缺硒大鼠心肌α_1受体、cAMP及儿茶酚胺含量的变化

实验用SD大鼠随机分为三组,分别用克山病区低硒粮饲料(Se 0.010ppm)、病区粮加亚硒酸钠饲料(Se 0.181ppm)及本院常规饲料喂养两月,处死动物,测定各项指标。结果发现,常规饲料组大鼠心肌与     

西藏大骨节病患者血清Se与几种细胞因子含量的变化

目的:测定大骨节病患者和正常对照血清中硒和肿瘤坏死因子-α(TNF-α)、血管内皮生长因子(VEGF)和白介素-1(IL-1β)的水平。从细胞因子角度为研究其发病机制提供实验依据。方法:在西藏拉萨尼木县和墨竹工卡县的大骨节病区随机选取大骨节病患者30例(患者组),病区正常人30例(病区内对照组),在拉萨非大骨节病区选健康志愿者30例(病区外对照组),3组人群年龄和性别没有显著性差异。采取静脉血离心制备血清。采用荧光法测定血清Se,酶联免疫吸附测定法(ELISA)检测血清中细胞因子水平。结果:西藏大骨节病病区患者和正常人血清中Se低于非大骨节病区正常人;患者血清中TNF-α、VEGF和IL-1β的水平高于正常。血清Se与TNF-α、IL-1β水平呈负相关趋势。结论:低硒和血清中细胞因子水平升高在KBD的发病过程中起着某种作用。     

虚拟病区对非内分泌科住院2型糖尿病患者的影响

目的:探讨"虚拟病区"对非内分泌科住院2型糖尿病(Diabetes mellitus type 2,T2DM)患者的影响.方法:选取我院2021年1月至2021年12月期间600例非内分泌科住院T2DM患者作为研究对象.按照计算机分组法分为对照组(299例)和观察组(301例).对照组给予传统血糖管理干预;观察组给予虚拟病区干预.观察两组血糖水平、血糖波动情况以及自我管理水平.结果:观察组糖化血红蛋白(Glycosylated hemoglobin,GHb)、空腹血糖(Fasting plasma glucose,FPG)、餐后两小时血糖(Blood sugar two hours after meal,2hPG)水平均低于对照组(P<0.05);出院时,观察组血糖均值(Mean blood sugar,MBG)、平均血糖波动幅度(Average blood sugar fluctuation range,MAGE)以及血糖标准差(Standard deviation of blood glucose,SDBG)均低于对照组(P<0.05);观察组自我管理水平各维度得分均高于对照组(P<0.05).结论:虚拟病区应用于非内分泌科住院T2DM患者调节患者自我管理能力,改善血糖波动情况,进而更好的控制血糖.     

恢复期精神分裂症加用帕罗西汀的社会功能研究

目的探讨利培酮加用小剂量的帕罗西汀对恢复期精神分裂症患者阴性症状、情绪表达、社会功能的影响。方法将71例恢复期精神分裂症患者随机分为干预组(36例)和对照组(35例)。对干预组给予利培酮加用帕罗西汀;对照组单用利陪酮。临床疗效采用阳性与阴性症状量表(PANSS)、个人和社会功能量表(PSP)作为评价指标。结果在加药后12周时,干预组的PANSS总分低于对照组(t=-5.801,P<0.001)。阳性量表分低于对照组(P<0.01);在PSP评分中,干预组的评分大于对照组评分(t=7.08,P<0.001)。组间比较,差异有显著性(P<0.01)。结论利培酮合用帕罗西汀可改善恢复期精神分裂症患者的情绪表达,减轻病耻感、焦虑情绪、增加生活动力,促进患者社会功能的恢复。     

奥贝胆酸对非酒精性脂肪肝大鼠法尼醇X受体及细胞色素P450家族成员7A1基因表达的影响

目的探讨奥贝胆酸对非酒精性脂肪肝(NAFLD)大鼠法尼醇X受体(FXR)蛋白、细胞色素P450家族成员7A1(CYP 7A1)蛋白及其基因表达的影响,及保肝作用。方法雄性SD大鼠52只通过高脂饲料喂养建立大鼠非酒精性脂肪肝模型;设置对照组11只,模型组、奥低组、奥中组和奥高组共41只,给药4周后,取大鼠相同部位肝脏,免疫组织化学法测定FXR蛋白表达、RT-PCR检测FXR mRNA,Western blotting法检测CYP 7A1蛋白、RTPCR检测CYP 7A1 mRNA的表达水平;通过大鼠肝指数,外周血谷丙转氨酶(ALT)、谷草转氨酶(AST)和碱性磷酸酶(ALP)的浓度,及肝脏组织切片观察,评估肝功能。结果高脂饲料喂养10周后,大鼠具有典型的NAFLD特征,模型建立成功。模型组的FXR蛋白和FXR mRNA表达水平显著低于对照组(P<0.05),奥低组和奥中组的FXR蛋白和FXR mRNA表达水平与模型组相比,差异无统计学意义(P>0.05),奥高组的FXR蛋白和FXR mRNA表达水平显著高于模型组(P<0.05);模型组、奥低组和奥中组的吸光度值显著低于对照组(P<0.05),奥高组显著升高,与对照组差异无统计学意义(P>0.05)。模型组的CYP 7A1蛋白和CYP 7A1 mRNA表达水平显著高于对照组(P<0.05),奥低组和奥中组的CYP 7A1蛋白和CYP 7A1 mRNA的表达水平与模型组相比,差异无统计学意义(P>0.05),奥高组的CYP 7A1蛋白和CYP 7A1 mRNA表达水平显著低于模型组(P<0.05)。与对照组相比,模型组的肝指数(%)显著增大(P<0.05);奥低组和奥中组的肝指数(%)与模型组相比,差异无统计学意义(P>0.05),奥高组肝指数(%)显著低于模型组(P<0.05)。与对照组相比,模型组的ALT、AST和ALP的浓度显著升高(P<0.05);奥贝胆酸组的ALT、AST和ALP浓度显著低于模型组(P<0.05),且随着奥贝胆酸给药量的增加,ALT、AST和ALP的浓度逐渐降低;肝组织切片观察结果显示,奥贝胆酸呈剂量依赖性改善大鼠肝组织。结论奥贝胆酸高剂量能显著上调FXR蛋白及其基因的表达,并抑制CYP 7A1蛋白及其基因的表达,显著改善大鼠肝功能及肝组织病理状态。     

多囊卵巢综合征患者脂联素和C一反应蛋白与颈动脉内膜中层厚度的关系

目的观察多囊卵巢综合征(PCOS)患者血清脂联素(APN)水平和C一反应蛋白(CRP)浓度与颈动脉内膜中层厚度(IMT)的关系,探讨PCOS患者是否存在早期动脉粥样硬化。方法选择我院PCOS患者51例作为研究对象,分为肥胖组与非肥胖组,同期选择非PCOS患者50例作为对照,测定血清APN水平和CRP浓度及内分泌代谢指标,同时采用彩色多普勒显像仪测量颈总动脉IMT。结果 PCOS肥胖组及非肥胖组血清APN水平低于对照组(P<0.05),CRP浓度、颈动脉IMT均明显高于对照组(P<0.05)。PCOS肥胖组血清APN水平低于非肥胖组(P<0.05);PCOS肥胖组血清CRP浓度、IMT高于非肥胖组,差异有统计学意义(P<0.05)。相关分析显示PCOS组APN与CRP,IMT、HOMA-IR均有显著的负相关(P<0.05或P<0.01)。CRP与IMT、HOMA-IR具有显著的正相关(P<0.05或P<0.01)。结论 PCOS患者尤其伴有肥胖者血清脂联素水平降低,CRP浓度升高,胰岛素抵抗增加,IMT增加,可能存在早期动脉粥样硬化。炎症反应可能参与了PCOS患者尤其伴有肥胖者早期动脉粥样硬化的发生发展。     

首发精神分裂症患者血浆非酶抗氧化物浓度与临床特征

目的:探讨在首发精神分裂症患者中血浆非酶抗氧化物浓度与临床特征的关系。方法:选择符合国际疾病分类第十版(ICD-10)的精神分裂症诊断标准首发患者64例,作为病例组(包括家族史阳性30例,阴性34例)和42名健康成人作为对照组,分别测定血浆白蛋白、总胆红素和尿酸浓度。病例组采用阳性和阴性症状量表(PANSS)评定精神病理症状。结果:病例组血浆白蛋白和尿酸浓度低于对照组(P均<0.05);家族史阳性患者白蛋白和胆红素浓度低于家族史阴性患者(P均<0.05);家族史阳性患者病程与尿酸浓度呈负相关(r=-0.50,P<0.05),阴性症状分与白蛋白和尿酸浓度呈负相关(r=-0.37,-0.41,P<0.05)。结论:精神分裂症首发患者血浆非酶抗氧化能力下降,而且可能与阴性症状、家族史有关。     

胞二磷胆碱对原代培养的中脑多巴胺能神经元的保护作用及其机制

为了研究胞二磷胆碱(citicoline,CC)对6-羟多巴胺(6-OHDA)诱导的Parkinson病体外细胞模型中的多巴胺能神经元的保护作用及其机制,本研究采用MTT法检测细胞活力;应用Fluo3/AM荧光染料,并通过流式细胞仪检测细胞内钙离子[Ca2+]i浓度;罗丹明123检测线粒体膜电位(ΔΨm);罗丹明123和PI荧光双染,在荧光显微镜下观察细胞膜通透性和细胞凋亡;乳酸脱氢酶(LDH)试剂盒检测培养上清中LDH的漏出;TH免疫组化染色鉴定多巴胺能神经元。实验分成三组:(1)对照组:即原代培养细胞;(2)6-OHDA损伤组:即原代培养细胞加6-OHDA;(3)CC保护组:原代培养细胞中分别加2、1、0.1、0.01和0.001mmol/LCC后,再加6-OHDA。结果显示:与6-OHDA组相比,1、0.1、0.01和0.001mmol/LCC组细胞活力增加(P<0.01);[Ca2+]i浓度下降和ΔΨm升高(P<0.01);除了0.001mmol/LCC组外,各CC组LDH漏出率明显低于6-OHDA组(P<0.01)。以上结果提示:在体外Parkinson病细胞模型中,CC可能通过保护神经元细胞膜,提高线粒体膜电位,增加细胞活力,降低[Ca2+]i浓度,减少LDH漏出等途径削弱6-OHDA的神经毒性作用,发挥其对神经元的保护作用。     

乳腺癌改良根治术后调强放疗与常规放疗疗效及对心肺的影响

目的:探讨乳腺癌改良根治术后调强放疗与常规放疗的疗效及对心肺的影响。方法:选择乳腺癌改良根治术患者60例,按照不同放疗方法分为观察组30例与对照组30例。观察组患者行调强放疗,对照组患者行常规放疗。比较两组近期,放疗前后心肌酶肌钙蛋白和肺功能变化,以及患肺和心脏受照剂量变化。结果:两组近期总有效率比较无显著差异(P>0.05)。两组放疗后肌钙蛋白水平较放疗前升高(P<0.05);观察组放疗后肌钙蛋白水平低于对照组(P<0.05)。两组放疗后射血分数较放疗前降低,而LADs和LVDd较治疗前升高(P<0.05);观察组放疗后射血分数高于对照组,而LADs和LVDd低于对照组(P<0.05)。两组患侧肺脏指数V95比较无显著差异(P>0.05);观察组患侧肺脏指数V105和V110低于对照组(P<0.05)。观察组心脏指数V30、V40和V50低于对照组(P<0.05)。结论:乳腺癌改良根治术后调强放疗与常规放疗疗效相当,而调强放疗对心脏和肺脏影响小,可减轻心脏和肺脏的放射性损伤。     

联合检测7种自身抗体在非小细胞肺癌中的诊断价值

目的探讨7种肿瘤相关抗原自身抗体在非小细胞肺癌诊断中的应用价值。方法回顾性分析非小细胞肺癌患者443例、体检健康人群405例,采用ELISA法检测各组血清中7种自身抗体的水平,分析抗体水平组间及阳性率差异,绘制ROC曲线分析单个抗体和联合检测的诊断效能,结合病理诊断结果分析联合检测的阳性率与肺癌临床病理特征的关系。结果与对照组相比,非小细胞肺癌组中p53(P<0.001)、SOX2(P=0.049)、GAGE7(P=0.040)、GBU4-5(P=0.005)、MAGEA1(P=0.025)、CAGE(P=0.036)血清浓度水平高于对照组。非小细胞肺癌组中p53(P<0.001)、SOX2(P<0.001)、GAGE7(P<0.001)、GBU4-5(P<0.001)、MAGEA1(P<0.001)、CAGE(P<0.001)抗体阳性率显著高于对照组。7种自身抗体联合检测的敏感性为56.66%,特异性为93.58%,AUC为0.751。临床病理特征分析显示:联合检测7种自身抗体与PD-L1的表达具有相关性(P=0.042),与其余指标无相关性。结论联合检测7种自身抗体阳性率与非小细胞肺癌有相关性,是肺癌筛查和诊断的有效辅助手段。     

缺硒所致心肌线粒体膜氧化损伤的研究

Keshan disease (KD) is an endemic cardiomyopathy with membrane damage of the myocardial mitochondria. This paper reports the results of feeding guinea pigs with a forage obtained from KD endemic area. The selenium (Se) content and glutathione peroxidase activity in blood, tissues, mitochondria, microsome and supernatant of myocardium and liver cells of the experimental group were decreased. Additionally, the activity of glutathione-S-transferase was also decreased to some extent, instead of being increased in normal cases, and the content of lipid peroxide and hydroperoxide was increased. At the same time, cardiolipin in mitochondria, and the activity of cytochrome C oxidase (CCO, an enzyme binding with mitochondrial membrane) were also reduced accompanied with oxidative damage and disorder of function of the membrane. Anyhow, when exogenous cardiolipin was added in the purified endemic CCO solution, it was capable of restoring CCO activity significantly. The significance of Se deficiency and unbalanced diet in pathogenesis of Keshan disease is discussed.     

实验性糖尿病大鼠心肌细胞膜完整性的改变

应用电生理和辣根过氧化物酶示踪技术观察链脲佐菌素引起的实验性糖尿病大鼠心肌细胞膜完整性的变化。实验结果表明,糖尿病大鼠心肌细胞动作电位波幅、最大舒张电位,阈电位和最大除极速度均比对照动物明显减低(P<0.001),而复极不同水平的动作电位时程比对照动物显著延长(P<0.001),糖尿病大鼠心肌中辣根过氧化物酶阳性的肌细胞数明显多于对照动物(P<0.05)。这些结果说明,糖尿病大鼠心肌细胞膜存在损伤的电位变化,并有肌膜通透性增大。提示心肌细胞膜完整性的损害在糖尿病性心肌病的发生机理中可能起一定作用。     

Increased sarcolemmal membrane permeability of cardiac muscle cells in rats fed grains cultivated in a Keshan disease endemic area: a study with horseradish peroxidase as a tracer

The alteration of sarcolemmal membrane permeability of cardiac muscle cells in rats fed grain from a Keshan disease (KD) endemic area was studied with horseradish peroxidase (HRP) as a tracer. Weanling male rats were divided at random into three groups and fed the following three diets, respectively, for 3 months: a diet with grain from a KD endemic area (Group A), a diet with grain from a KD nonendemic area (Group B), and standard laboratory chow (Group C). At the end of the experiment, HRP was injected intravenously and localized in the ventricular myocardium by light microscopy. The experimental results showed that the percentage of cardiac muscle cells containing HRP reaction product in rats fed grain from the KD endemic area was significantly greater than that in rats fed grain from nonendemic area and standard laboratory chow. This suggests that the sarcolemmal membrane permeability of cardiac muscle cells in rats of Group A was markedly increased. The distribution of cardiac muscle cells with increased sarcolemmal membrane permeability was similar to that seen in the myocardium of KD patients. The present study suggests that the abnormal membrane permeability of cardiac muscle cells may play an important role in the pathogenesis of myocardial necrosis in KD.     

Microvascular changes in rat glomeruli as a consequence of small differences in selenium exposure.

This paper evaluates the effect of small differences in selenium exposure, within the safe range, on the glomerular vascular tufts of rats fed high-sucrose diets. In the first experiment male Wistar rats were housed in galvanized cages and were provided sucrose-based diets to induce a mild chronic insult to the microcirculation. One group of rats received the diet prepared to contain 0.10 mg Se/kg and another group 0.21 mg Se/kg. To assure that the galvanized metal cages were not influencing the results of the experiment this protocol was repeated in a second experiment wherein rats were housed in stainless steel cages. The levels of Se used supported normal activity of the long-term indicator of Se sufficiency, erythrocyte glutathione peroxidase. In both experiments rats fed diets containing 0.21 mg Se/kg had larger Bowman's capsules (P < 0.01) and vascular tufts (P < 0.01). Vascular tufts from these rats also contained a higher proportion of open capillary lumen (P < 0.01), contained less cytoplasmic and extracellular material (P < 0.001), and had larger nuclei (P < 0.001) than those fed 0.10 mg Se/kg. A third study was designed to determine if the selenium-dependent differences in nuclear size were indicative of this being a site of incorporation. Year-old rats subjected to the same protocol as those in the second experiment were given 75Se, by injection into the femoral vein, to label the sites of incorporation. Glomeruli were purified and subjected to subcellular fractionation. Ninety percent of the radioactivity was associated with the crude nuclear fraction. Purification of the crude nuclear fraction demonstrated that the radioactivity was associated with the nuclei.     

袖状胃切除术对高脂饮食诱导肥胖大鼠肠道屏障的影响

目的研究袖状胃切除术对高脂饮食诱导肥胖大鼠肠道屏障的影响。方法建立高脂饮食诱导肥胖大鼠模型共30只,随机分为普通饮食组(CD,n=10)、假手术组(SO,n=10)和袖状胃切除组(SG,n=10),术后4周时分别检测24 h尿乳果糖/甘露醇比值(L/M)、门静脉血清内毒素水平和小肠黏膜紧密连接蛋白claudin-1和occludin表达水平。结果术后4周时,SG组大鼠体质量明显低于CD组(P0.001)和SO组(P0.001)。SG组大鼠24 h尿L/M值明显低于CD组(P0.001)和SO组(P0.01)。SG组门静脉血清内毒素水平明显低于CD组(P0.01)和SO组(P0.05)。术后4周时,SG组大鼠小肠黏膜中claudin-1表达水平明显高于CD组(P0.001)和SO组(P0.01),occludin表达水平明显高于CD组(P0.001)和SO组(P0.001)。结论袖状胃切除术可使高脂饮食诱导的肥胖大鼠体质量下降,降低24 h尿L/M值和门静脉血清内毒素水平,提高小肠黏膜中claudin-1和occludin蛋白的表达水平。     

冷刺激条件下硒和维生素E对大鼠心脏内血管活性物质的影响

目的：用低硒／维生素E(Se／VE)饲料喂养的大鼠动物模型,施以冰冰在刺激,观察Se,VE对心肌血管活性物质的影响。方法：用60只Wistar大鼠,按体重和性别随机分为低硒／维生素EI组（Se/VEDGI）及上述每kg饲料补硒（亚硒酸钠）0.1mg（Se／VEDGI＋Se）组、补a－VE100mg（Se／VEDGI＋VE）组、联合补Se,VE（Se／VEDGI＋Se／VE）组、低硒／维生素EII组（Se／VEDGII）和常规饲料组（SG)等六组。饲养70d,测定各组动物心肌内皮素（ET）,一氧化氮（NO）,去甲管上腺素（NE）,血管紧张素II（Ang－II）,单胶氧化酶（MAO－A）,超氧化物歧化酶（SOD）,谷胱甘肽过氧化物酶（GSH－Px）,脂褐素（lipofuscin）等水平。结果：Se／VEDG组心肌ET,Ang－II含量明显高于其它组;NO含量明显低于其它组;心肌NE水平增高,而特异性分解NE的MAO－A活性降低;心肌Lipofusein含量明显增加;SOD,GSH－Px含量降低。补Se组、补SE／VE组、低Se/VEII组和对照组上述指标活性明显改善。结论：冷刺激条件下硒和维生素E对大鼠心脏内血管活性物质有明显影响。     

四逆汤对异丙肾上腺素引起的大鼠心肌纤维化和TGF-β_1表达的影响

目的:观察四逆汤对异丙肾上腺素引起的大鼠心肌纤维化的干预作用并探讨其相关机制。方法:Wistar大鼠随机分为对照组、模型组和四逆汤组。模型组及四逆汤组给予注射异丙肾上腺素,而对照组注射生理盐水。四逆汤组给予四逆汤灌胃,对照组和模型组均给予生理盐水灌胃。4周后,各组测定左室心功能、心肌羟脯氨酸水平;测定血浆中血管紧张素Ⅱ(AngⅡ)和转化生长因子-β1(TGF-β1)水平;通过免疫组化方法检测心肌TGF-β1蛋白的表达;RT-PCR法检测TGF-β1mRNA表达。结果:(1)模型组羟脯氨酸水平明显高于对照组和四逆汤组,而四逆汤组明显高于对照组(P0.05);(2)四逆汤组与模型组比较,明显改善心肌舒张功能(P0.05);(3)模型组血浆AngⅡ及TGF-β1水平明显高于四逆汤组和对照组(P0.05);(4)模型组心肌TGF-β1蛋白和mR-NA表达明显高于四逆汤组和对照组(P0.05)。结论:四逆汤可以有效抑制异丙肾上腺素所致的大鼠心肌纤维化,其机制可能与减少AngⅡ生成,抑制大鼠心肌TGF-β1的表达有关。     

Altered diaphragm muscle action potentials in Zucker diabetic fatty (ZDF) rats

The Zucker diabetic fatty (ZDF) rat is a model of type 2 diabetes, being characterized by obesity, diabetes, and dyslipidemia. In vitro studies tested the hypothesis that diaphragm muscle from ZDF rats has abnormal resting membrane potential and action potentials, similar to type 1 diabetic rodents. Resting membrane potential was comparable for muscle from ZDF and control rats. Diaphragm from ZDF rats had augmented action potential peak height (92.1 mV versus 82.4 mV, P<0.00001), overshoot (15.6 mV versus 8.1 mV, P<0.001) and area (80.7 mV ms versus 68.6 mV ms, P<0.001) compared with that from controls. Action potential rate of depolarization and repolarization were not affected. The K(+) blocker, 3,4-diaminopyridine, augmented action potential duration and area of muscle from ZDF and controls, but without significant differences between animal groups. These findings in ZDF rats contrast with type 1 diabetic rats, suggesting that isolated hyperglycemia differs from hyperglycemia combined with other metabolic perturbations with respect to diaphragm electrophysiological derangements.     

低硒低维生素E粮对大鼠红细胞变形性的影响

以低硒（Ｓｅ）、低维生素Ｅ（ＶＥ）粮饲养大鼠，观察其血液流变学指标变化。结果表明，低Ｓｅ、低ＶＥ粮饲养大鼠的红细胞（ＲＢＣ）变形性、ＧＳＨ－ＰＸ和ＣｕＺｎＳＯＤ活力降低，ＲＢＣ压积、ＲＢＣ聚集性、ＲＢＣ聚集指数、脂质过氧化物增高。结果提示，Ｓｅ可能通过改变红细胞内表膜面Ｓｐｅｃｔｒｉｎ蛋白与ＲＢＣ膜骨架结合状态以及Ｓｅ和ＶＥ抗氧化损伤保护细胞膜结构完整性的作用，影响ＲＢＣ的变形性。     

Abnormality of epiphyseal plate induced by selenium deficiency diet in two generation DA rats

This study aimed to observe the effects of Se deficiency on epiphyseal plates of two generation DA rats fed with artificial total synthetic low Se diet. All F0 and F1 DA rats were fed with synthetic low Se diet (SeD group) and low Se diet supplied with Se (SeS group). The levels of selenium and enzyme activities of GPx were detected in plasma of the rats. General growth of bone and articular cartilage was measured macroscopically and microscopically. The epiphyseal plate of femur heads or tibia were obtained to histological and immunohistochemical examinations. The cartilage from left knee joints and femur heads was used to detect the gene expression of collagens, ADAMTSs and several selenoproteins by RT‐qPCR. Two generation SeD rats showed Se insufficiency status. The thicknesses of the femur and tibial epiphyseal plates in both F0 and F1 SeD rats were significantly less than that of SeS rats. In F1 generation, SeD rats showed much fewer proliferative chondrocyte layers than SeS ones. Importantly, two generation SeD rats both showed significantly more serious pathological changes of epiphyseal plates. In two generation rats, gene expressions of COL II, GPx1 and GPx4 were significantly down‐regulated in SeD rats than SeS ones; meanwhile ADAMTS‐4 showed an up‐regulated expression in cartilage. Dietary Se deficiency can apparently cause epiphyseal plate lesion and decrease cartilage type II collagen production and GPx1 activity in two generation DA rats fed with the artificial total synthesis low Se diet.