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Objective To investigate the effects of lipopolysaccharide(LPS) on myelin phagocytosis during Wallerian degeneration after early peripheral nerve injury in rats.Methods Fifty male Wistar rats were recruited and randomly divided into LPS group(n=20),model group(n=20) and sham group(n=10).The right sciatic nerves of rats in the LPS and model groups were cut and sutured end-to-end,while the sciatic nerve of sham group rats were only exposed.Immediately after surgery,the rats in LPS group were given microinjections of LPS(2 g/L) into the surgical site in a final volume of 1 μL,and the rats in other two groups were injected with the same volume of saline.The sciatic nerves were taken at 1.5 h,24 h and 7d after surgery.Real-time quantitative PCR(qRT-PCR) was applied to detect the dynamic expressions of IL-1β mRNA and MCP-1 mRNA.Immunofluorescence staining was used to test the expression of CD68+ macrophages in sciatic nerves.HE staining was used to observe the pathological alterations of sciatic nerves tissue.ORO staining was used to observe sciatic nerves demyelination.LFB staining was used to detect the sciatic nerves myelin.Sciatic function index was used to evaluate the recovery of motor function in rats.Results Compared with the model group,qRT-PCR indicated that the expression of IL-1β and MCP-1 from LPS group were increased at 1.5 h and 24 h after surgery(P<0.001, P<0.001),respectively.Compared with the model group,the expression of CD68+ cells was increased significantly at 7th day after surgery(P<0.05).Histological examination showed that compared with the model group,a lot of inflammatory cells and Schwann cells were found at sciatic nerve stump in the LPS group at 7th day after operation.ORO staining showed that the degree of demyelination in the LPS group was higher than that in the model group.LFB staining showed that the sciatic nerve stump demyelination appeared in both model group and the LPS group at 7th day after operation,but compared with the model group,myelin debris clearance in the LPS group was significantly accelerated(P<0.05).Finally,compared with the model group,the SFI in the LPS group was increased significantly at 20 d after surgery(P<0.05).Conclusions The results confirm that LPS is possible to manipulate the innate immune response to accelerate myelin clearance during Wallerian degeneration after early peripheral nerve injury in rats.
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BACKGROUND:The mechanism underlying Wal erian degeneration fol owing peripheral nerve injury is complex. Immune regulation on Wal erian degeneration is beneficial for early repair of perpheral nerve injury. OBJECTIVE:To investigate the effects of Tol-like receptor 4 (TLR4) antagonist on Wal erian degeneration and axonal regeneration after early peripheral nerve injury in rats. METHODS:Fifty male Wistar rats were recruited and randomly divided into treatment group (n=20), model group (n=20) and sham group (n=10). The right sciatic nerves of rats in treatment and model groups were cut and sutured end-to-end, while the sciatic nerves of rats in sham group were only exposed. In the treatment group rats were intravenously injected with 0.15 mg/kg TAK-242 via tail vein 1 hour preoperatively and 7 days postoperatively, and the rats in the other two groups were given intravenous injection of the same volume of normal saline. The sciatic nerves were removed at 24 hours, 3, 4 and 7 days after surgery. RESULTS AND CONCLUSION:Real-time PCR indicated that the mRNA expressions of interleukin-1βand monocyte chemoattractant-1 were significantly increased in the model group compared with the sham group at 24 hours after surgery (both P<0.001), while the expressions were significantly decreased after TAK-242 injection (both P<0.001). Immunofluorescence showed that compared with the model group, down-regulated expression of CD68+and iba1+cel s appeared in the treatment group at 3 days after surgery (P<0.01, P<0.05). Luxol fast blue staining revealed that demyelination at the sciatic nerve stump appeared in both model and treatment groups at postoperative 7 days, but myelin debris clearance in the treatment group was significantly reduced compared with the model group (P<0.05). Hematoxylin-eosin staining showed that a lot of inflammatory cel s, Schwann cells and regenerated nerve fibers at the sciatic nerve stump were found in the model group, while there were few inflammatory cells, Schwann cel s and regenerated nerve fibers in the treatment group at 7 days after surgery. Immunohistochemistry found that the expression of growth-associated protein-43 in the treatment group was significantly lower than that in the model group at 4 days postoperatively (P<0.05). Besides, compared with the model group, a significantly decreased sciatic functional index was found in the treatment group at 20, 30 and 40 days after surgery (P<0.05). These results show that TLR4 antagonists delay early nerve regeneration in rats after sciatic nerve injury probably by inhibiting the TLR4 signaling pathway.
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Objective To investigate the application value of the transesophageal echocardiography TEE in patients with nonvalvular atrial fibrillation about the size lobes morphology and function of left atrial appendage LAA Methods One hundred and forty-two patients underwent TEE were divided into nonvalvular atrial fibrillation group 98 cases and non atrial fibrillation group 44 cases The orifice diameter depth volume peak emptying velocity PEV of the LAA and the 1 eft atrial dimension LAD were measured The form and lobes of LAA thrombus and spontaneous echo contrast SEC in LAA were observed Results The LAA orifice diameter depth volume and LAD of patients with atrial fibrillation were significantly higher than those in the group without atrial fibrillation which showed statistical significance P < 0 05 Forty-one cases in atrial fibrillation group were found with the SEC and the number with thrombus in LAA was 22 The differences of PEV between chicken wings and non-chicken wings were statistically significant P <0 05 The SEC in LAA and the lobe number of LAA had no relevance Conclusions It was reliable to analyze the size morphologies lobes and hemodynamic parameters of LAA in patients with atrial fibrillation by TEE which provided reference for percutaneous LAA occlusion and anticoagulation therapy for the patients with atrial fibrillation.
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Objective To investigate the effects of the FKBP51 · PHLPP · AKT signal module on the phosphorylation of Akt and hippocampal neuronal injury after the cerebral ischemia / reperfusion induced neuronal death in rat hippocampus.Methods Transient(15 min)brain ischemia was induced by the four-vessel occlusion in Sprague-Dawley rats.6 rats were used in each group.The antisense oligodeoxynucletides(AS ODN)of PHLPP2 (PH domain and leucine rich repeat protein phosphatases) was used to suppress the assembly of FKBP51 · PHLPP · Akt signal module by intracerebroventricular infusion once per day for 3 days before ischemia.After 6 hours reperfusion,interactions of PHLPP2 and FKBP51 (FK506 binding protein 5) with Akt were detected by immunoprecipitation (IP) and the phosphorylation of Akt was detected by western blot (IB).After 5 days reperfusion,rats were perfusion-fixed with paraformaldehyde and Hematoxylin-Eosin staining was used to examine the survival number of CA1 pyramidal cells of hippocampus.Results Compared to PHLPP2 MS ODN group(1.24±0.24,1.68±0.11,0.58±0.01),PHLPP2 AS ODN suppressed the assembly of the FKBP51 · PHLPP · Akt signaling module(1.06±0.01,1.04±0.13),and increased the phosphorylation of Akt(0.76±0.02) (P＜0.05).Furthermore,compared to PHLPP2 MS ODN group (20.1±2.5),the number of surviving neurons significantly increased in PHLPP2 AS ODN group(88.3±2.7)(P＜0.05).Conclusion The increasing assembly of FKBP51 · PHLPP · Akt signal module can damage CA1 pyramidal cells of hippocampus by inhibiting the phosphorylation level of Akt.
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Objective To investigate the neuralprotective effect of Rho kinase inhibitor fasudil hydrochloride in cerebral ischemia/reperfusion injury in rats.Methods The SD rats were randomly divided into four groups:the sham group,the ischemia/reperfusion group,the fasudil hydrochloride group and the physiological saline group.Fasudil hydrochloride were injected intraperitoneally 30 minutes before ischemia.And the physiological saline group were treated with the intraperitoneal injection of the same volume of saline.The phosphorylation and protein expression of GluR6 at 6 hours during reperfusion were detected using immunoprecipitation and immunoblotting analysis to examine the effect of Fasudil hydrochloride.Furthermore,TUNEL staining was used to examine the apoptosis of neurons in rat hippocampal CA1 regions after 3 days reperfusion.Results 1.Immunoprecipitation and immunoblotting analysis were used to analyze the phosphorylation of GluR6 in serine site.The results showed that the GluR6 serine phosphorylation level increased significantly at 6h of reperfusion compared with the sham group (P＜0.05).Fasudil hydrochloride group could inhibit the increased phosphorylation of GluR6 at 6h of reperfusion compared with the ischemia/reperfusion group and saline group,respectively (P ＜ 0.05).2.TUNEL staining was used to examine the apoptosis of neurons in 3 days after reperfusion in CA1 regions of hippocampus.The results indicated that significant numbers of TUNEL positive cells (40.20 ± 2.77) were observed 3 days after ischemia/reperfusion.The numbers of viable neurons per 1 mm length of CA1 pyramidal cells were quantitatively analyzed.Fasudil hydrochloride markedly decreased the neuronal loss compared with the ischemia/reperfusion group (19.80 ± 2.86) (P＜0.05).Conclusion Fasudil hydrochloride can inhibit induced phosphorylation of GluR6 by the ischemia/reperfusion.Fasudil hydrochloride can reduce the neurons apoptosis in hippocampal CA1 regions,and perform a neuralprotective effect on ischemia/reperfusion injury in rats.
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Objective To investigate the effects of sodium aescinate(SA)on oxidative stress and pulmonary function during acute exacerbation of chronic obstructive pulmonary disease(COPD).Methods One hundred and twenty patients with COPD were randomly divided into two groups:the control group(n =60) and the treatment group(n =60).All patients were treated with routine anti-infection,oxygen inhalation,relieving phlegm and anti-asthma The treatment group took SA in addition to the routine beteropathy.The changes of serum SOD,MDA,GSH-Px,T-AOC,pulmonary functions and 6 minute walk distance(6MWD) were detected before and after two-week treatment in patients of the two groups to compare with 60 healthy subjects.Results The total effective rate in the treatment group was 91.67％,while 76.67％ in the control group.The difference was statistically significant(x2 =5.065,P ＜0.05).Serum MDA level in both groups were comparatively higher than the healthy controls(9.25±1.55) μmol/L vs.(9.74±1.50) μmol/L vs.(2.06±0.29) μmol/L,P ＜0.001),while the levels of SOD,GSH-Px and T-AOC were lower than the healthy controls[SOD:(91.14±9.54) kU/L vs.(90.61±8.01) kU/L vs.(116.63±6.57) kU/L; GSH-Px:(139.38±36.56) U vs.(137.57±34.19) U/L vs.(189.34±35.54) U/L; T-AOC:(6.48±1.15) kU/L vs.(6.39±1.13) kU/L vs.(13.34±1.23)kU/L;P < 0.001].After treatment,all indexes of the two groups were obviously ameliorated in comparison with before treatment(P ＜ 0.001),but the level of MDA[(4.56±1.39) μmol/L]in the treatment group decreased more greatly than in the control groups(P ＜ 0.001).The levels of SOD[(103.85±7.07) kU/L],GSH-Px[(169.65±34.51) U/L],T-AOC[(10.52±1.09) KU/L],forced expiratory volume in 1 second/forced vital capacity(FEV1/FVC)[(60.49±6.11)％],FEVI％[(76.62±6.35)％]and 6MWD [(394.83±10.11)m]increased considerably more than those in the control group(P ＜ 0.001).Conclusion Oxidative stress might be involved in the course of acute exacerbation of COPD.Sodium aeseinate can improve the pulmonary functions by ameliorating the oxidative stress during acute exacerbation in patients with COPD.
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Objective To observe the effect of oxygen treatment plus non-invasive positive pressure ventilation on the stabillzation of chronic obstractive pulmonary disease and the influence on exercise tolerance.Methods The blood gas anylisis of and the result of 6 min walk test were observed and compared with self-control method.Results There was significant difference between the beginning and termination of the treatment in 10 patients haying finished the treatment and the results of 6 min walk test(P＜0.05).Conclusion The oxygen treatment plus non-invasive positive pressure ventilation in the stabilization of chronic obstructive pulmonary disease is safe and effective.