金银花提取物对重症急性胰腺炎肺损伤大鼠的保护作用及机制研究

摘要 目的：探讨金银花提取物对重症急性胰腺炎肺损伤大鼠的保护作用及其分子机制。方法：选择60只大鼠并将其分为假手术组、模型组、金银花低剂量组、金银花中剂量组和金银花高剂量组。比较各组的肺组织和胰腺组织病理评分。采用全自动血气分析仪检测各组大鼠血氧分压、二氧化碳分压和氧合指数。采用酶联免疫吸附法检测各组炎症因子[白细胞介素（IL）-1、IL-6和肿瘤坏死因子-α（TNF-α）]水平。免疫印迹法检测各组肺组织中NF-κB通路相关蛋白（p-p65、p-IκBα、p65和IκBα蛋白）水平。结果：与假手术组相比,模型组肺组织和胰腺组织病理评分以及二氧化碳分压明显升高（P<0.05）。与模型组相比,金银花各剂量组肺组织和胰腺组织病理评分以及二氧化碳分压明显下降,并且呈剂量依赖性（P<0.05）。与假手术组相比,模型组血氧分压和氧合指数明显下降（P<0.05）。与模型组相比,金银花各剂量组血氧分压和氧合指数明显升高,并且呈剂量依赖性（P<0.05）。与假手术组相比,模型组IL-1、IL-6和TNF-α水平以及p-p65和p-IκBα蛋白水平明显升高（P<0.05）。与模型组相比,金银花各剂量组IL-1、IL-6和TNF-α水平以及p-p65和p-IκBα蛋白水平明显下降,并且呈剂量依赖性（P<0.05）。结论：金银花提取物对大鼠重症急性胰腺炎肺损伤具有一定保护作用,能够升高血氧分压和氧合指数并降低二氧化碳分压,并且其保护作用可能是通过抑制NF-κB通路介导的促炎症因子IL-1、IL-6和TNF-α的产生,缓解炎症性肺损伤。     

Aurora-A激酶对急性胰腺炎大鼠肺脏损伤的修复作用研究

摘要 目的：探讨与研究Aurora-A激酶对急性胰腺炎大鼠肺脏损伤的修复作用。方法：36只雄性SD大鼠均分为三组：对照组、模型组与Aurora-A组。对照组进行假手术操作,模型组建立急性胰腺炎模型后给予注射等量生理盐水治疗,Aurora-A组建立急性胰腺炎模型后给予阴茎背静脉注射鼠Aurora-A类因子-MLN8054 10 mg/kg治疗,记录大鼠肺脏损伤的修复情况。结果：造模过程中无大鼠死亡情况发生,模型组与Aurora-A组造模后2 w与4 w的肺组织病理评分、血清中性粒细胞弹性蛋白酶(neutrophil elastase,NE)与髓过氧化物酶(myeloperoxidase,MPO)含量、肺组织W/D、肺组织蛋白激酶B(AKT)、细胞外信号调节激酶1(ERK1)蛋白相对表达水平都高于对照组(P<0.05),Aurora-A组少于模型组(P<0.05)。结论：Aurora-A激酶在急性胰腺炎大鼠的应用能抑制Akt/ERK信号通路激活,减少血清NE与MPO的表达,从而促进肺脏损伤修复。     

肠内营养联合微生态制剂对重症胰腺炎患者的疗效

目的观察肠内营养联合微生态制剂对重症胰腺炎患者细菌移位、免疫功能、炎症反应的影响。方法选择我院2017年1月至2019年7月收治的200例重症胰腺炎患者为研究对象,根据治疗方法不同分为A组、B组、C组。A组患者采用肠外营养治疗,B组患者采用肠内营养治疗,C组患者采用肠内营养联合微生态制剂治疗。比较3组患者的治疗效果,治疗后细菌移位情况、细胞免疫功能及炎症因子水平。结果 C组患者总有效率高于A组和B组(χ~2=5.423、9.629,P=0.020、0.002),A组和B组总有效率差异无统计学意义(χ~2=0.790,P=0.374)。治疗后,C组患者血清内毒素、D-乳酸水平低于A组和B组,同时B组低于A组(均P0.05)。治疗后,C组患者CD3~+细胞、CD4~+细胞、CD4~+/CD8~+水平高于A组和B组,同时B组高于A组(均P0.05)。C组患者CD8~+细胞水平低于A组和B组,同时B组低于A组(均P0.05)。治疗后,C组患者血清IL-6、IL-8、TNF-α水平低于A组和B组,同时B组低于A组(均P0.05)。结论肠内营养联合微生态制剂可改善重症胰腺炎患者细菌移位情况和免疫功能,减轻患者炎症因子水平。     

CXCL8 in thyroid disease: From basic notions to potential applications in clinical practice

CXCL8 was the first chemokine shown to be secreted by thyrocytes. Experimental data suggest that CXCL8 plays a role in thyroid homeostasis but its role in thyroid diseases remains poorly investigated. Clinical studies measuring the serum levels of CXCL8 in patients with autoimmune-thyroid-diseases reported conflicting results. Solid evidences support a role of CXCL8 as a tumor-promoting agent in several human cancers. Studies in thyroid cancer are still in their initial stage, but promising. Several evidences indicate that thyroid cancer may share with other human malignancies some of the effects of CXCL8 and highlight the possibility of using CXCL8 as a marker of aggressiveness. Basic and clinical evidences in favor or against a role for CXCL8 in thyroid diseases are discussed.     

Paraoxonase and arylesterase levels in autoimmune thyroid diseases

Objective: The aim of this study was to evaluate serum paraoxonase-1 (PON1) activity and its association with oxidative stress in autoimmune thyroid disease (AITD).

Methods: A total of 50 patients with AITD, including 25 with Hashimoto's thyroiditis and 25 with Graves’ disease were enrolled. The control group comprised 27 healthy subjects. Blood samples were obtained in the euthyroid period and 3 months after initiation of medical treatment. Serum samples from patients with AITD and the healthy control group were analyzed for basal PON1, salt-stimulated PON1, and arylesterase (ARE) activities, along with lipid hydroperoxide (LOOH) and total free sulfhydryl (–SH) levels.

Results: Serum PON1 activities and –SH levels were significantly lower (P?<?0.001, for each), whereas LOOH levels were significantly higher (P?<?0.001, for each) in patients with AITD, compared to the control group. We observed no significant differences in ARE levels between the patient and healthy control groups (P?>?0.05). PON1 activity was positively correlated with –SH (r?=?0.522, P?<?0.001) and negatively correlated with LOOH (r?=??0.487, P?<?0.001). PON1 phenotype distribution of the subjects was not significantly different among the three groups (P?=?0.961).

Conclusions: Serum PON1 activity is decreased in patients with AITD, and correlated positively with –SH, a well-known antioxidant, and negatively with LOOH, an index of lipid oxidation.     

Oxidative stress and antioxidant status in patients with autoimmune liver diseases

Abstract

Objective

To estimate oxidative stress and antioxidant components during different stages of autoimmune liver diseases and assess their possible implication on disease progression.

Methods

We determined several markers of oxidative injury (isoprostane, aldehydes, protein carbonyls, 3-nitrotyrosine, and myeloperoxidase) and antioxidant components (glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase) in whole blood, serum, and urine in 49 patients with autoimmune cholestatic liver diseases (AC) and 36 patients with autoimmune hepatitis (AIH) and healthy subjects matched for sex and age.

Results

Both AC and AIH patients had increased levels of all lipid and protein oxidative injury products and significantly decreased whole blood glutathione levels compared to controls. AIH patients had significantly higher levels of aldehydes and glutathione peroxidase activity and significantly lower protein carbonyl levels compared to AC patients. Protein carbonyl and isoprostane levels increased and glutathione levels decreased gradually with progression from mild fibrosis to severe fibrosis and cirrhosis in both AC and AIH patients. In addition, both cirrhotic AC and AIH patients had significantly higher protein carbonyls compared to non-cirrhotics.

Discussion

We provide novel findings in support of a major contribution of oxidant/antioxidant imbalance in the progression of liver injury in AC and AIH.     

早期肠内营养辅助治疗重症胰腺炎的临床疗效分析

目的：探讨早期肠内营养辅助治疗重症胰腺炎的临床效果。方法：选择2009年4月-2012年2月我院收治的重症胰腺炎患者共46例,随机分为实验组和对照组各23例,实验组在综合治疗的基础采用早期肠内营养治疗（EN）,而对照组在综合治疗的基础上采用全胃肠外营养治疗（TPN）,比较两组患者的血清总蛋白、白蛋白、尿素氮水平及血淋巴细胞百分比变化、血淀粉酶和尿淀粉酶恢复正常时间、住院时间及病死率,并比较两组治疗前及治疗后24、48及72小时的APACHEII评分。结果：治疗后,实验组患者的血清总蛋白、白蛋白、尿素氮水平及血淋巴细胞百分比变化均较对照组明显增高,差异有统计学意义（P〈0．05）,而血淀粉酶、尿淀粉酶恢复时间、病死率及住院时间分别均明显较对照组降低或缩短,差异有统计学意义（P〈0．05）。治疗24、48及72小时后,实验组APACHEII评分均较治疗前显著减低（P〈o．05）,而对照组治疗24、48h后APACHEⅡ评分与治疗前比较差异无统计学意义（P〉0．05）,治疗72h后APACHEII评分较治疗前显著减低（P〈O．05）。结论：采用早期肠内营养辅助治疗重症胰腺炎患者能有效保护肠黏膜屏障功能,改善患者的营养状况,增强患者的免疫力,并改善患者的预后。     

Interactions between enteroviruses and autophagy in vivo

Autophagy plays a protective role during many viral and bacterial infections. Predictably, evolution has led to several viruses developing mechanisms by which to evade the inhibitory effects of the pathway. However, one family of viruses, the picornaviruses, has gone one step further, by actively exploiting autophagy. Using mice in which Atg5 has been conditionally deleted in pancreatic acinar cells, we have studied the outcome of infection by coxsackievirus B3 (CVB3), a member of the enterovirus genus and picornavirus family. Two key findings emerged: disruption of autophagy (1) dramatically compromised virus replication in vivo, and (2) significantly limited pancreatic disease.     

VMP1 is a new player in the regulation of the autophagy-specific phosphatidylinositol 3-kinase complex activation

We have elucidated a novel mechanism through which the autophagy-specific class III phosphatidylinositol 3-kinase (PtdIns3K) complex can be recruited to the PAS in mammalian cells, through the interaction between BECN1 and the vacuole membrane protein 1 (VMP1), an integral autophagosomal membrane protein. This interaction involves the binding between the C-terminal 20 amino acids of the VMP1 hydrophilic domain, which we have named the VMP1 autophagy-related domain (VMP1-AtgD), and the BH3 domain of BECN1. The association between these two proteins allows the formation of the autophagy-specific PtdIns3K complex, which activity favors the generation of phosphatidylinositol-3-phosphate (PtdIns3P) and the subsequent association of the autophagy-related (ATG) proteins, including ATG16L1, with the phagophore membranes. Therefore, VMP1 regulates the PtdIns3K activity on the phagophore membrane through its interaction with BECN1. Our data provide a novel model describing one of the key steps in phagophore assembly site (PAS) formation and autophagy regulation, and positions VMP1 as a new interactor of the autophagy-specific PtdIns3K complex in mammalian cells.