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The present study was designed to investigate the mechanisms by which P2X7 receptors (P2X7Rs) mediate the activation of vasopressinergic neurons thereby increasing sympathetic hyperactivity in the paraventricular nucleus (PVN) of the hypothalamus of rats with acute myocardial ischemia (AMI). The left anterior descending branch of the coronary artery was ligated to induce AMI in rats. The rats were pretreated with BBG (brilliant blue G, a P2X7R antagonist), nelivaptan (a vasopressin V1b receptor antagonist), or diphenyleneiodonium (DPI) [an nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor]. Hemodynamic parameters of the heart were monitored. Myocardial injury and cardiomyocyte apoptosis were assessed. In the PVN of AMI rats, P2X7R mediated microglial activation, while reactive oxygen species (ROS) and NADPH oxidase 2 (NOX2) were higher than in the sham group. Intraperitoneal injection of BBG effectively reduced ROS production and vasopressin expression in the PVN of AMI rats. Moreover, both BBG and DPI pretreatment effectively reduced sympathetic hyperactivity and ameliorated AMI injury, as represented by reduced inflammation and apoptosis of cardiomyocytes. Furthermore, microinjection of nelivaptan into the PVN improved cardiac function and reduced the norepinephrine (AE) levels in AMI rats. Collectively, the results suggest that, within the PVN of AMI rats, P2X7R upregulation mediates microglial activation and the overproduction of ROS, which in turn activates vasopressinergic neuron-V1b receptors and sympathetic hyperactivity, hence aggravating myocardial injury in the AMI setting.
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Increased microglial activation and neuroinflammation within autonomic brain regions such as the rostral ventrolateral medulla (RVLM) have been implicated in stress-induced hypertension (SIH). Prorenin, a member of the brain renin-angiotensin system (RAS), can directly activate microglia. The present study aimed to investigate the effects of prorenin on microglial activation in the RVLM of SIH rats. Rats were subjected to intermittent electric foot-shocks plus noise, this stress was administered for 2 h twice daily for 15 consecutive days, and mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were monitored. The results showed that MAP and RSNA were augmented, and this paralleled increased pro-inflammatory phenotype (M1) switching. Prorenin and its receptor (PRR) expression and the NLR family pyrin domain containing 3 (NLRP3) activation were increased in RVLM of SIH rats. In addition, PLX5622 (a microglial depletion agent), MCC950 (a NLRP3 inhibitor), and/or PRO20 (a (Pro)renin receptor antagonist) had antihypertensive effects in the rats. The NLRP3 expression in the RVLM was decreased in SIH rats treated with PLX5622. Mito-tracker staining showed translocation of NLRP3 from mitochondria to the cytoplasm in prorenin-stimulated microglia. Prorenin increased the ROS-triggering M1 phenotype-switching and NLRP3 activation, while MCC950 decreased the M1 polarization. In conclusion, upregulated prorenin in the RVLM may be involved in the pathogenesis of SIH, mediated by activation of the microglia-derived NLRP3 inflammasome. The link between prorenin and NLRP3 in microglia provides insights for the treatment of stress-related hypertension.
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Objective To explore the best operation method in the patients with papillary thyroid microcarcinoma.Methods A total of 139 patients with papillary thjroid microcarcinoma were treated at our institute between Jan.2000 and Jan.2010.The data on the clinicopathological characteristics of patients and treatment were collected.Results The mean tumor size was (0.45 ± 0.24) cm.Of the 139 patients,30.2％ had multifocal tumors,19.4％ had bilateral tumors,42.4％ neck lymph node metastases.The number of eases of lymph node metastasis in level Ⅵ,Ⅱa,Ⅲ and Ⅳ was 58(41.7％),3(2.2％),10(7.9％),5(3.6％),respectively.Only one had lymph node metastasis in Level Ⅲ Microscopic extrathyroid extension was associated with neck lymph node metastases in papillary thyroid microcareinoma patients (x2 =38.39,P ＜0.001).No one developed permanent hypoparathyroidism.The median follow-up time was 103 (range,30-154) months,and local recurrence in the thyoid was diagnosed in 2 patients who underwent hemi-or subtotal thyroidectomy.Follow-up of 10 years was done in 16 cases,and the survival rate of 139 patients for 10-year was 100％.Conclusions It suggested that patients with papillary thyroid microcarcinoma has uniform clinicopathologic characteristics and the pattern of lymph node metastasis from those with papillary thyroid carcinoma.Total thyroidectomy plus level Ⅵ dissection is the optimal surgical treatment of papillary thyroid microcarcinoma.
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Objective To explore the pattern of cervical nodal metastasis and the clinical significance of total thyroidectomy plus functional neck lymphadenectomy in papillary thyroid carcinoma patients. Methods Clinical and pathological data of 172 patients with papillary thyroid cancer who underwent total thyroidectomy plus functional neck lymph node dissection at Jinan Military General Hospital were retrospectively reviewed, including patient demographics, extent of surgery, parathyroid hormone level,recurrence, tumor pathology, such as tumor size, multifocality, capsular invasion, vascular invasion,extrathyroidal extension, and lymph node status. Results Of the 172 functional neck dissection patients (47 ambilateral), the incidence of lymphonodus metastasis in regions Ⅵ, Ⅳ and Ⅲ was 96. 3% ,78. 5%and 62.1% respectively. Rate of nodal metastasis was higher in patients with extracapsular invasion than in patients with no invasion ( P ＜ 0. 05 ). Serum parathyroid hormone levels significantly decreased immediately postoperatively in total thyroidectomy plus functional neck dissection and remained low for several weeks thereafter ( P ＜ 0. 01 ). The 5-, 10- and 15-year survival rate was ( 98. 83 ± 0. 82) %, (98. 23 ± 1.02 ) % and (96. 42 ± 1.43 )%, respectively. Conclusions Therapeutic neck lymph node dissection for papillary thyroid cancer is recommended for cervical nodal metastasis patients. Total thyroidectomy plus functional neck dissection is important in the treatment of papillary thyroid cancer.
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The purpose of this study was to evaluate the effect and mechanism of naloxone(NAL)in the treatment of traumatic shock. A traumatic shock animal model in Sprague-Dawley rats was reproduced, and the animals were randomly divided into two groups with respect to treatment or non-treatment with NAL. Plasma ?-endorphin(?-EP), nitric oxide(NO)and endothelin(ET) levels and oxygen partial pressure in tissues, including skeletal muscles, liver and small intestine, were determined before trauma,after traumatic shock, and 1h, 3h, and 5h after resuscitation. Meanwhile, hemodynamic parameters of the rats and their survival rates at 12h and 24h were monitored and recorded. The data showed that changes in plasma ?-EP, NO, ET levels and oxygen partial pressure in tissues of the two groups were statiscally significantly different between pre-trauma and post-shock periods(P
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The purpose of this study was to evaluate the dynamic changes in nitric oxide(NO), endothelin(ET) and oxygen partial pressure in tissues in the pathogenesis of traumatic shock, and to explore the therapeutic effect of L-Arginine. Traumatic shock was produced in Sprague-Daulay rats, and they were randomly divided into shock group and treatment group. NO and ET were assayed in blood, muscles, liver and small intestine before and after shock. Meanwhile, hemodynamic data of the rats and their survival time were monitored and recorded. The data showed that plasma NO and ET levels were elevated significantly after traumatic shock. There was statistical significance in tissues oxygen partial pressure between pretrauma and postshock periods. Plasma ET levels of treatment group at 5,12h after resuscitation were significant lower than that of shock group, and NO/ET were higher after resuscitation than that of shock group. Oxygen partial pressure in the liver and small intestine of treatment group were significant higher after resuscitation than that of shock group, and their survival rates at 12,24h were higher than that of shock group(P
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The incidence rate of trauma has been on the rise in recent years,and traumatic shock remains one of the main pathological conditions which endangers human life worldwide. This review covers the fundamental studies of trauma, multiple organ dysfunction after traumatic shock, the significance of cytokines in shock, the present strategies and advancements in treatment progress of shock. In addition, a prospect of the study of traumatic shock is discussed
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To study the role of endothelin(ET) in the pathogenesis of traumatic shock. Multiple injuries involving the leg bones, the soft tissue and hemorrhage in Sprague Daulay rat were produced by smashing its legs on both sides to induce traumatic shock. Dynamic changes in plasma ET, arterial blood gas analysis (ABGA) and oxygen partial pressure in tissues including skeletal muscles,liver and small intestine were detected at pre trauma and post shock periods. Meanwhile, hemodynamic parametars of the rats and their survival time were monitored and recorded. The data showed that plasma ET levels increased significantly after traumatic shock, reaching a peak of about 2 5 times of normal levels. There was statistically significant difference of ABGA values and tissues oxygen partial pressure between pre trauma and post shock periods. Metabolic acidosis appeared during traumatic shock. The changes in oxygen partial pressure in liver and small intestine were more significant than that of skeletal muscles. The data suggested that the significant increase in plasma ET contents after traumatic shock, might plays an important role in maintaining the blood pressure in the earty stage of shock, but might be an important cause of death in the late stage. The irreversible decrease in oxygen partial pressure in internal organs might be the key factor of refractoriness to resuscitation in an late stage of shock
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The aim of this study was to investigate the significance of low blood pressure (permissive hypotension) resuscitation in the treatment of uncontrolled traumatic shock. A traumatic shock animal model was replicated in Sprague Dawlay rats, the animals were randomly devided into non resuscitation group, traditional resuscitation group and low blood pressure resuscitation group. Prothrombin time(PT), activated pactial thromboplastin time(APTT) and oxygen partial pressure in tissues, including skeletal muscles, liver and small intestine, were determined before and after shock. Meanwhile, hemodynamic parameters of the rats and their survival time were monitored and recorded. The data showed that there were statistically significante difference in PT, APTT and amount of blood loss during shock between traditional resuscitation group and the other two groups. Low blood pressure (permissive hypotension) resuscitation could significantly improve oxygen partial pressure in tissues and prolong the mean survival time. The data suggested that low blood pressure resuscitation was a more rational strategy to improve the prognosis in rats with uncontrolled traumatic shock than traditional resuscitation strategy.
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To study the dynamic changes and the significance of oxygen partial pressure in tissues in rats with traumatic shock, a traumatic shock model in Sprague Dawley rats were reproduced by limbs wounding, and oxygen partial pressure in tissues, including skeletal muscles,liver and small intestine, were assayed before trauma and after shock based on oxygen dependent quenching. Meanwhile, hemodynamic parameters of the rats were monitored. The results showed that oxygen partial pressure in tissues decreased significantly after traumatic shock( P
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To establish a standard experimental model of traumatic shock in rats that could not only imitate clinical features,but also be performed easily, multiple injuries involving the leg bones,the soft tissue and hemorrhage in Sprague Daulay rats were made by hitting its legs on both sides with a 2500g pontil falling from 30cm height to induce traumatic shock. Resuscitated the rats after 90 minutes and monitored the vital signs,and then calculated the 24 hour and 72 hour death rates. There were about (7 8?1 6) minutes of the rats from injury to shock. The death rates were 27 5% in 24 hours and 52 5% in 72 hours. This model has been proved to be relatively simple,stable and basically closed to clinical features of traumatic shock, so it is a reliable,acute animal model for experimental study of traumatic shock.
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Objective To investigate the effect of nitric oxide synthase(NOS) inhibitors and L-arginine(L-Arg) on the prognosis of traumatic shock in rats. Methods Traumatic shock models of Sprague-Daulay rats were made and randomly devided into control group (n=24),L-NAME treatment group (n=24),AG treatment group (n=24) and L-Arg treatment group (n=24). Serum nitric oxide(NO) levels and oxygen partial pressure in tissues include skeletal muscles,liver and small intestine were detected at 1h,3h,5h after resuscitation. Meanwhile, hemodynamic data of the rats and their survival rates of 12h and 24h were monitored and recorded. Results Serum NO concentration was statistically lower after resuscitation in L-NAME group than that in control group, while there were no statistical significance of tissues oxygen partial pressure and survival rate in 12、24h between the two groups. AG could decrease serum NO levels only at late stage of traumatic shock,but no effect on the synthesis and relase of NO at early stage of traumati shock.AG could improve tissues oxygen partial pressure of the liver and small intestine, and prolonged the mean survival time. L-Arg could increase serum NO levels, and improve oxygen partial pressure of intestine and significantly increase the survival rate at 12h and 24h in rats with traumatic shock. Conclusions Treatment with AG and L-Arg can improve the prognosis of traumatic shock rats much better than that with L-NAME.