肿瘤坏死因子α与白细胞介素6在糖尿病大鼠骨骼肌中表达的实验研究

目的 探讨糖尿病大鼠骨骼肌中炎性细胞因子肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6的表达及其与细胞凋亡的关系.方法 将Wistar大鼠16只分为实验组和对照组各8只.实验组饲以8周高脂高糖饮食后腹腔内注射小剂量链脲佐菌素(30 mg/kg).对照组仅注射柠檬酸-柠檬酸钠缓冲液.第13周末处死大鼠.观察TNF-α及IL-6的蛋白表达,检测骨骼肌细胞中caspase 3的表达,并计算二者的相关性.结果 与对照组数据[TND-a、IL-6、caspase 3分别为(0.63±0.35)%、(2.05±0.83)%、(10.02±0.82)%]相比,实验组大鼠骨骼肌中TNF-α与IL-6(3.75±1.38%,5.77±0.74%)的表达水平均升高(P＜0.01),caspase 3[(10.02±0.82)%]表达明显高于(P＜0.01),TNF-α、IL-6与caspase3的表达具有相关性(r=0.713,r=0.692,P＜0.05).结论 糖尿病骨骼肌病变时炎症与凋亡同时发生,并可能共同导致胰岛素抵抗.

Abstract：

Objective To evaluate changes of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)expression in quadriceps femoris muscle of diabetic and control rats, and to explore the corelation among TNF-α, IL-6 and caspase 3. Methods Totally 16 adult (aged 8 weeks) Wistar rats were divided into non-diahetic (n =8)group and diabetic (n = 8) group. Diabetic rats were fed by high lipid and glucose diet. After 8 weeks, they were made by a single injection of streptozotocin (STZ) at a dose of 30 mg/kg and control rats were injected by citrate buffer ( pH 4.5 ) in the same dose. Quantitative immunohistochemistry assay for TNF-α, IL-6 and caspase 3 was applied. The quantitative analysis was used to evaluate the positive rate of TNF-α, IL-6 and caspase 3 expression and correlation analysis was used to evaluate the corelation of them. Results TNF-α, IL-6 protein had higher expression (3.75 ± 1.38,5.77 ± 0.74) in quadriceps femoris muscle of diabetic rats than those in controls (P ＜ 0.01 ).Caspase 3 ( 10.02 ±0.82) had higher expression in muscle of diabetic rats than that in controls (P ＜0.01 ). There was significant correlation among TNF-α, IL-6 and caspase 3 (r=0. 713,r=0. 692,P ＜0.05). Conclusions In muscle of diabetic rats, apoptosis is closely related to TNF-α and IL-6 protein which may induce the insulin resistance.     

炎性细胞因子与心力衰竭的相关性研究

目的探讨肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）与慢性心力衰竭（CHF）的关系。方法采用放射免疫分析法（RIA）和酶联免疫吸附法（ELISA）测定血清TNF-α、IL-6、IL一10的含量。结果心功能Ⅳ级组患者血清TNF-α、IL-6、IL-10含量显著高于对照组和心功能Ⅱ、III级组（P〈0．05）,心功能Ⅲ级患者的TNF-α、IL-6、IL．10水平显著高于心功能Ⅱ级患者和对照组（P〈0．05）。CHF组血清TNF-α和IL-6水平与LVEF呈负相关（r=-0．755,-0．751）。CHF组血清IL-10水平与LVEF呈正相关（r=0．476）。结论TNF-α、IL-6、IL-10水平与CHF发生发展密切相关。     

炎性细胞因子与2型糖尿病骨质疏松症关系的研究

目的:初步探讨2型糖尿病骨质疏松症与急性时相血清淀粉样蛋白A等相关危险因素之间的关系.方法:以100例男性2型糖尿病患者为研究对象.按腰椎骨密度(BMD)分为骨量正常组(A组)63例、低骨量组(B组)21例和骨质疏松组(C组)16例;比较3组间患者的年龄、体质量指数(BMI)、病程、血糖(FBG)、糖化血红蛋白(HbA1c)、血脂、急性时相血清淀粉样蛋白A(A-SAA)、尿白蛋白排泄率(UAER)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6等指标之间的差异,并进行相关性分析.结果:3组间的年龄、BMI、病程、HbA1c、FBG、A-SAA、UAER、TNF-α、IL-6差异均有统计学意义(P＜0.05).BMD与年龄、FBG、病程、HbA1c、A-SAA、UAER、TNF-α、IL-6呈负相关(P＜0.05),与BMI呈正相关(P＜0.05).结论:高血糖及A-SAA、TNF-α和IL-6水平的增高与2型糖尿病骨质疏松症的发生相关.     

糖尿病酮症酸中毒患者血清中炎性细胞因子水平增高的临床意义

目的探讨糖尿病酮症酸中毒患者血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)水平变化与病情加重的关系。方法选取46例糖尿病酮症酸中毒患者,其中合并感染者28例,非感染者18例,同时选取同期非酮症糖尿病患者32例作为对照组。留取清晨空腹静脉血,检查血常规同时检测各组患者空腹血糖(FPG)、糖化血红蛋白(Hb A1c)生化指标的变化情况;收集患者尿液检测尿酮体变化;ELISA法检测血清IL-6,TNF-α,CRP水平。结果 DKA感染组和非感染组血清IL-6、TNF-α、CRP水平均明显高于对照组,差异具有统计学意义(均P<0.05)。与DKA非感染组相比,DKA感染组IL-6、TNF-α、CRP水平也有明显升高,差异也具有统计学意义(P<0.05)。DKA合并感染患者空腹血糖与IL-6、TNF-α、CRP均成正相关(r分别为0.534、0.652、0.493,均P<0.01),而DKA合并感染患者CRP与IL-6、TNF-α亦成正相关(r分别为0.678、0.624,均P<0.01)。结论糖尿病酮症酸中毒患者的血清IL-6、TNF-α、CRP水平变化明显升高,与疾病严重程度有一定的关系。     

实验性糖尿病大鼠血清一氧化氮与细胞因子的相关性研究

为观察实验性糖尿病大鼠血清一氧化氮与细胞因子的相关性 ,采用链脲佐菌素复制糖尿病动物模型 ,用比色法测定其血清一氧化氮 (nitric oxide,NO)含量和一氧化氮合成酶 (NO synthetase,NOS)活力 ,用放免法测定其血清中肿瘤坏死因子 (tumornecrosis factor,TNFα)和白细胞介素 -6 (Inter leukin-6 ,IL-6 )。结果显示 ,在实验性糖尿病大鼠血清中 NO与 TNFα和 IL -6均呈高度正相关 ,并且随病程延长 NO与 TNFα含量逐渐增加。     

实验性糖尿病大鼠血清细胞因子与肾功能不全的相关性研究

为探讨实验性糖尿病大鼠血清细胞因子与肾功能不全的相关性 ,用链脲佐菌素 (streptozotocin ,STZ)复制糖尿病动物模型 ,用放射免疫分析法测定血清肿瘤坏死因子 (tumornecrsisfactor,TNF α)和白细胞介素 6(interleukin 6 ,IL 6)含量 ,用比色法测定血清肌酐 (creatinine ,Cr)和尿素氮 (bloodureanitrogen ,BUN)含量。结果表明 ,实验性糖尿病大鼠血清TNF α与Cr和BUN的含量随病程进行性增加 ,TNF α和IL 6与Cr和BUN均明显正相关。     

癫痫患者的血清细胞因子水平变化及其临床意义

目的探讨白细胞介素-2（IL-2）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）对癫痫患者的神经免疫调节作用。方法采用双抗体夹心酶联免疫吸附试验（ELISA）检测45例癫痫患者血清中IL-2、IL-6和TNF-α的水平,并与年龄和性别相匹配的40例正常对照组进行比较。结果癫痫组血清IL-2、IL-6和TNF-α的水平均明显高于对照组（P〈0.01）。相关分析发现癫痫患者血清IL-2、IL-6与TNF-α水平之间呈显著正相关（r=0.49,P〈0.01;r=0.56,P〈0.01）。结论癫痫患者的免疫系统处于活化状态,细胞因子水平的失衡参与了癫痫的免疫病理过程。     

板蓝根对脂多糖刺激鼠释放炎性细胞因子的影响

目的探讨板蓝根抗内毒素活性部位F022对脂多糖(LPS)刺激鼠单核细胞释放炎性细胞因子的影响。方法取BALB/C小鼠腹腔内单核细胞,实验设计为6组。其中,实验组根据F022浓度分为1%、0.5%、0.25%、0.125%4组,分别加入板蓝根F022部位液后再加入LPS液;LPS阳性组仅加入LPS液;阴性组加入1%F022液。之后检测细胞培养上清液中3种炎性细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)和一氧化氮(NO)水平。结果LPS可刺激鼠单核细胞过度释放炎性细胞因子TNF-α、IL-6和NO;与阳性组比较,实验组炎性细胞因子水平降低,且呈剂量依赖性。结论板蓝根抗内毒素活性部位F022对LPS刺激鼠单核细胞过度释放炎性细胞因子具有抑制作用。     

静脉血栓栓塞症与炎性细胞因子

静脉血栓栓塞症(VTE)包括深静脉血栓形成(DVT)及肺血栓栓塞症(PTE)两种临床表现形式，是临床常见疾病，致残率和病死率高。目前其发病机制尚不明确，研究认为VTE较明确的危险因素有制动、创伤、外科手术、恶性肿瘤、以及活化蛋白C抵抗、抗凝血蛋白C、蛋白S缺乏等遗传性病变。随着炎症反应与血栓形成的作用机制及炎症反应在动脉血栓性疾病中临床研究的深入，     

子痫前期患者胎盘组织中促炎与抗炎细胞因子mRNA的表达及意义

目的 探讨促炎细胞因子与抗炎细胞因子mRNA在子痫前期患者胎盘组织中的表达及意义.方法 采用RT-PCR技术测定36例正常足月妊娠妇女(A组)和24例轻度子痫前期患者(B组)及17例重度子痫前期患者(C组)胎盘组织中肿瘤坏死因子(TNF-α、白细胞介素(IL)-1、IL-4、IL-6、IL-10 mRNA的表达水平.结果 C组TNF-α、IL-6、IL-1 mRNA表达水平分别为(1.81±0.23)、(1.31±0.19)和(0.99±0.16),显著高于B组的(0.98±0.18)、(1.07±0.15)和(0.61±0.12)及A组的(0.92±0.14)、(0.72±0.11)和(0.65±0.11)(P<0.05).C组IL-4、IL-10 mRNA表达水平分别为(0.38±0.09)和(0.25±0.15),显著低于B组的(0.59±0.16)和(0.83±0.20)及A组的(0.81±0.13)和(0.94±0.25)(P<0.05).B组IL-6 mRNA表达水平显著高于A组(P<0.05);B组IL-4 mRNA表达水平显著低于A组(P<0.05).结论 子痫前期患者胎盘组织中促炎细胞因子TNF-α、IL-1、IL-6 mRNA表达水平上调,抗炎细胞因子IL-4、IL-10 mRNA表达水平降低.     

糖尿病患者血清肿瘤坏死因子C反应蛋白水平改变及其与牙周病的关系

目的检测2型糖尿病合并牙周病患者血中炎性标志物C反应蛋白(CRP)和肿瘤坏死因子(TNF)-α水平的变化,探讨二者与糖尿病牙周病的关系。方法对584例2型糖尿病患者进行牙周病的筛查,检测血CRP、TNF-α与健康体检配对人群进行相关指标比较。结果2型糖尿病牙周病的患病率高达63.7%,对照组为21.6%。糖尿病合并牙周病患者CRP为(8.4±0.9)mg/L,糖尿病无牙周病患者为(5.9±0.8)mg/L,两者差异有统计学意义(P<0.01)。TNF-α在糖尿病合并牙周病组为(234±28)ng/L,明显较糖尿病无牙周病组的[(178±28)ng/L]增高(P<0.01)。结论糖尿病与牙周病两者互相影响,相互促进,导致牙周病加重及糖尿病大血管并发症进展。     

Therapeutic implications of endothelin and thrombin G‐protein‐coupled receptor transactivation of tyrosine and serine/threonine kinase cell surface receptors

Objectives This review discusses the latest developments in G protein coupled receptor (GPCR) signalling related to the transactivation of cell surface protein kinase receptors and the therapeutic implications. Key findings Multiple GPCRs have been known to transactivate protein tyrosine kinase receptors for almost two decades. More recently it has been discovered that GPCRs can also transactivate protein serine/threonine kinase receptors such as that for transforming growth factor (TGF)‐β. Using the model of proteoglycan synthesis and glycosaminoglycan elongation in human vascular smooth muscle cells which is a component of an in vitro model of atherosclerosis, the dual tyrosine and serine/threonine kinase receptor transactivation pathways appear to account for all of the response to the agonists, endothelin and thrombin. Summary The broadening of the paradigm of GPCR receptor transactivation explains the broad range of activities of these receptors and also the efficacy of GPCR antagonists in cardiovascular therapeutics. Deciphering the mechanisms of transactivation with the aim of identifying a common therapeutic target remains the next challenge.     

过敏性紫癜患儿血清IL-8、IL-12及TNF-α表达的意义

目的探讨血清白细胞介素-8（IL-8）、白细胞介素-12（IL-12）及肿瘤坏死因子-α（TNF-α）在过敏性紫癜（HSP）患儿中表达及其临床意义。方法对本研究采用ELISA方法检测了48例过敏性紫癜患儿（其中22例合并肾脏损害）以及30例正常健康儿童的血清IL-8、IL-12及TNF-α水平，分别比较急性期和缓解期以及有无合并肾损害的过敏性紫癜患儿的细胞因子水平；分析IL-8、IL-12与TNF-α是否存在相关关系。结果HSP患儿血清IL-8、IL-12与TNF-α水平高于健康对照组（P〈0．01）；无肾损害HSP与紫癜性肾炎（HSPN）组血清IL培、IL-12水平均无统计学差异；HSPN组肿瘤坏死因子-α水平高于无肾损害HSP组；HSP血清TNF-α水平与IL-8正相关（r=0．524P〈0．01）。HSP患儿血清TNF-α水平与IL-12正相关（r=0．670，P〈0．01）。结论细胞因子IL-8、IL-12及TNF-α可能参与HSP／HSPN发病过程。     

血清同型半胱氨酸胱抑素维生素B6及炎症因子在糖尿病肾脏病中的临床意义

目的 探讨血清同型半胱氨酸（Hcy）、胱抑素C（Cys-C）、维生素B6（Vit B6）、白介素6（IL-6）、肿瘤坏死因子α（TNF-α）与糖尿病肾脏病（DKD）的相关性,分析DKD的相关危险因素。方法 收集2015年3月至2016年1月皖北煤电集团总医院肾内科及内分泌科收治的2型糖尿病患者80例,根据24 h尿白蛋白排泄率分为非DKD组（19例）和DKD组（61例）。酶联免疫吸附法统一检测血清IL-6、TNF-α、Vit B6水平。受试者工作特征曲线（ROC）分析Cys-C对DKD的诊断价值,Spearman相关分析检验各指标与DKD患者Cys-C和Hcy的相关性,DKD患者的Hcy和Cys-C相关分析采用多元线性回归分析。结果 Cys-C的ROC曲线下面积为0.77（P<0.05）,灵敏度为57.38%,特异度为84.21%,尿酸（SUA）、24 h尿白蛋白与DKD患者的Cys-C水平呈正相关（r_s=0.531、0.515,P<0.05）,Vit B6、SUA与DKD患者Hcy水平呈正相关（r_s=0.342、0.289,P<0.05）。多元线性回归分析显示,SUA、24 h尿白蛋白、Hcy与Cys-C呈正相关性（P<0.05）。结论 Cys-C对DKD有诊断价值,SUA、尿白蛋白、Hcy参与DKD发生发展,Vit B6通过降低Hcy对DKD起到保护作用。     

老年糖尿病肾病与炎性因子的关系

目的探讨老年糖尿病肾病与炎症因子的关系。方法选择老年科门诊及住院的老年2型糖尿病患者96例,根据尿白蛋白排泄率分为3组：正常蛋白尿组19例,UAER〈20μg／min;微量蛋白尿组,UAER20～200μg／min;临床蛋白尿组,UAER〉200μg／min。抽取空腹静脉血,分别测定3组患者血清TNF—α、IL-6、C-RP的含量,用放射免疫分析测定血清肿瘤坏死因子、白介素-6（IL-6）的含量,用透射比浊法测定C反应蛋白（RP）。结果3组血清TNF-α、IL-6、CRP的含量有显著差异（P〈0．05）,微量蛋白尿组和临床蛋白尿组的血清TNF-α、IL-6、CRP的含量明显高于正常蛋白尿组（P〈0．05）,并随着糖尿病肾病程度的加重而逐步升高。结论炎性反应可能参与了糖尿病肾病的发生发展,对炎性因子的监测有益于老年糖尿病肾病的诊治。     

Effect of verapamil on cardiac protein kinase C activity in diabetic rats

We examined the effect of verapamil treatment on cardiac protein kinase C (PKC) activity in streptozocin-induced diabetic rats. Basal cardiac PKC activity in diabetes increased in both cytosolic (by 94%, P < 0.01) and membrane (by 41%, P < 0.05) fractions as compared with that in controls. Subcutaneous administration of 8 mg/kg verapamil twice a day for 8 weeks induced a significant decrease in both cytosolic (by 59%, P < 0.01) and membrane (by 50%, P < 0.01) PKC activity in diabetes as compared with the activity in the non-treated diabetic groups. In contrast, cardiac cytosolic PKC activity in control rats was significantly (P < 0.01) decreased by 41% as compared with that of the non-treated control group without there being any change in membrane PKC activity. Our data demonstrate that verapamil treatment may ameliorate the abnormal activation of cardiac PKC in diabetes.     

细胞因子TNF-α、IL-6与老年高血压患者合并颈动脉粥样硬化的关系

目的:探讨细胞因子TNF-α、IL-6与老年高血压患者颈动脉粥样硬化发生之间的关系。方法:选择142例老年高血压患者,男104例、女38例,平均年龄(75.63±3.93)岁,应用颈动脉超声测量颈动脉内中膜厚度(IMT),观察有无斑块形成,用免疫学方法测定血清中TNF-α、IL-6的浓度。结果:合并颈动脉粥样硬化的老年高血压患者血清TNF-α、IL-6的含量明显高于无颈动脉硬化患者(P<0.05=;有颈动脉斑块的患者血清TNF-α、IL-6的含量明显高于颈动脉内中膜增厚及内中膜正常患者(P<0.05,P<0.01)。结论:细胞因子TNF-α、IL-6参与高血压患者颈动脉粥样硬化的发生发展过程。     

Tanshinone IIA suppresses lung injury and apoptosis, and modulates protein kinase B and extracellular signal-regulated protein kinase pathways in rats challenged with seawater exposure

1. Tanshinone IIA (TIIA) is one of the main active components of the Chinese herb, Danshen. In the present study, we investigated the role of apoptosis in seawater exposure-induced acute lung injury (ALI), and explored the effects of TIIA on lung injury, apoptosis, and protein kinase B (Akt) and extracellular signal-regulated protein kinase (ERK) pathways in seawater-challenged rats. The rats were randomly divided into four groups: (i) naive group, no drug was given; (ii) TIIA control group, TIIA (50 mg/kg) was given intraperitoneally; (iii) seawater (SW) group, seawater (4 mL/kg) was given; and (iv) TIIA/SW group, TIIA (50 mg/kg) was injected intraperitoneally 10 min after seawater instillation. 2. The results showed that TIIA treatment significantly improved seawater exposure-induced lung histopathological changes, alleviated the decrease in PaO(2) , and reduced lung oedema, vascular leakage and cell infiltration. As shown by terminal deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) assay, seawater exposure induced apoptosis in lung tissue cells. Furthermore, seawater exposure also changed apoptosis-related factors Bcl-2 and caspase-3, and caused a reduction in the activation of Akt and ERK1/2 pathways. Furthermore, TIIA treatment decreased the number of apoptotic cells, reversed changes in Bcl-2 and caspase-3, and upregulated the activation of Akt and ERK1/2 in seawater-challenged rats. 3. In conclusion, the data suggest that apoptosis might play an important role in seawater exposure-induced lung injury and that TIIA could significantly attenuate the severity of ALI and apoptosis in seawater-challenged rats, which is possibly through modulation of Akt and ERK1/2 pathways.     

茯苓多糖对2型糖尿病大鼠丝裂原激活的蛋白激酶通路及胰岛素抵抗的影响

目的 探究茯苓多糖(PAC)对2型糖尿病(T2DM)大鼠丝裂原激活的蛋白激酶(MAPK)通路及胰岛素抵抗(IR)的影响。方法 2019年3—10月,采用高脂高糖喂养联合腹腔注射链脲佐菌素(STZ)建立T2DM大鼠模型,采用随机数字表法分为模型(T2DM)组、二甲双胍(MET)组(0.65 g·kg^-1·d^-1)和PAC低(PAC-L,0.05 g·kg^-1·d^-1)、中(PAC-M,0.10 g·kg^-1·d^-1)、高剂量(PAC-H,0.20 g·kg^-1·d^-1)组,每组12只。另取12只正常非T2DM大鼠为正常组(NC组),干预8周后测定空腹血糖、空腹血清胰岛素(FINS)、三酰甘油及肝组织均浆丙二醛、谷胱甘肽过氧化物酶(GSH-Px)和超氧化物歧化酶(SOD)活性,采用蛋白质印迹法检测肝脏组织磷酸化p38丝裂原激活的蛋白激酶(p-p38MAPK)、磷酸化c-Jun氨基末端激酶(p-JNK)蛋白表达水平。结...