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Objective To elucidate the mechanism of dl-3-N-butylphthalide (NBP) on renal ischemia-reperfusion injury (IRI) in rat models. Methods Forty SD rats were randomly divided into the sham operation group (Sham group), model group (IRI group), NF-κB inhibitor pyrrolidine dithiocarbamate group (PDTC group), low-dose NBP group (NBP-L group) and high-dose NBP group (NBP-H group), with 8 rats in each group. Serum creatinine (Scr), serum cystatin C(Cys-C), blood urea nitrogen (BUN) and serum interleukin (IL)-1β and IL-18 levels were detected in all groups. Pathological injury of renal tissues in each group was observed by Hematoxylin-eosin (HE) staining. The expression levels of inflammatory factors and nuclear factor (NF)-κB signaling pathway and cell pyroptosis-related proteins in renal tissues were measured by Western blot and immunohistochemical staining. Results Compared with the Sham group, renal tissue injury was more severe, and the levels of Scr, Cys-C, BUN and serum IL-1β and IL-18 were all up-regulated in the IRI group. Western blot showed that the relative expression levels of NOD-like receptor protein (NLRP3), Gasdermin D(GSDMD), cysteinyl aspartate specific proteinase (Caspase)-1, IL-18, IL-1β, NF-κB p65 and p-NF-κB p65 proteins were all up-regulated, and immunohistochemical staining revealed that the expression levels of NF-κB p65 and p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were all up-regulated in the IRI group. Compared with the IRI group, renal tissue injury was alleviated, and the levels of Scr, Cys-C, BUN and serum IL-18 and IL-1β were down-regulated in the PDTC, NBP-L and NBP-H groups. Western blot showed that the expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, IL-18, NF-κB p65 and p-NF-κB p65 proteins were down-regulated, and immunohistochemical staining indicated that the expression levels of NF-κB p65, p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were down-regulated in the PDTC, NBP-L and NBP-H groups, respectively. Compared with the NBP-L group, renal tissue injury was mitigated, and the levels of Scr, Cys-C, BUN, serum IL-18 and IL-1β were all down-regulated in the NBP-H group. Western blot showed the expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, IL-18, NF-κB p65 and p-NF-κB p65 proteins were down-regulated in the NBP-H group. Immunohistochemical staining indicated that the expression levels of NF-κB p65, p-NF-κB p65, IL-1β, IL-18 and NLRP3 proteins were down-regulated in the NBP-H group. Conclusions NBP may down-regulate the activity of NF-κB/NLRP3 signaling pathway and reduce the expression levels of cell pyroptosis-related proteins and inflammatory factors after renal IRI, thereby suppressing cell pyroptosis and alleviating renal IRI.
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Kidney ischemia-reperfusion injury (IRI) is the major cause of poor prognosis after kidney transplantation and partial nephrectomy. Besides, it is also a critical pathophysiological process of acute kidney injury. Consequently, the prevention and treatment of kidney IRI are of significance to improve clinical prognosis of recipients undergoing kidney transplantation. However, the mechanism underlying IRI is complex, and the exact mechanism remains elusive. Inflammation, as one of the main pathogenesis of IRI, plays a significant role in IRI-induced kidney injury. Nuclear factor (NF)-κB, as a rapid response transcription factor, has been proven to be involved in the regulation of inflammation during kidney IRI. Therefore, in this article, the structure of NF-κB, the activation pattern of NF-κB signaling pathway, the regulatory mechanisms of NF-κB upstream and downstream signaling pathways in kidney IRI were reviewed, and the role of NF-κB signaling pathway in kidney IRI was investigated, aiming to provide novel clinical ideas for the prevention and treatment of kidney IRI.
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Renal ischemia-reperfusion injury often occurs during operations that need to block the blood supply of the kidneys. It is an important pathophysiological process that affects the recovery of kidney function and causes acute renal failure. Activated NLRP3 inflammasome can mediate the maturation and release of a variety of pro-inflammatory factors, and participate in the inflammatory response in renal ischemia-reperfusion injury, thereby regulating body inflammation and related cell functions. This article summarized how NLRP3 inflammasome mediated the occurrence of inflammation in renal ischemia reperfusion injury, and further provied a new basis for the prevention and treatment of renal ischemia-reperfusion injury.
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Objective To investigate the effect and mechanism of artesunate on renal ischemia-reperfusion injury (IRI) in rat. Methods Twenty-five SD rats were randomly divided into the sham operation group (Sham group), model group (IRI group), low-dose artesunate group (ART-L group), high-dose artesunate group (ART-H group) and NLRP3 inflammasome inhibitor group (INF39 group), with 5 rats in each group. The levels of serum creatinine (Scr), blood urea nitrogen (BUN) and pathological damage of renal tissue were analyzed. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in serum were quantitatively measured. The expression level of IL-1β in renal tissues was determined by immunohistochemical staining. The expression levels of pyroptosis-related proteins were detected by fluorescent staining and Western blot. Results Compared with the Sham group, the levels of Scr and BUN were higher, the renal tissue injury was aggravated, the expression levels of TNF-α, IL-6 and IL-1βwere higher, and the expression levels of kidney injury molecule (KIM-1), pyroptosis-related protein NOD-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase (Caspase-1), Gasdermin D (GSDMD) and IL-1β proteins were higher in the IRI group. Compared with the IRI group, the levels of Scr and BUN were decreased, the renal tissue injury was mitigated, the expression levels of TNF-α, IL-6 and IL-1β were down-regulated, and the expression levels of KIM-1, NLRP3, Caspase-1, GSDMD and IL-1β proteins were down-regulated in the ART-L, ART-H and INF39 groups. Conclusions Artesunate may inhibit pyroptosis induced by NLRP3 inflammasome, down-regulate the expression levels of pyroptosis -related proteins, reduce the release of inflammatory factors after renal IRI and alleviate renal IRI.
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Renal ischemia-reperfusion injury (IRI) commonly occurs in renal transplantation, which is an important pathophysiological process that causes acute renal failure and severely affects clinical prognosis of the recipients. Inflammatory response plays a critical role in the pathogenesis and pathological process of IRI. Activated NOD-like receptor protein 3(NLRP3) inflammasome can mediate the maturation and release of various pro-inflammatory cytokines, thereby regulating the inflammatory response and relevant cell functions. In this article, the mechanism underlying NLRP3 inflammasome and its related inflammatory signaling pathway in renal IRI were reviewed, aiming to provide novel ideas for clinical prevention and treatment of renal IRI.
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OBJECTIVE: Total ceramide concentrations are linked with increased insulin resistance and cardiac dysfunction. However, recent studies have demonstrated that plasma concentrations of specific very-long-chain fatty ceramides (C24:0 and C22:0) are associated with a reduced incidence of coronary heart disease and all-cause mortality. We hypothesized that specific genetic loci are associated with plasma C22:0 and C24:0 concentrations.METHODS: Heritability and genome-wide association studies of plasma C24:0 and C22:0 ceramide concentrations were performed among 2,217 participants in the Framingham Heart Study Offspring Cohort, adjusting for cardiovascular risk factor covariates and cardiovascular drug treatment.RESULTS: The multivariable-adjusted heritability for C22:0 and C24:0 ceramides was 0.42 (standard error [SE], 0.07; p=1.8E-9) and 0.25 (SE, 0.08; p=0.00025), respectively. Nineteen single nucleotide polymorphisms (SNPs), all on chromosome 20, significantly associated with C22:0 concentrations; the closest gene to these variants was SPTLC3. The lead SNP (rs4814175) significantly associated with 3% lower plasma C22:0 concentrations (p=2.83E-11). Nine SNPs, all on chromosome 20 and close to SPTLC3, were significantly associated with C24:0 ceramide concentrations. All 9 were also significantly related to plasma C22:0 levels. The lead SNP (rs168622) was significantly associated with 10% lower plasma C24:0 ceramide concentrations (p=9.94E-09).CONCLUSION: SNPs near the SPTLC3 gene, which encodes serine palmitoyltransferase long chain base subunit 3 (SPTLC3; part of the enzyme that catalyzes the rate-limiting step of de novo sphingolipid synthesis) were associated with plasma C22:0 and C24:0 ceramide concentrations. These results are biologically plausible and suggest that SPTLC3 may be a potential therapeutic target for C24:0 and C22:0 ceramide modulation.
Subject(s)
Cardiovascular Diseases , Ceramides , Chromosomes, Human, Pair 20 , Cohort Studies , Coronary Disease , Genetic Loci , Genome-Wide Association Study , Genomics , Heart , Incidence , Insulin Resistance , Mortality , Plasma , Polymorphism, Single Nucleotide , Risk Factors , Serine C-PalmitoyltransferaseABSTRACT
Objective To investigate the effects of dexmedetomidine on postoperative cognitive dysfunction (POCD) in patients with obstructive sleep apnea. Methods A total of 50 patients with obstructive sleep apnea were divided into 2 groups: a dexmedetomidine group and a control group. Dexmedetomidine and 0.9% saline solution were given before and during the operation in the dexmedetomidine group and the control group respectively. MMSE scores were estimated at different time, and the concentration of serum S100β and NSE were detected before anesthesia at 3 h, 6 h, 24 h and 48 h after operation. Results One day after surgery, MMES score decreased significantly in both groups,of which MMES was notably higher in the DEX group than that in the control group (P<0.05). In both groups, S100βand NSE levels were significantly higher at T2, T3 and T4 than those at T1, and were the highest at T3 (P<0.05). S100β and NSE levels were significantly lower in the DEX group than those in the control group (P<0.05). Conclusion Dexmedetomidine can reduce the incidence of POCD in patients with obstructive sleep apnea. Its mechanism may relate to neuroprotection.
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Objective To evaluate the safety and efficacy of treating bifurcation lessions with jailed-balloon technique in simple strategy. Methods Ninety patients with bifurcation lessions (Duke D or F type) who received the side branch protection technique with simple strategy were involved in a single center retrospective analysis. Patients were randomly divided into jailed-balloon protection group (n=48) and jailed guidewire group (n=42). The process operating, procedural success of percutaneous coronary intervention (PCI) and percutaneous transluminal coronary angioplasty (PTCA), complications and the results of follow-up were investigated. Results The clinical baseline date and the bifurcation lesions were not significant different between jailed-balloon group and jailed guidewire group (P>0.05). The procedural success rate of PCI was 100%in jailed-balloon group and 97.6%in jailed guidewire group, no significance difference user between two groups (P>0.05). The perioperative complications (the rate of no reflow) was lower in jailed-balloon group than those of jailed guidewire group (1.0%vs. 19.0%, P0.05) and the maximum restenotic level (19.24%vs. 21.46%,P>0.05) in the main branch were not significant different between jailed-balloon group and jailed guidewire group. But the maximum restenotic level in the opening of side branch was lower in jailed-balloon group than that of jailed guidewire group (51.2% vs. 72.46%, P < 0.01). Conclusion The jailed-balloon technique reduces the operation complications, exposure time and amount of contrast agent, and also saves surgical consumables. The procedure of branch with simple strategy is safe and effective in treatment of bifurcation lesions.
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Objective To evaluate the correlation of Omentin-1, the high sensitivity C-reactive protein (hsCRP) and coronary heart disease (CHD). Methods Sixty-eight patients with CHD were divided into the unstable angina pectoris (UAP) group (n=36), stable angina pectoris (SAP) group (n=32). And 30 normal subjects without CHD diagnosed by coronary arteriography (CAG) were served as the control group. The serum level of Omentin-1 was measured by enzyme linked immu-nosorbent assay (ELISA) and the serum level of hsCRP was measured by turbidmetric immunoassay. Results The serum level of Omentin-1 was significantly lower, but the serum level of hsCRP was significantly higher in CHD group than that of control group (P0.05). The serum level of Omentin-1 was significantly lower in patients with single, double and three-vessel lesion group than that of control group, but the serum level of hsCRP was significantly higher in CHD group than that of control group (P0.05). The se-rum level of Omentin-1 was negatively correlated with serum level of hsCRP (P<0.01). Conclusion The serum level of Omentin-1 and hsCRP may correlate with CHD, but which may not reflect the severity of artery stenosis.
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Objective To investigate the efficacy of surgical treatment for hepatolithiasis in patients of advanced age.Methods The clinical data of 196 patients of advanced age (≥80 years) and with hepatolithiasis who were admitted to the Kailuan General Hospital from January 2009 to October 2012 were retrospectively analyzed.All the 196 patients received surgical treatment.Patients were followed up via phone call or out-patient examination till May 2013.Results Fifty-eight patients received emergent operation within 24 hours after admission,and the other 138 patients received operation 7.4 days (range,1.0-18.0 days) after admission.Fifty patients received laparoscopic surgery,including 43 received cholecystectomy + choledocholithotomy + T tube drainage,7 received choledocholithotomy + T tube drainage.One hundred and forty-six patients received open surgery,including 78 received cholecystectomy + choledocholithotomy + T tube drainage,43 received choledocholithotomy + T tube drainage and 25 received choledocholithotomy + T tube drainage + partial hepatectomy.The operation time was (78 ± 16)minutes,and the volume of intraoperative bleeding ranged between 15 mL and 300 mL.One hundred and ninety-four patients were cured and 2 patients died.Thirty-seven patients had complications after operation,with the morbidity of 18.88％ (37/196).A total of 163 patients were followed up,with the follow-up rate of 83.16％ (163/196).The median time of follow-up was 26 months (range,7-52 months).Twelve patients had hepatolithiasis recurrence,and the recurrence rate was 7.36％ (12/163).Conclusion Surgical treatment for hepatolithiasis in patients of advanced age has the advantages of high cure rate,low incidence of complications and recurrence,and the clinical efficacy is satisfactory.