罗格列酮联合胰岛素对糖尿病大鼠氧化应激及血脂水平的影响

摘要 目的：探讨罗格列酮（RSG）联合胰岛素（INS）对糖尿病大鼠的氧化应激和血脂水平的影响。方法：30只健康雄性Wistar大鼠,随机分为3组：健康对照组、DM模型组和RSG+INS组,每组10只。采用链脲佐菌素（STZ）造模法进行糖尿病大鼠模型诱导。此后以RSG （3 mg/kg/day）灌胃,INS （2.25 U/kg/day）皮下注射,均连续给药8周,对RSG+INS组大鼠进行干预治疗。每2周定期记录各组大鼠的体重和血糖值1次;药物干预治疗8周后,取各组大鼠血清,对血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、糖化血红蛋白（HbA1c）和丙二醛（MDA）的含量以及超氧化物歧化酶（SOD）和谷胱甘肽（GSH）的活性进行检测;应用苏木素碱性复红苦昧酸（HBFP）染色分析心肌形态变化。结果：RSG联合INS组治疗糖尿病大鼠,导致血糖发生时间依赖性下降（均P<0.05）;药物干预处理8周后,RSG+INS组大鼠的血清TC、TG、LDL和HbA1c水平均显著低于DM模型组,而HDL显著高于DM模型组（均P<0.05）;与DM模型组相比,RSG+INS组大鼠的血清MDA含量显著下降,而SOD和GSH活性则显著升高（均P<0.05）;与DM模型组相比,RSG+INS组心肌缺血/氧程度减轻。结论：RSG联合INS可有效对抗糖尿病大鼠体内的氧化应激损伤,改善糖尿病大鼠的脂代谢异常情况,并对心肌组织有一定的保护作用。     

2型糖尿病患者幽门螺杆菌感染与超敏c反应蛋白、血脂情况的关系

目的：探讨2型糖尿病（T2DM）患者幽门螺杆菌（HP）感染与超敏c反应蛋白（hs-CRP）、血脂水平的关系。方法：以2009年1月1日至2009年12月31日在我院体检的683例2型糖尿病患者为研究对象,根据HP感染情况分成HP阳性组（n=306）和HP阴性组（n=377）,采用单因素和多因素Logistic回归分析方法,分析HP感染与hs-CRP、血脂水平的关系。结果：（1）HP阳性组的hs-CRP水平高于HP阴性组（1.14mg/L vs 0.96mg/L）,差异有统计学意义（P〈0.05）。（2）HP阳性组的血脂异常率（59.8%vs 50.7%）和hs-CRP异常率（20.9%vs 14.3%）均高于HP阴性组,差异均有统计学意义（均P〈0.05）。（3）单因素Logistic回归分析显示,血脂异常和hs-CRP异常对HP阳性的OR值及分别为1.449和1.582,均有统计学意义（均P〈0.05）,多因素Logistic回归分析显示,hs-CRP异常对HP阳性的OR值为1.509,有统计学意义（P〈0.05）。结论：2型糖尿病患者,HP感染可能通过增高hs-CRP水平,影响脂质代谢,触发一系列生物、生物化学级联反应,可使患者并发心血管病变的风险性增高。     

PPARgamma-dependent and -independent effects of rosiglitazone on lipotoxic human pancreatic islets

We explored the in vitro effects of Rosiglitazone (RZG), a PPARγ agonist, on human pancreatic islet dysfunctions induced by chronic free fatty acid exposure. We demonstrated that RZG beneficial effects on insulin secretion and apoptosis did not imply PDX-1 or insulin gene modulation. It rather involved, through a PPARγ-dependent mechanism, a reduction of iNOS overexpressed in lipotoxic islets. This reduction likely led to the restoration of ATP level and insulin secretion as well as the decrease in apoptosis. More interestingly, we also demonstrated that RZG beneficial effects involved PPARγ-independent mechanisms. RZG treatment led to a limitation of oxidative stress exemplified by an increase of GPx and SOD expression. It also increased UCP2 expression that seemed to display antioxidant action in this model. Thus, RZG did not appear to exert a direct action on insulin expression but rather an indirect action on insulin secretion and apoptosis, through PPARγ-dependent and -independent mechanisms, via regulation of nitrogen and oxygen reactive species injury.     

Structure-activity relationships of rosiglitazone for peroxisome proliferator-activated receptor gamma transrepression

Anti-inflammatory effects of peroxisome proliferator-activated receptor gamma (PPRAγ) ligands are thought to be largely due to PPARγ-mediated transrepression. Thus, transrepression-selective PPARγ ligands without agonistic activity or with only partial agonistic activity should exhibit anti-inflammatory properties with reduced side effects. Here, we investigated the structure-activity relationships (SARs) of PPARγ agonist rosiglitazone, focusing on transrepression activity. Alkenic analogs showed slightly more potent transrepression with reduced efficacy of transactivating agonistic activity. Removal of the alkyl group on the nitrogen atom improved selectivity for transrepression over transactivation. Among the synthesized compounds, 3l exhibited stronger transrepressional activity (IC₅₀: 14 μM) and weaker agonistic efficacy (11%) than rosiglitazone or pioglitazone.     

Occurrence of parasympathetic vasodilator fibers in the lower lip of the guinea-pig

The present study was designed to examine whether there are parasympathetic vasodilator fibers in the lower lip of the guinea-pig. Electrical stimulation of the central cut end of the lingual nerve of guinea-pigs evoked intensity- and frequency-dependent decreases in lower lip blood flow and systemic arterial blood pressure (SABP). Pretreatment with guanethidine, a postganglionic sympathetic nerve blocker and antihypertensive drug (30 mg kg⁻¹, s.c., 24 h prior to experiments), reduced the magnitude of the decrease in SABP while the intensity- and frequency-dependent increases of the lip blood flow occurred by the lingual nerve stimulation only on the side ipsilateral to stimulation. Increases in the lip blood flow evoked by lingual nerve stimulation in guanethidine pretreated guinea-pigs were reduced by hexamethonium (an autonomic ganglion cholinergic blocker) in a dose-dependent manner. When fluoro-gold (a retrograde neural tracer) was injected into the lower lip, labeled neurons were observed in the ipsilateral otic ganglion. The present study indicates the presence of parasympathetic vasodilator fibers originating from the otic parasympathetic ganglion in the guinea-pig lower lip, similar to those reported previously in rats, cats, rabbits and humans.     

Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators

Resistin is a cysteine-rich protein postulated to be a molecular link between obesity and type 2 diabetes. The aim of this study was to investigate the role of PPAR gamma in the regulation of resistin expression in human primary macrophages. Fluorescent real-time PCR (Taqman) analysis of resistin expression across a range of human tissues showed that resistin is highly expressed in bone marrow compared to other tissues. Taqman analysis and Western blotting showed that rosiglitazone decreased resistin expression at both the mRNA and protein levels in human primary monocyte-derived macrophages in vitro. Resistin expression was reduced by up to 80% after exposure to 100 nM rosiglitazone for 96 h. Bioinformatics analysis of the genomic sequence upstream of the resistin coding sequence identified several putative PPAR response elements of which one was shown to bind PPAR gamma using electrophoretic mobility shift assays. Our data support a direct role for PPAR gamma in the regulation of resistin expression.     

缩唇腹式呼吸联合呼吸操训练对慢性阻塞性肺疾病患者血气分析指标、肺功能和生活质量的影响

目的:探讨缩唇腹式呼吸联合呼吸操训练对慢性阻塞性肺疾病(COPD)患者血气分析指标、肺功能和生活质量的影响。方法:选取2020年1月-2021年4月期间就诊于我院的82例COPD患者,根据随机数字表法分为对照组(缩唇腹式呼吸训练,41例)和研究组(缩唇腹式呼吸结合呼吸操训练,41例),对比两组疗效、血气分析指标[动脉血二氧化碳分压(PaCO₂)、血氧分压(PaO₂)、血氧饱和度(SaO₂)]、肺功能[用力肺活量(FVC)、第1秒用力呼气容积(FEV₁)、第1秒用力呼气容积所占FVC的比例(FEV₁/FVC)]、生活质量[圣乔治呼吸问卷(SGRQ)评分]、6分钟步行试验(6MWT)距离、BODE指数。结果:研究组的临床总有效率明显高于对照组(P<0.05)。研究组治疗3个月后PaO₂、SaO₂高于对照组,PaCO₂低于对照组(P<0.05)。研究组治疗3个月后FEV₁、FVC、FEV₁/FVC高于对照组(P<0.05)。研究组治疗3个月后6MWT距离长于对照组,SGRQ评分、BODE指数低于对照组(P<0.05)。结论:缩唇腹式呼吸联合呼吸操训练可改善COPD患者血气分析指标,提高肺功能和运动耐力,改善生活质量,疗效显著。     

Simultaneously quantitative measurement of comprehensive profiles of esterified and non-esterified fatty acid in plasma of type 2 diabetic patients

Fatty acids, having intimate relationship with type 2 diabetes mellitus (DM2), are not only the main energy source as nutrients, but also signaling molecules in insulin secretion. In this work, we developed a two-step rapid method to comprehensive profiling of esterified fatty acid (EFA) and non-esterified fatty acid (NEFA) using KOH–CH₃OH to methylate EFA followed by H₂SO₄–CH₃OH to methylate NEFA. Its applications to fatty acids profiling of type 2 diabetic patients and health controls were also presented. The t-test results informed that 16 NEFAs and 7 EFAs had distinct differences between type 2 diabetes and health controls. Furthermore, quantitative alterations of fatty acids in plasma of type 2 diabetic patients treated with rosiglitazone were obtained by this method. Our research results indicated that the dynamic changes of NEFAs are various. Some decreased linearly, such as C18:0, C18:3n-6 and C22:6, and some changed nonlinearly, such as C18:3n-3 and C22:4. All results informed that fatty acid profiles could provide comprehensive and accurate information for not only discrimination between DM2 patients and health controls, but also evaluation alterations of fatty acids during therapeutic process.     

Genome-wide screening of alpha-tocopherol sensitive genes in heart tissue from alpha-tocopherol transfer protein null mice (ATTP(-/-))

Alpha-tocopherol transfer protein (ATTP) null mice (ATTP(-/-)) have a systemic deficiency of alpha-tocopherol (AT). The heart AT levels of ATTP(-/-) are <10% of those in ATTP(+/+) mice. The genomic responses of heart to AT deficiency were determined in 3 months old male ATTP(-/-) mice and compared with their ATTP(+/+) littermate controls using Affymetrix 430A 2.0 high density oligonucleotide arrays. Differential analysis of approximately 13000 genes identified repression of genes related to immune system and activation of genes related to lipid metabolism and inflammation with no significant change in the expression of classical antioxidant genes (catalase, superoxide dismutase, glutathione peroxidase) in ATTP(-/-) as compared to ATTP(+/+) mice. The present data identifies novel classes of AT sensitive genes in heart tissue.