2-BFI Provides Neuroprotection Against Fluorosis by Stabilizing Endoplasmic Reticulum-Mitochondria Contact Sites and Inhibiting Activation of the NLRP3 Inflammasome.

2-(2-benzofu-ranyl)-2-imidazoline (2-BFI) is a drug that has attracted much attention in recent years. It has a therapeutic effect on brain diseases in animal models such as Alzheimer's disease and cerebral infarction. However, whether 2-BFI affords neuroprotection against the toxicity of fluoride, which can cross the blood-brain barrier and cause neurological dysfunction is not known. We investigated the cell viability and apoptosis of SH-SY5Y cells and primary cultures of cortical neurons exposed to fluoride, and 2-BFI was used to protect both two kinds of cells against the effects of fluoride. We found that 2-BFI can provide neuroprotection on SH-SY5Y cells and primary cultures of cortical neurons upon fluorosis by maintaining the stability of endoplasmic reticulum-mitochondria contact sites and inhibiting activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. This study may provide a new method for protecting against the neurotoxicity induced by fluoride exposure.

Acute hypoxia promotes the liver angiogenesis of largemouth bass (Micropterus salmoides) by HIF - Dependent pathway.

A 24-h hypoxia exposure experiment was conducted to determine how hypoxia exposure induce liver angiogenesis in largemouth bass. Nitrogen (N2) was pumped into water to exclude dissolved oxygen into 1.2 ± 0.2 mg/L, and liver tissues were sampled during hypoxia exposure of 0 h, 4 h, 8 h, 12 h, 24 h and re-oxygenation for 12 h. Firstly, the results showed that hypoxia exposure promoted the angiogenesis occurrence by immunohistochemical analysis of vascular endothelial growth factor receptor 2 (VEGFR2). Secondly, the concentration of vasodilation factor increased and it's activity was elevated during 8 h exposure, such as nitric oxide (NO) and nitric oxide synthase (NOS) (p < 0.05). Thirdly, hypoxia exposure promoted angiogenesis through up-regulation the expression of matrix metalloproteinase 2 (MMP-2), jagged, protein kinase B (AKT), phosphoinositide-3-kinase (PI3K), mitogen-activated protein kinase (MAPK) at 4 h; contrarily, the expression of inhibiting angiogenesis genes presented up-regulated at 8 h (p < 0.05), such as matrix metalloproteinase inhibitor-2 (TIMP-2), matrix metalloproteinase inhibitor-3 (TIMP-3). Finally, the genes and proteins that regulate angiogenesis presented obvious chronological order. Parts of them promoted the budding and extension of blood vessels were up-regulated during 4 h-8 h (p < 0.05), such as vascular endothelial growth factor a (VEGFA), VEGFR2, monocarboxylic acid transporter 1 (MCT1), CD147, prolyl hydroxylase (PHD), nuclear factor kappa-B (NF-κB); other part of them promoted blood vessel maturation were highly expressed during 12 h-24 h (p < 0.05), such as angiogenin-1 (Ang-1) and angiogenin-2 (Ang-2). In short, acute hypoxia can promote the liver angiogenesis of largemouth bass by HIF - dependent pathway.

The Role of ADAM17 in Inflammation-Related Atherosclerosis.

Atherosclerosis is a chronic inflammatory disease that poses a huge economic burden due to its extremely poor prognosis. Therefore, it is necessary to explore potential mechanisms to improve the prevention and treatment of atherosclerosis. A disintegrin and metalloprotease 17 (ADAM17) is a cell membrane-bound protein that performs a range of functions through membrane protein shedding and intracellular signaling. ADAM17-mediated inflammation has been identified to be an important contributor to atherosclerosis; however, the specific relationship between its multiple regulatory roles and the pathogenesis of atherosclerosis remains unclear. Here, we reviewed the activation, function, and regulation of ADAM17, described in detail the role of ADAM17-mediated inflammatory damage in atherosclerosis, and discussed several controversial points. We hope that these insights into ADAM17 biology will lead to rational management of atherosclerosis. ADAM17 promotes vascular inflammation in endothelial cells, smooth muscle cells, and macrophages, and regulates the occurrence and development of atherosclerosis.

Sinensetin Attenuates Amyloid Beta25-35-Induced Oxidative Stress, Inflammation, and Apoptosis in SH-SY5Y Cells Through the TLR4/NF-κB Signaling Pathway.

Sinensetin (SIN) is an important active compound that exists widely in citrus plants, and has been reported to exhibit various pharmacological properties, including anti-oxidative, anti-inflammatory, and anti-tumor. This study was designed to examine whether SIN can protect against amyloid beta (Aß)-induced neurotoxicity and to elucidate the underlying mechanism. Our results showed that pretreatment with SIN for 1 h, followed by co-treatment with Aß plus SIN for 24 h, attenuated Aß25-35-induced cell viability reduction, oxidative stress, inflammation, and apoptosis in a dose-dependent manner. Aß25-35-induced upregulation of Toll-like receptor 4 (TLR4) expression and nuclear translocation of nuclear factor-kappaB (NF-κB) p65 subunit were inhibited by pretreatment with SIN. Furthermore, the protective effect of SIN was abrogated by TLR4 overexpression. Hence, our data suggested that SIN attenuated Aß25-35-induced neurotoxicity through the TLR4/NF-κB pathway.

Comparison of single-injection ultrasound-guided thoracic paravertebral block with transversus abdominis plane block in peritoneal dialysis catheter implantation: a randomized controlled trial.

BACKGROUND: Previous study indicated that transversus abdominis plane (TAP) block could be the principal anesthetic technique for peritoneal dialysis catheter (PDC) implantations. However, a TAP block could not provide an optimal anesthetic effect on catheter exit site during PDC implantation. We hypothesized that single-injection ultrasound-guided thoracic paravertebral block (US-TPVB) could be the principal anesthetic technique with better pain relief at catheter exit site during PDC implantation, compared to a TAP block. And anesthesia quality of a single-injection US-TPVB was compared with that of a TAP block and local anesthetic infiltration (LAI). METHODS: Patients undergoing PDC implantations were randomized into groups TPVB or TAP or LAI. In group TPVB, single-injection US-TPVB at T10-T11 level was performed with 20 ml of 0.25% ropivacaine. In group TAP, oblique subcostal TAP block was performed with 20 ml of 0.25% ropivacaine. In group LAI, 40 ml of 0.25% ropivacaine was used. Anesthesia quality was compared among the three groups, including general anesthesia conversion rate, cumulative rescuing sufentanil consumption, and satisfaction rate by nephrologists and patients. RESULTS: Eighty-eight eligible patients were enrolled. Visual analogue scale (VAS) at most time points (except for the catheter exit site) were lower in group TAP, compared with group TPVB. VAS at parietal peritoneum manipulation was 6 (5, 7), 3 (0, 6), and 7 (4.75, 9) in groups TPVB, TAP, and LAI, respectively (P < 0.001). VAS at catheter exit site was 4 (3, 4), 5.5 (4, 8), and 5 (3, 7.25) in groups TPVB, TAP, and LAI, respectively (P = 0.005). Lower general anesthesia conversion rate, less cumulative rescuing sufentanil consumption, and higher satisfaction rates by nephrologists and patients were recorded in group TAP, compared with groups TPVB and LAI. CONCLUSIONS: Single-injection US-TPVB provided a better pain relief at catheter exit site. The quality and reliability of anesthesia after a single-injection US-TPVB was comparable to that of LAI, but not better than that of an oblique subcostal TAP block for PDC implantation. TRIAL REGISTRATION: TCTR20160911002 . Registered on 8 September 2016.

Ultrasonic extraction of anthocyanins from Lycium ruthenicum Murr. and its antioxidant activity.

The ultrasonic extraction (UE) technology, possessed the advantages of effective, energy-saving, and environmental-friendly, was applied to extract the anthocyanin from Lycium ruthenicum (LR). The extraction parameters of UE were optimized by response surface methodology (RSM) with Box-Behnken design (BBD). Anthocyanin composition in LR fruits grown in China was systematically identified and quantified by HPLC-ESI-MS. The result showed that PRG was the major anthocyanin, and delphinidin, petunidin, and malvidin were the major anthocyanidins in LR fruits. There was the same anthocyanin composition of LR and great variation in anthocyanins content of LR from different areas in China. However, there was no significant difference between wild and cultivated LR in the same region. A clear separation of LR according to geographical origins was revealed by hierarchical cluster analysis (HCA) and principal component analysis (PCA), and the discrimination model for the anthocyanin concentrations were developed using these two analysis methods. Furthermore, on-line HPLC-DPPH assay and scavenging activity of three kinds of radicals (DPPH·, ·OH, and O 2 - · ) in vitro were well applied to evaluate the antioxidant activity of the LR anthocyanin extract (LRAE). And its results indicated the LRAE could be a credible antioxidant agent for applications in cosmetics, food, and medicine.

Interactive effect of thermal and hypoxia on largemouth bass (Micropterus salmoides) gill and liver: Aggravation of oxidative stress, inhibition of immunity and promotion of cell apoptosis.

High temperatures and low oxygen in aquatic environments, such as intensive aquaculture or in natural watersheds, inevitably cause stress in fish. Fish are exposed to high temperatures during the summer, which exacerbates hypoxia. Hypoxia (1.2 ± 0.2 mg/L) under 20 °C (20 HG) and 26 °C (26 HG) was simulated to induce stress in largemouth bass (Micropterus salmoides). Related enzymes and genes involved in antioxidant, immune, and apoptotic responses were selected to explore the interactive effects of temperature and hypoxia on largemouth bass. The results showed that malondialdehyde (MDA) levels in plasma, gill, and liver increased in the 26 HG (p < 0.05). Liver superoxide dismutase (SOD) activity increased in the 26 HG. Peak SOD (SOD1, SOD2, SOD3a, and SOD3b), CAT, and GSH-Px mRNA levels in the gill and liver were observed at 12-24 h of stress. The levels of gill and liver total antioxidant capacity, catalase (CAT), glutathione peroxidase (GSH-Px) activities and other enzyme activities and genes in the 26 HG were higher than those in the 20 HG (p < 0.05). The gill and liver acid phosphatase and alkaline phosphatase activities increased with time in the 26 HG (p < 0.05), while gill and liver lysozyme activities in the 26 HG were lower than those in the 20 HG (p < 0.05). Tumor necrosis factor-α mRNA level was upregulated in the gill and downregulated in the liver at 24 h in the 26 HG. Interleukin (IL)-1ß and IL-8 mRNA levels were upregulated in the gill and liver in the 26 HG at 24 h, whereas IL-15 mRNA level was downregulated in the 26 HG at 12 h. Transforming growth factor-ß1 mRNA level was upregulated in the gill in the 20 HG at 24 h, but downregulated in gill and liver in the 26 HG at 24 h. Similarly, IL-10, Hepcidin-1, and Hepcidin-2 showed lower expression levels in the 26 HG. Gill and liver caspase-3 activities were higher in the 26 HG (p < 0.05), and gill caspase-3 activity was higher than that in the liver. The mRNA levels of proapoptotic genes (caspase-3, caspase-8, and caspase-9) were higher in the 26 HG. The present study demonstrates the interactive effects of temperature and hypoxia on stress in largemouth bass gill and liver. These results will be helpful to understand the mechanisms of stress induced by temperature and hypoxia in fish and provide a theoretical basis for aquaculture management.

Neuroprotective effect of angiotensin-(1-7) against rotenone-induced oxidative damage in CATH.a neurons.

There is evidence to support that ROSs are increased in Parkinson's disease (PD). Our recent research showed that angiotensin II (Ang II) participated in the pathogenesis of PD by triggering oxidative stress. Angiotensin-(1-7)[Ang-(1-7)] has been shown to moderate the adverse effects of the Ang II in many diseases. The purpose of the present study was to determine whether the Ang-(1-7) could have similar effects in CATH.a neurons. We used rotenone-induced neuron injury models to evaluate changes in cultured CATH.a cell lines levels of SOD, GSH and ROS. We also evaluated the expression of AT1, AT2, Mas receptors and Nox1, Nox2, P47phox, Hsp70 in treated with PBS, rotenone, Ang-(1-7), or Mas receptor antagonist A-779, alone and combined. The qRT-PCR and western blot were used to detect mRNA and protein levels of the AT1, AT2, Mas receptors and Nox1, Nox2, P47phox, Hsp70. The levels of SOD and GSH were determined by using commercial kits. The ROS generation was measured by the fluorescent probe assay. Ang-(1-7) in our current study significantly decreased rotenone-induced oxidative damage and increased the SOD and GSH generation. In addition, Ang-(1-7) significantly elevated Mas receptor expression and reduced NADPH oxidase activation, and these effects were completely eliminated by the A-779. Our findings suggest that Ang-(1-7) attenuates rotenone-induced oxidative damage in CATH.a neurons by activating the Mas receptor expression and inhibiting NADPH oxidase.

A Randomized Controlled Trial of Comparing Ultrasound-Guided Transversus Abdominis Plane Block with Local Anesthetic Infiltration in Peritoneal Dialysis Catheter Implantation.

BACKGROUND: The ultrasound-guided transversus abdominis plane (TAP) block has been demonstrated as a useful analgesia technique in lower-abdomen surgeries. We hypothesized that it could be the principal anesthesia technique for end-stage renal disease (ESRD) patients undergoing peritoneal dialysis (PD) catheter (PDC) implantation using the open dissection method. METHODS: This was a single-center, prospective, randomized, and double-blinded study. All eligible patients were randomized into 2 groups: the TAP block group (n = 20) and the local anesthetic infiltration (LAI) group (n = 20). RESULTS: Compared with the LAI group, the TAP block group revealed a remarkably lower visual analogue score, lower switching rate into general anesthesia, higher satisfaction rate, and less rescuing analgesic consumption during operation (p < 0.05). Both PD- and anesthesia-related complications were rare in the 4-week follow-up. CONCLUSIONS: The ultrasound-guided TAP block had better analgesic effect than LAI and can be used as a principal anesthesia technique for PDC implantation in ESRD patients without previous abdominal surgery.

Effects and Mechanisms of Radiofrequency Ablation of Renal Sympathetic Nerve on Anti-Hypertension in Canine / Efeitos e Mecanismos da Denervação Simpática Renal por Radiofrequência na Anti-Hipertensão em Cães

Abstract Background: Radiofrequency ablation of renal sympathetic nerve (RDN) shows effective BP reduction in hypertensive patients while the specific mechanisms remain unclear. Objective: We hypothesized that abnormal levels of norepinephrine (NE) and changes in NE-related enzymes and angiotensinconverting enzyme 2 (ACE2), angiotensin (Ang)-(1-7) and Mas receptor mediate the anti-hypertensive effects of RDN. Methods: Mean values of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were assessed at baseline and follow-up. Plasma and renal norepinephrine (NE) concentrations were determined using highperformance liquid chromatography with electrochemical detection, and levels of NE-related enzyme and ACE2-Ang(1-7)- Mas were measured using real time PCR, Western blot and immunohistochemistry or Elisa in a hypertensive canine model fed with high-fat diet and treated with RDN. The parameters were also determined in a sham group treated with renal arteriography and a control group fed with normal diet. Results: RDN decreased SBP, DBP, MAP, plasma and renal NE. Compared with the sham group, renal tyrosine hydroxylase (TH) expression was lower and renalase expression was higher in the RDN group. Compared with the control group, renal TH and catechol-o-methyl transferase (COMT) were higher and renalase was lower in the sham group. Moreover, renal ACE2, Ang-(1-7) and Mas levels of the RDN group were higher than those of the sham group, which were lower than those of the control group. Conclusion: RDN shows anti-hypertensive effect with reduced NE and activation of ACE2-Ang(1-7)-Mas, indicating that it may contribute to the anti-hypertensive effect of RDN.

Resumo Fundamentos: A denervação simpática renal por radiofrequência (DSR) mostra redução eficaz da pressão arterial (PA) de pacientes hipertensos, ainda que os mecanismos específicos permaneçam obscuros. Objetivo: Fizemos a hipótese de que níveis alterados de noradrenalina (NA) e mudanças nas enzimas relacionadas à NA e enzima conversora de angiotensina 2 (ECA-2), angiotensina (Ang)-(1-7) e receptor Mas são mediadores dos efeitos antihipertensivos da DSR. Métodos: Foram avaliados os valores médios de pressão arterial sistólica (PAS), pressão arterial diastólica (PAD) e pressão arterial média (PAM) no início e durante o seguimento. Foram medidas as concentrações plasmática e renal de noradrenalina (NA) por cromatografia líquida de alta eficiência com detecção eletroquímica, e os níveis de enzima relacionada à NA e ECA2-Ang-(1-7)-Mas através de PCR em tempo real, Western blot e imunohistoquímica ou Elisa em um modelo canino de hipertensão que recebeu ração rica em gordura e foi tratado com DSR. Os parâmetros também foram determinados em um grupo de cirurgia simulada submetido à arteriografia renal e em um grupo controle que recebeu dieta normal. Resultados: DSR causou diminuição da PAS, PAD, PAM e das concentrações plasmática e renal de NA. Em comparação ao grupo placebo, a expressão da tirosina hidroxilase (TH) renal foi menor e a da renalase foi maior no grupo DSR. Em comparação ao grupo controle, os níveis de TH renal e de catecol-o-metil-transferase (COMT) foram maiores e os de renalase foram menores no grupo cirurgia simulada. Além disso, os níveis renais de ECA2, Ang-(1-7) e Mas foram maiores no grupo DSR do que no grupo cirurgia simulada, que, por sua vez, foram menores do que no grupo controle. Conclusões: A DSR mostra efeitos anti-hipertensivos com redução da NA e ativação da ECA2-Ang-(1-7)-Mas, o que indica que pode contribuir com o efeito anti-hipertensivo da DSR.

Association between homocysteine and non-alcoholic fatty liver disease in Chinese adults: a cross-sectional study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and its prevalence is likely to rise even further. To help understand the pathogenesis and early prevention of progressive NAFLD, this large-scale study was designed to explore the potential association between homocysteine and the prevalence of NAFLD. METHODS: A total of 7203 subjects aged 18 years or older were enrolled in this cross-sectional study. The association of homocysteine with the prevalence of NAFLD, in the total sample and stratified by subgroups, was examined using multiple logistic regression analyses. RESULTS: Subjects in the higher quartiles of homocysteine had a higher prevalence of NAFLD. After multivariate adjustment, the odds ratio (OR) for NAFLD in the highest compared with the lowest quartile of homocysteine was 2.08 (95% confidence interval [CI] 1.61, 2.67). Moreover, in the subgroup analyses, we found an effect modification by gender, body mass index (BMI) and smoking status on the association between homocysteine and the prevalence of NAFLD (P for interaction: 0.001, 0.002 and <0.001, respectively). A stronger association was observed in female, obese and non-smoking adults than in male, normal weight and smoking subjects. CONCLUSION: Homocysteine was significantly associated with the prevalence of NAFLD, particularly in female, obese or non-smoking adults.

Therapeutic potential of umbilical cord mesenchymal stem cells in mice with acute hepatic failure.

BACKROUND/OBJECTIVE: Mesenchymal stem cells are probably one of the most promising alternatives for liver regeneration and repair. We present data supporting the ability of human umbilical cord mesenchymal stem cells (hUCMSCs) to generate hepatic elements and discuss the best transplantation pathway. METHODS: AHF mice were given hUCMSCs through tail-vein injection or into the liver lobes. Blood serum and liver tissues were collected to analyze the improvement of liver function and histological repair 24 h after hUCMSC administration. Real-time polymerase chain reaction and immunohistochemistry were used to detect the expression of human hepatocyte-specific markers in liver tissues. RESULTS: The results showed significant statistical differences in liver function after transplantation (P<.05). Real-time PCR and immunochemistry results demonstrated that the expression of hepatocyte-specific markers such as CK18 and AFP were obviously increased in the treatment groups through both transplantation pathways. Our data indicate that hUCMSCs are one of the stem cell candidates for liver repair because hUCMSCs can be easily and readily isolated and differentiated into hepatocytes both in vitro and in vivo. Additionally, tail-vein injection of hUCMSCs has a similar therapeutic efficacy but is more convenient compared to liver lobe injection. CONCLUSIONS: Our findings highlight the potential therapeutic value of hUCMSCs and show that cell transplantation through a peripheral vein is a safe and effective way to treat AHF mice. Furthermore, this method might mediate repair in patients with liver damage or disease in future clinical therapy.

Novel risk score of contrast-induced nephropathy after percutaneous coronary intervention.

AIM: Contrast-induced nephropathy (CIN) post-percutaneous coronary intervention (PCI) is a major cause of acute kidney injury. In this study, we established a comprehensive risk score model to assess risk of CIN after PCI procedure, which could be easily used in a clinical environment. METHODS: A total of 805 PCI patients, divided into analysis cohort (70%) and validation cohort (30%), were enrolled retrospectively in this study. Risk factors for CIN were identified using univariate analysis and multivariate logistic regression in the analysis cohort. Risk score model was developed based on multiple regression coefficients. Sensitivity and specificity of the new risk score system was validated in the validation cohort. Comparisons between the new risk score model and previous reported models were applied. RESULTS: The incidence of post-PCI CIN in the analysis cohort (n = 565) was 12%. Considerably high CIN incidence (50%) was observed in patients with chronic kidney disease (CKD). Age >75, body mass index (BMI) >25, myoglobin level, cardiac function level, hypoalbuminaemia, history of chronic kidney disease (CKD), Intra-aortic balloon pump (IABP) and peripheral vascular disease (PVD) were identified as independent risk factors of post-PCI CIN. A novel risk score model was established using multivariate regression coefficients, which showed highest sensitivity and specificity (0.917, 95%CI 0.877-0.957) compared with previous models. CONCLUSION: A new post-PCI CIN risk score model was developed based on a retrospective study of 805 patients. Application of this model might be helpful to predict CIN in patients undergoing PCI procedure.

Effects of NMDA-Receptor Antagonist on the Expressions of Bcl-2 and Bax in the Subventricular Zone of Neonatal Rats with Hypoxia-Ischemia Brain Damage.

Neonatal hypoxia-ischemia brain damage is an important cause of death by affecting prognosis of neural diseases. It is difficult to find effective methods of prevention and treatment due to the complexity of its pathogenesis. N-methyl-D-aspartate (NMDA), as an excitotoxicity amino acids, has proven to play an important role in hypoxic-ischemic. However, the exact effects of the NMDA subunits, NR2A and NR2B, during hypoxic-ischemic have not been investigated in detail. Therefore, we sought to study whether the NMDA receptor antagonist could confer neuroprotective effects in a neonatal rat hypoxia-ischemia model. The effects of intraperitoneal injections of different drugs, namely MK-801 (0.5 mg/kg), NVP-AAM077 (5 mg/kg), and Ro25-6981 (5 mg/kg), on the expressions of anti-apoptotic protein Bcl-2 and apoptosis protein Bax in the subventricular zone were analyzed by immunohistochemical staining to explore the roles of NMDA subunits (NR2A and NR2B) in hypoxic-ischemic. We found that the NR2B antagonist (Ro25-6981) could inhibit hypoxic-ischemic with the increasing Bcl-2 expression. NR2A antagonists (NVP-AAM077) can increase cerebral hypoxia-ischemia in neonatal rats, promoting the expression of apoptotic protein Bax.

Deoxynivalenol induces apoptosis in mouse thymic epithelial cells through mitochondria-mediated pathway.

Deoxynivalenol (DON) is a mycotoxin produced as a secondary metabolite by fungal species. In this report, we investigated the apoptotic effect of DON in mouse thymic epithelial cell line 1 (MTEC1). MTEC1 cell apoptosis induced by DON was confirmed by nuclei morphology change, TUNEL positive staining, annexin V/propidium iodide positive staining and increased protein levels of caspase-3, caspase-8, caspase-9 and poly(ADP-ribose) polymerase (PARP). The effects of DON on reactive oxygen species (ROS) levels and mitochondrial membrane potential were investigated via fluorescence microscope and flow cytometry, respectively. In addition, DON could significantly increase the protein levels of p53 and Bax/Bcl-2 ratio in MTEC1 cells. Taken together, our results suggest that DON causes the activation of p53, increased levels of ROS and the induction of mitochondrial dysfunction, which may contribute to DON-induced apoptosis in MTEC1 cells.

[Effect of renal sympathetic denervation on left ventricular hypertrophy and inflammatory factors in spontaneously hypertensive rats].

OBJECTIVE: To investigate the effect of renal sympathetic denervation on left ventricular hypertrophy and inflammatory factors in spontaneously hypertensive rats. METHODS: Thirty six spontaneously hypertensive rats (SHR) were divided into 3 groups with 12 animals in each group: SHR control group,operation group and sham operation group. Bilateral renal sympathectomy or sham operation were performed in operation and sham groups,respectively; another 12 WKY rats served as normal controls. The blood pressure and body weight were examined weekly. The animals were sacrificed at w1 and w6, rat hearts were collected and left ventricular mass index (LVMI) was calculated. The expression of TLR4,TNF-α and IL-6 in heart tissue were detected by immunohistochemistry and Western blot. RESULTS: The systolic blood pressure [(201.67 ± 11.09) mmHg compared with (140.0 ± 10.86)mmHg,P<0.05],diastolic blood pressure [(144.50 ± 10.48)mmHg compared with (78.50 ± 7.32)mmHg,P<0.05], LVMI (2.44 ± 0.05 compared with 1.93 ± 0.05,P<0.05),the expression of TLR4 (0.298 ± 0.004 compared with 0.126 ± 0.004, P<0.05), NF-κB (0.249 ± 0.006 compared with 0.195 ± 0.005, P<0.05),TNF-α(0.323 ± 0.004 compared with 0.146 ± 0.004,P <0.05), IL-6 (0.283 ± 0.005 compared with 0.207 ± 0.006, P<0.05) in SHR control group were significantly higher than those in WKY group. Compared to sham operation group,the systolic blood pressure (157.30 ± 9.35 compared with 197.30 ± 11.5, P<0.05),diastolic blood pressure (112.50 ± 6.25 compared with 146.80 ± 7.6, P<0.05),LVMI (2.32 ± 0.04 compared with 2.57 ± 0.09, P<0.05, TLR4 (0.198 ± 0.006 compared with 0.317 ± 0.008, P<0.05), NF-κB (0.208 ± 0.006 compared with 0.332 ± 0.007, P<0.05), TNF-α(0.27 ± 0.009 compared with 0.375 ± 0.004,P<0.05), IL-6 (0.218 ± 0.004 compared with 0.376 ± 0.009, P<0.05) in operation group were all decreased at w1 after sympathectomy. Six weeks after the operation,there were no significant differences in systolic blood pressure (197.50 ± 12.13 compared with 208.83 ± 10.23,P>0.05) and diastolic blood pressure (150.33 ± 7.74 compared with 151.50 ± 8.22, P>0.05) between denervated and sham-operated SHRs; however,the LVMI (2.46 ± 0.07 compared with 2.81 ± 0.05,P<0.05) and the expression of TLR4(0.301 ± 0.009 compared with 0.567 ± 0.006, P<0.05), NF-κB (0.251 ± 0.004 compared with 0.476 ± 0.009,P<0.05),TNF-α(0.324 ± 0.005 compared with 0.535 ± 0.006, P<0.05,IL-6 (0.285 ± 0.009 compared with 0.549 ± 0.007, P<0.05) in operation group were still significantly lower than those in sham operation group. CONCLUSION: Renal sympathetic denervation can significantly delay the progression of LVH in SHR, which may associated with lowering blood pressure and decreasing expression of TLR4, NF-κB,TNF-α, IL-6 in myocardial tissue.

Effect of renal denervation procedure on left ventricular hypertrophy of hypertensive rats and its mechanisms.

PURPOSE: To investigate the effect of renal denervation (RDN) on the blood pressure, left ventricular hypertrophy and myocardial expression of TLR4/NF-κB in spontaneously hypertensive rats (SHR). METHODS: A total of 36 SHR were randomly assigned into control group (D0), RDN group (D) and sham group (S). 12 WKY rats of same age served as controls (WKY group). Rats in the D0 and WKY groups were sacrificed, but rats in the D and S group were sacrificed at one week and six weeks after surgery. The heart was collected and the left ventricle weighted followed by calculation of left ventricular mass index (LVMI). RESULTS: In the D0 group, the blood pressure, LVMI and protein expression of TLR4, NF-κB, TNF-α and IL-6 in the myocardium were markedly higher than that in the WKY group (p<0.05). In the D1 and D2 group, the LVMI, NE and protein expression of TLR4, NF-κB, TNF-α and IL-6 in the myocardium were significantly reduced (p<0.05). CONCLUSION: Renal denervation can significantly delay the progression of left ventricular hypertrophy in spontaneously hypertensive rats, which may be attributed to the not only the suppression of sympathetic activity and attenuation of pressure load but the improvement of myocardial immuno-inflammation.

Impact of renal denervation on renalase expression in adult rats with spontaneous hypertension.

The aim of this study was to investigate the impact of renal denervation on the blood pressure, plasma renalase content and expression of renalase and tyrosine hydroxylase (TH) in the kidney of spontaneous hypertensive (SH) rats and to explore the mechanism of renal denervation involved in lowering blood pressure. SH rats (n=48) were randomly assigned to baseline, surgery (renal denervation), sham and control groups. WKY rats matched in age (n=12) served as the baseline control group. All rats were housed until they were 12 weeks old. The rats in the baseline group and the WKY group rats were sacrificed, and blood and kidney were collected for examination. In the renal denervation, sham and control groups, the blood pressure was continuously monitored. One and six weeks after renal denervation, 6 rats in each group were sacrificed, and blood and kidney were collected for examination. ELISA was employed to measure the plasma renalase, and western blot analysis was performed to detect the expression of TH and renalase in the kidney. Compared with the WKY rats, SH rats in the baseline group had significantly increased blood pressure and markedly elevated TH protein expression (P<0.05), but dramatically reduced plasma renalase content and protein expression of renalase in the kidney (P<0.05). One week after surgery, the mean arterial pressure and TH protein expression in the surgery group was lowered compared with the baseline group and dramatically reduced when compared with the sham and control groups (P<0.05). In the surgery group, renalase levels were markedly increased compared with the baseline, sham and control groups (P<0.05). Six weeks after renal denervation, the mean arterial pressure and TH levels in the surgery group were significantly increased while the renalase content and expression were markedly reduced compared with those at week 1, however, there were no marked differences among the surgery, sham and control groups (P>0.05). Moreover, no pronounced differences in the above variables were found between the sham and control groups at any timepoint (P>0.05). Renal denervation can lower blood pressure, which may be attributed to the suppression of sympathetic nerves, increase in plasma renalase content and renalase expression in the kidney.

Effect of renal denervation procedure on left ventricular hypertrophy of hypertensive rats and its mechanisms / Efeito da denervação renal na hipertrofia do ventrículo esquerdo de ratos hipertensos e seu mecanismo

PURPOSE: To investigate the effect of renal denervation (RDN) on the blood pressure, left ventricular hypertrophy and myocardial expression of TLR4/NF-κB in spontaneously hypertensive rats (SHR). METHODS: A total of 36 SHR were randomly assigned into control group (D0), RDN group (D) and sham group (S). 12 WKY rats of same age served as controls (WKY group). Rats in the D0 and WKY groups were sacrificed, but rats in the D and S group were sacrificed at one week and six weeks after surgery. The heart was collected and the left ventricle weighted followed by calculation of left ventricular mass index (LVMI). RESULTS: In the D0 group, the blood pressure, LVMI and protein expression of TLR4, NF-κB, TNF-α and IL-6 in the myocardium were markedly higher than that in the WKY group (p<0.05). In the D1 and D2 group, the LVMI, NE and protein expression of TLR4, NF-κB, TNF-α and IL-6 in the myocardium were significantly reduced (p<0.05). CONCLUSION: Renal denervation can significantly delay the progression of left ventricular hypertrophy in spontaneously hypertensive rats, which may be attributed to the not only the suppression of sympathetic activity and attenuation of pressure load but the improvement of myocardial immuno-inflammation.

OBJETIVO: Investigar o efeito da denervação renal na pressão sanguínea, na hipertrofia do ventrículo esquerdo e a expressão miocárdica de TLR4/NF-kB em ratos espontaneamente hipertensos. MÉTODOS: Trinta e seis SHR ratos foram aleatoriamente distribuídos em grupo controle, grupo denervação renal (D) e grupo sham(S). 12 WKY ratos de mesma idade serviram de controle. Os ratos controles foram sacrificados, mas os ratos com denervação renal e sham foram sacrificados uma semana e seis semanas após a cirurgia. O coração foi retirado e o ventrículo esquerdo pesado seguido pelo cálculo da massa ventricular (LVMI). RESULTADOS: No grupo DO, a pressão sanguínea, LVMI e a expressão proteica de TLR4, NF-κB, TNF-α e IL-6, no miocárdio foram marcadamente maiores do que o grupo WKY (p<0,05). Nos grupos D1 e D2, o LVMI, NE e a expressão proteica de TLR4, NF-κB, TNF-α e IL-6 no miocárdio foi significantemente reduzido (p<0,05). CONCLUSÃO: A denervação renal pode significantemente retardar a progressão da hipertrofia ventricular esquerda em ratos espontaneamente hipertensos, o que pode ser atribuído não apenas pela supressão da atividade simpática e atenuação da pressão, mas pela melhora na imunoinflamação miocárdica.

[Impact of renal denervation on expression of renalase and tyrosine hydroxylase in adult rats with spontaneous hypertension].

OBJECTIVE: To investigate the impact of renal denervation on the blood pressure, plasma renalase content and expression of renalase and tyrosine hydroxylase (TH) in the idney of spontaneous hypertensive (SH) rats and to explore the role of renal denervation in lowering the blood pressure. METHODS: SH rats were randomly assigned into a baseline group, a surgery (renal denervation) group, a sham group and a control group (n=48). WKY rats matched in age (n=12) served as a baseline control group. All rats were housed until 12 weeks old. Then, the rats in the baseline group and the WKY group were sacrificed whose blood and kidney were collected for examination. In the renal denervation group, the sham group and the control group, the blood pressure was monitored continuously. One week and 6 weeks after the renal denervation, 6 rats in each group were sacrificed whose blood and kidney were collected. ELISA was employed to measure the plasma renalase and Western blot assay done to detect the expression of TH and renalase in the kidney. RESULTS: Compared with WKY rats, blood pressure significantly increased and TH protein expression markedly elevated (P<0.05) in SH rats in the baseline group, but plasma renalase content and protein expression of renalase in the kidney dramatically reduced (P<0.05). One week after the surgery, the mean arterial pressure and TH protein expression in the surgery group were lowered compared with the baseline group and dramatically reduced compared with the sham group and the control group (P<0.05). In the surgery group, the renalase level was markedly increased compared with the baseline group, the sham group, and the control group (P<0.05). Six weeks after the renal denervation, the mean arterial pressure and TH level in the surgery group were significantly increased but the renalase content and expression markedly reduced compared with those 1 week, but there were no marked differences among the surgery group, the sham group, and the control group (P>0.05). No pronounced differences in the above variables were found between the sham group and the control group at any time point (P>0.05). CONCLUSION: Renal denervation can lower the blood pressure, which may attribute to the suppression of sympathetic nerves, increase in plasma renalase content and renalase expression in the kidney.