ◽  
The Difference

Hyperglycemia of diabetes mellitus leads to the activation of the polyol way of oxidation of glucose with the activation of the enzymes of aldose reductase and sorbitol dehydrogenase and of their coenzymes NADPH and NAD, which triggers the mechanism of formation of sorbitol. The consequences of these changes lead to microangiopathy of the tissues of the kidneys, which may be one of the pathogenetic mechanisms of diabetic nephropathy. In an accessible literature, the role of coenzymes of sorbitol pathway in the development of diabetic nephropathy is not sufficiently defined. The purpose of the study was to study the content of NAD and NADPH coenzymes, their correlation, and their role in the mechanism of kidney damage in diabetes mellitus and to predict the possible correction of these changes with the NAD-nicotinamide derivative. The study was conducted on a model of streptotrozectinic diabetes mellitus (single administration of streptozotocin in a dose of 60 mg per 1 kg of body weight). Four weeks after induction of diabetes, nicotinamide (100 mg per 1 kg body weight) was injected. The level of glucose was determined by the Accu-chek (Roshe Diagnostics, Switzerland) glucose meter. The content of NAD and NADH was determined in the non-protein extracts. The statistical analysis was carried out using the Microsoft Excel statistical analysis program. The difference between the indicators was considered statistically significant (p<0.05). The NAD level was reduced by 31%, the NAD/NADN ratio was 32%. The dependence of the ratio of NADP/NADPN in conditions of hyperglycemia of diabetes mellitus with clinical manifestations of diabetic nephropathy is determined. A decrease in the ratio of NADP/NADPN to 38% in the rat kidney in the cortical layer was detected. The introduction of nicotinamide normalized the reduced content of NAD diabetic rats. These results provide perspectives for further research in which nicotinamide can be used as a renal protector.

scholarly journals miR-136 improves renal fibrosis in diabetic rats by targeting down-regulation of tyrosine kinase SYK and inhibition of TGF-β1/Smad3 signaling pathway

Renal Failure ◽  
2020 ◽  
Vol 42 (1) ◽  
pp. 513-522 ◽  
Author(s):  
Lei Liu ◽  
Xinlu Pang ◽  
Wenjun Shang ◽  
Guiwen Feng ◽  
Zhigang Wang ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Diabetic Rats ◽  
Down Regulation ◽  
Tgf Β1

Sildenafil, a phosphodiesterase type 5 inhibitor, attenuates diabetic nephropathy in STZ-induced diabetic rats

2016 ◽  
Vol 27 (1) ◽  
Author(s):  
Alok Shiomurti Tripathi ◽  
Papiya Mitra Mazumder ◽  
Anil Vilasrao Chandewar
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Diabetic Nephropathy ◽  
Triglyceride Level ◽  
Biochemical Parameters ◽  
Treated Group ◽  
Diabetic Rats ◽  
Treatment Results ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Phosphodiesterase Type

AbstractThe present study evaluates the possible mechanism of sildenafil citrate (SIL) for the attenuation of renal failure in diabetic nephropathic (DN) animals.Diabetic nephropathy was induced by a single dose of streptozotocin (STZ) (60 mg/kg, i.p.) and confirmed by assessing the blood and urine biochemical parameters on the 28th day of its induction. The selected DN animals were treated with glimepiride (0.5 mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) for a period of 6 weeks. Biochemical parameters in blood and urine were estimated after the 29th and 70th day of the protocol for the estimation of the effect of SIL.There were significant alterations in the blood and urine biochemical parameters in STZ-treated groups which confirmed DN. There was a significant decrease in the triglyceride level in the SIL-only-treated group on the 70th day of the protocol. The histopathology study also suggested that SIL treatment results in the improvement in the podocyte count in DN animals.The present study concludes that SIL improves the renal function by decreasing the triglyceride level and improving the podocyte count in DN animals.

scholarly journals Buyang Huanwu Decoction protects against STZ-induced diabetic nephropathy by inhibiting TGF-β/Smad3 signaling-mediated renal fibrosis and inflammation

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Weifeng Wu ◽  
Yifan Wang ◽  
Haidi Li ◽  
Haiyong Chen ◽  
Jiangang Shen
Keyword(s):  
Renal Function ◽  
Diabetic Nephropathy ◽  
High Glucose ◽  
Renal Fibrosis ◽  
Mesangial Cells ◽  
Buyang Huanwu Decoction ◽  
Active Compounds ◽  
Renal Inflammation ◽  
Pas Staining ◽  
Tgf Β1

Abstract Background Buyang Huanwu Decoction (BHD) is a classical Chinese Medicine formula empirically used for diabetic nephropathy (DN). However, its therapeutic efficacies and the underlying mechanisms remain obscure. In our study, we aim to evaluate the renoprotective effect of BHD on a streptozotocin (STZ)-induced diabetic nephropathy mouse model and explore the potential underlying mechanism in mouse mesangial cells (MCs) treated with high glucose in vitro, followed by screening the active compounds in BHD. Methods Mice were received 50 mg/kg streptozotocin (STZ) or citrate buffer intraperitoneally for 5 consecutive days. BHD was intragastrically administrated for 12 weeks starting from week 4 after the diabetes induction. The quality control and quantitative analysis of BHD were studied by high-performance liquid chromatography (HPLC). Renal function was evaluated by urinary albumin excretion (UAE) using ELISA. The mesangial matrix expansion and renal fibrosis were measured using periodic acid-schiff (PAS) staining and Masson Trichrome staining. Mouse mesangial cells (MCs) were employed to study molecular mechanisms. Results We found that the impaired renal function in diabetic nephropathy was significantly restored by BHD, as indicated by the decreased UAE without affecting the blood glucose level. Consistently, BHD markedly alleviated STZ-induced diabetic glomerulosclerosis and tubulointerstitial injury as shown by PAS staining, accompanied by a reduction of renal inflammation and fibrosis. Mechanistically, BHD inhibited the activation of TGF-β1/Smad3 and NF-κB signaling in diabetic nephropathy while suppressing Arkadia expression and restoring renal Smad7. We further found that calycosin-7-glucoside (CG) was one of the active compounds from BHD, which significantly suppressed high glucose-induced inflammation and fibrosis by inhibiting TGF-β1/Smad3 and NF-κB signaling pathways in mesangial cells. Conclusion BHD could attenuate renal fibrosis and inflammation in STZ-induced diabetic kidneys via inhibiting TGF-β1/Smad3 and NF-κB signaling while suppressing the Arkadia and restoring renal Smad7. CG could be one of the active compounds in BHD to suppress renal inflammation and fibrosis in diabetic nephropathy.

The Molecular Mechanism of Scutellaria baicalensis Georgi Stems and Leaves Flavonoids in Promoting Neurogenesis and Improving Memory Impairment by the PI3K-AKT-CREB Signaling Pathway in Rats

2021 ◽  
Vol 24 ◽  
Author(s):  
Qian-qian Liu ◽  
Sheng-kai Ding ◽  
Hui Zhang ◽  
Ya-zhen Shang
Keyword(s):  
Cerebral Cortex ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Memory Impairment ◽  
Model Group ◽  
Memory Errors ◽  
Scutellaria Baicalensis Georgi ◽  
Protein Expressions ◽  
Stems And Leaves

Aim: The aim of this study was to investigate the effect, and molecular mechanism of Scutellaria Baicalensis Georgi stems and leaves flavonoids (SSF) in promoting neurogenesis and improving memory impairment induced by the PI3K-AKT-CREB signaling pathway. Methods: Alzheimer's disease (AD) was induced in the male Wistar rats by intracerebroventricular injection of amyloid beta-peptide 25-35 (Aβ25-35) in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1(RHTGF-β1) (composited Aβ). The Morris water maze was used to screen the successful establishment of the memory impairment model of rats. The screened successful model rats were randomly divided into a model group and three groups of three different doses of the drug (SSF). Rats in the drug group were treated with 35, 70, and 140 mg/kg of SSF for 43 days. The Eight-arm maze was used to measure the spatial learning and memory abilities of the rat, including working memory errors (WME) and reference memory errors (RME). Immunohistochemistry was used to detect the expression of BrdU, an indicator of neuronal proliferation, in the hippocampal gyrus of rats. The mRNA and protein expressions of TRKB, PI3K, AKT, P-AKT, and IGF2 in the PI3K-AKT-CREB signaling pathway in the hippocampus and cerebral cortex of the rats were determined by quantitative real-time PCR (qPCR) and Western blotting methods. Results: Compared to the sham group, the spatial memory ability of rats with composited Aβ was decreased, the number of WME and RME (P < 0.01) was increased, the expression of BrdU protein (P < 0.01) in the hippocampal gyrus was reduced, the mRNA and protein expression levels of TRKB, AKT, and IGF2 (P < 0.01, P < 0.05) in the hippocampus and cerebral cortex were lowered, and the mRNA expression level of PI3K (P < 0.01) in the cerebral cortex and the protein expression level of PI3K (P < 0.01) in the hippocampus were augmented. However, compared to the model group, the three-doses of SSF improved memory disorder induced by composited Aβ, reduced the number of WME and RME, increased the expression of BrdU protein in the hippocampal gyrus, and differently regulated the mRNA and protein expressions in composited Aβ rats. Conclusions: SSF improved memory impairment and neurogenesis disorder induced by composited Aβ in rats by activating the PI3K-AKT-CREB signaling pathway and up-regulating the mRNA and protein expressions of TRKB, PI3K, AKT, CREB, and IGF2.

Effect of acupuncture on neurovascular units after cerebral infarction in rats through PI3K/AKT signaling pathway

2020 ◽  
Vol 75 (4) ◽  
pp. 387-397
Author(s):  
Linlin Wei ◽  
Kexue Zeng ◽  
Juanjuan Gai ◽  
Feixiong Zhou ◽  
Zhenglin Wei ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Signaling Pathway ◽  
Sham Group ◽  
Escape Latency ◽  
Akt Signaling ◽  
Acupuncture Group ◽  
Akt Signaling Pathway ◽  
Model Group ◽  
Protein Expressions ◽  
The Times

OBJECTIVE: To study the effect of acupuncture on neurovascular units after cerebral infarction (CI) in rats through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signaling pathway. METHODS: A total of 36 Sprague-Dawley rats were randomly divided into sham group (n = 12), model group (n = 12) and acupuncture group (n = 12). The external carotid artery was only exposed in model group, while the post-CI ischemia-reperfusion model was established using the suture method in the other 2 groups. After modeling, the rats in sham group and model group were fixed and sampled, while those in acupuncture group were treated with acupuncture intervention for 2 weeks and sampled. The neurological deficits of rats were evaluated using the Zea-Longa score, and the spatial learning and memory of rats were detected via water maze test. Moreover, the expressions of vascular endothelial growth factor (VEGF), growth associated protein-43 (GAP-43) and synuclein (SYN) in brain tissues were detected via immunohistochemistry, and the relative protein expressions of PI3K p85, PI3K p110 and p-AKT were detected via Western blotting. The messenger ribonucleic acid (mRNA) expressions of VEGF, GAP-43 and SYN were detected via quantitative polymerase chain reaction (qPCR). RESULTS: The Zea-Longa score was significantly increased in model group and acupuncture group compared with that in sham group (p < 0.05), while it significantly declined in acupuncture group compared with that in model group (p < 0.05). The escape latency was significantly prolonged and the times of crossing platform were significantly reduced in model group and acupuncture group compared with those in sham group (p < 0.05), while the escape latency was significantly shortened and the times of crossing platform were significantly increased in acupuncture group compared with those in model group (p < 0.05). The positive expressions of VEGF, GAP-43 and SYN were obviously increased in model group and acupuncture group compared with those in sham group (p < 0.05), while they were obviously increased in acupuncture group compared with those in model group (p < 0.05). Besides, model group and acupuncture group had significantly higher relative protein expressions of PI3K p85, PI3K p110 and p-AKT than sham group (p < 0.05), while acupuncture group also had significantly higher relative protein expressions of PI3K p85, PI3K p110 and p-AKT than model group (p < 0.05). The relative mRNA expressions of VEGF, GAP-43 and SYN were remarkably increased in model group and acupuncture group compared with those in sham group (p < 0.05), while they were remarkably increased in acupuncture group compared with those in model group (p < 0.05). CONCLUSION: Acupuncture promotes the repair of neurovascular units after CI in rats through activating the PI3K/AKT signaling pathway, thereby exerting a protective effect on neurovascular units.

scholarly journals Exercise Training Alleviates Cognitive Functions in Diabetic Rats through HMGB1/RAGE/NF-kB Pathway

2021 ◽  
Author(s):  
Wang yan ◽  
wang chengji
Keyword(s):  
Blood Glucose ◽  
Exercise Training ◽  
Glycated Hemoglobin ◽  
Escape Latency ◽  
Exercise Group ◽  
Diabetic Rats ◽  
Control Group ◽  
Model Group ◽  
Protein Expressions ◽  
Probe Distance

Abstract Objective: To observe the effect of exercise training on cognitive functions of diabetic rat model. Methods: Male SD rats were given a high fat and high sugar diet, except for control group. After 4 weeks, 35 mg /kg STZ was intraperitoneally injected to establish type 2 diabetes model rats. After successful modeling, rats were randomly divided into the model group, model + exercise group. Animals performed 5 days of consecutive treadmill exercise (60 min/day) with 22 m/min speeds for 60 days. After 60 days, behavioral tests were conducted by Morris water maze method. then rats were weighed and blood samples were obtained to detect blood glucose. Some animals were sacrificed to prepare serum to detect glycosylated hemoglobin. Brain tissues were taken to detect the protein expressions of HMGB1-/RAGE-/NF-κB signal pathway by Western Blot. The brains of other animals were perfused and taken for RAGE and NF-κB immunohistochemical staining.Results: Compared with control group, escape latency and probe distance in the model group were significantly prolonged, swimming time in the target quadrant was significantly shortened, and the number of crossing platform was significantly reduced. The average grayvalues of NF-κB and RAGE were significantly decreased. Expressions of HMGB1,RAGE,p-NF-кBp65 and p-IкBα were significantly up-regulated(P<0.05 or P<0.01). Compared with the model group, escape latency and probe distance were significantly shortened, swimming time in the target quadrant was prolonged and increased the number of crossing platform, it also reduced the fasting blood glucose, increased body weights, reduced the level of glycated hemoglobin, and significantly increased the mean grayvalues of NF-κB and RAGE. The protein expressions of HMGB1, RAGE, p-NF-кBp65 and p-IкBα were decreased in model + exercise group.Conclusion: Exercise training can ameliorate the cognitive dysfunction of diabetic rats, its mechanism may be related to reducing blood glucose, reducing the level of glycated hemoglobin and improving the HMGB1 /RAGE/NF-κB pathway in the brain tissue.

Triptolide Improves Renal Injury in Diabetic Nephropathy Rats through TGF-β1/Smads Signal Pathway

2020 ◽  
Vol 20 ◽  
Author(s):  
Ruoyu Pang ◽  
Donghai Gu
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Injury ◽  
Diabetic Rats ◽  
Control Group ◽  
Inflammatory Factor ◽  
Group Model ◽  
Model Group ◽  
Tnf Α ◽  
Smad7 Expression ◽  
Tgf Β1

Objective: To investigate the therapeutic effect and mechanism of Triptolide on renal injury in diabetic nephropathy rats. Methods: A total of 15 male SD rats aged 8 weeks were randomly divided into five groups (3 rats in each group): control group, model group, Triptolide low-dose (Triptolide-L) group, Triptolide medium-dose (Triptolide-M) group, Triptolide high-dose (Triptolide-H) group. The rats models of diabetic nephropathy (DN) were established by a single intraperitoneal injection of STZ after being fed with high-fat and high-sugar diet for 4 weeks, and the fasting blood glucose (FBG) concentration of rats was detected. After 4 weeks, HE-staining was used to evaluate the renal pathological damage in rats; biochemical analysis was used to determine the blood urea nitrogen (BUN), serum creatinine (SCr), total cholesterol (TC), triglyceride (TG); ELISA was used to measure the serum inflammatory factor levels; Western blot (WB) was used to detect the expression of TGF-β1/Smads pathway proteins. Results: In the four FBG tests (once a week), the FBG concentration in the model group was significantly higher than that in the control group, while Triptolide-treated rats were significantly lower than that in the model group. Rats in Model group showed obvious renal injury, and Triptolide significantly improved the renal injury in DN rats. Compared with the control group, the expression of BUN, SCr, TC, TG, inflammatory factors TNF-α, IL-6 and IL-1β in the model group increased significantly. WB results showed that the expressions of TGF-β1, Smad3, α-SMA and vimentin in the kidney significantly increased, while the Smad7 expression significantly decreased. Triptolide significantly reduced the levels of BUN, SCr, TC, TG and TNF-α, IL-6, IL-1β in diabetic rats, decreased the expression of TGF-β1, Smad3, α-SMA, vimentin, and increased the Smad7 expression. In different doses of Triptolide treatment group, its effect showed a significant concentration dependence. Conclusion: Triptolide alleviates renal injury in diabetic rats by inhibiting the TGF-β1/Smads signaling pathway.

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