消化系恶性肿瘤患者血清与腹水中细胞因子活性变化

目的研究消化系恶性肿瘤（ＤＭＴ）患者血清与腹水中内源性ＩＬ２,ＩＬ６,ＩＬ８,ＴＮＦα和ＩＦＮγ的生物学活性．方法应用ＥＬＩＳＡ法检测了１５例ＤＭＴ患者（肝癌１１例,胆总管癌１例,胰腺癌１例,胃癌１例,直肠癌１例）血清与腹水中５种细胞因子活性,并与６例肝硬变（ＬＣ）患者和８例正常成人进行了比较分析．结果ＤＭＴ患者血清ＩＬ２,ＩＬ６的生物学活性显著低于ＬＣ（Ｐ＜００５）;腹水中ＩＬ２,ＩＬ８活性显著低于ＬＣ组（Ｐ＜００１）,而ＩＬ６和ＩＦＮγ活性则高于ＬＣ组（Ｐ＜００１,００５）．ＤＭＴ患者血清中ＩＬ６,ＩＬ８活性明显高于正常成人组（Ｐ＜００５）;ＩＬ２,ＩＦＮγ则低于正常成人组,但缺乏显著性．肝癌血清和腹水中ＩＬ２活性显著高于非肝癌组（Ｐ＜００５）;而ＩＬ６活性则相对降低（Ｐ＜００５）．结论恶性肿瘤患者血清中ＩＬ２和ＩＦＮγ活性低于正常人,是ＤＭＴ患者抗肿瘤免疫功能缺陷的标志．ＩＬ６对于预测ＤＭＴ患者的预后具有重要的意义     

细胞因子对树突状细胞抗肝癌作用的影响

目的研究人血树突状细胞（ＤＣ）和细胞因子ＴＮＦ,ＧＭＣＳＦ或ＩＦＮγ联合ＤＣ对淋巴因子和ＰＨＡ激活的杀伤细胞（ＬＰＡＫ细胞）体外杀伤人肝癌细胞株ＢＥＬ７４０２的影响．方法实验分为Ｌ组（ＬＰＡＫ）,Ｄ组（ＬＰＡＫ＋ＤＣ）,Ｔ１组（ＬＰＡＫ＋ＤＣ＋ＴＮＦ５０００ｋＵ／Ｌ）,Ｔ２组（ＬＰＡＫ＋ＤＣ＋ＴＮＦ５００ｋＵ／Ｌ）,Ｇ１组（ＬＰＡＫ＋ＤＣ＋ＧＭ－ＣＳＦ５００ｋＵ／Ｌ）,Ｇ２组（ＬＰＡＫ＋ＤＣ＋ＧＭ－ＣＳＦ１００ｋＵ／Ｌ）,Ｉ１组（ＬＰＡＫ＋ＤＣ＋ＩＦＮγ５００ｋＵ／Ｌ）和Ｉ２组（ＬＰＡＫ＋ＤＣ＋ＩＦＮγ１００ｋＵ／Ｌ）．每组效靶细胞比分别采用５∶１和１０∶１两种．培养４８ｈ后用中性红比色法检测细胞毒活性．结果Ｌ,Ｄ,Ｔ２和Ｔ１组的细胞毒活性依次增强,各组间差异有显著性（Ｐ＜００１）．Ｇ１和Ｇ２组均高于Ｄ组（Ｐ＜００１）,但Ｇ１,Ｇ２组间差异无显著性．Ｉ１,Ｉ２组与Ｄ组相比,也无显著性差异．随效靶比增加,各组细胞毒活性均相应增强．结论ＤＣ能增强ＬＰＡＫ细胞对肝癌细胞ＢＥＬ７４０２的细胞毒活性;ＴＮＦ或ＧＭＣＳＦ与ＤＣ联用,两者有协同作用;但与ＩＦＮγ联用,则无进一步增强作用     

溃疡性结肠炎患者血清TNFα和IL-8的临床研究

目的研究血清ＴＮＦα和ＩＬ８在溃疡性结肠炎（ＵＣ）发生发展中的作用和意义．方法利用双抗体夹心ＥＬＩＳＡ法测定３３例ＵＣ患者（男１７例，女１６例；年龄２５岁～６７岁；病程２个月～１５ａ；轻型７例，中型２０例，重型６例）及正常对照者４０例，血清ＴＮＦα和ＩＬ８水平．结果活动性ＵＣ患者血清ＴＮＦα（２６２２ｎｇ／Ｌ±２０ｎｇ／Ｌｖｓ１４６２ｎｇ／Ｌ±２５ｎｇ／Ｌ，Ｐ＜００５）和ＩＬ８（１１１８ｎｇ／Ｌ±２６ｎｇ／Ｌｖｓ５７５ｎｇ／Ｌ±４０ｎｇ／Ｌ，Ｐ＜００５）水平明显增高，并与病情的轻重和病变的范围有关（Ｐ＜００５）．结论ＵＣ患者血清ＴＮＦα和ＩＬ８水平增高可能与ＵＣ的发生发展有关，它可作为ＵＣ病情判断的指标．     

自由基在实验性胃癌及癌前病变发生中的作用

目的探讨自由基在胃癌及其癌前病变发生中的作用．方法将１００只Ｗｉｓｔａｒ大鼠分为２组，实验组（７０只），给予１００ｍｇ／Ｌ甲基硝基亚硝基胍（ＭＮＮＧ）水溶液自由饮用３０ｗｋ，对照组（３０只）饮用自来水．选５个时相点，动态观察ＭＮＮＧ诱发实验性胃癌及其癌前病变过程中大鼠体内丙二醛（ＭＤＡ）、脂质过氧化物（ＬＰＯ）、谷胱甘肽过氧化物酶（ＧＳＨＰＸ）及超氧化物歧化酶（ＳＯＤ）等的变化情况．结果在实验组，ＭＤＡ平均含量在５２ｗｋ非常显著地大于０ｗｋ（Ｐ＜００１），并显著地大于１６ｗｋ以前（Ｐ＜００５）．胃癌组织ＭＤＡ含量显著高于胃癌癌前病变组织（Ｐ＜００５）．癌组织ＬＰＯ的含量显著高于癌前病变组织（Ｐ＜００５）．实验组，总ＳＯＤ和ＣｕＺｎＳＯＤ活性在５２ｗｋ明显低于１６ｗｋ之前（分别为Ｐ＜００５和Ｐ＜００１）．癌组织ＣｕＺｎＳＯＤ含量非常显著地小于正常胃粘膜（Ｐ＜００１），亦明显低于胃粘膜异型增生和肠上皮化生（Ｐ＜００５）．在３０ｗｋ和５２ｗｋＧＳＨＰＸ活性显著低于１６ｗｋ以前．结论自由基在实验性胃癌及其癌前病变发生中具有一定作用，自由基清除剂可能对胃癌的综合防治具有积极意义     

类风湿关节炎病人血清细胞因子水平以及与炎症指标的相关性

目的：进一步研究细胞因子在类风湿关节炎（ＲＡ）中的作用以及与疾病的关系。方法：随机就诊的７２名门诊及住院ＲＡ病人红细胞沉降率（ＥＳＲ）、Ｃ反应蛋白（ＣＲＰ）以及细胞因子白细胞介素１α（ＩＬ１α）、ＩＬ１β、ＩＬ２、ＩＬ６、肿瘤坏死因子α（ＴＮＦα）、粒细胞单核细胞集落刺激因子（ＧＭＣＳＦ）被测定。全部数据用于ＲＡ病人细胞因子水平的研究，并对细胞因子与炎症指标的相关性进行探讨。结果：ＲＡ病人血清ＧＭＣＳＦ、ＴＮＦα水平较健康对照组明显增高（Ｐ＜０００１）。ＩＬ６、ＧＭＣＳＦ与炎性指标ＥＳＲ（ｒ＝０２６，Ｐ＜００１；ｒ＝０２８，Ｐ＜００２）和ＣＲＰ（ｒ＝０４０，Ｐ＜００００１；ｒ＝０４７，Ｐ＜００００１）呈正相关。结论：ＲＡ病人血清ＩＬ６、ＧＭＣＳＦ、ＴＮＦα较其他细胞因子与ＲＡ疾病有更密切的相关性。细胞因子作为重要的免疫物质参与炎症反应在ＲＡ的病理过程中起到了重要作用。     

肝炎后肝硬变肝损害与细胞免疫功能(英文)

目的研究肝炎后肝硬变（ＰＨＣ）患者的细胞免疫状态及其与肝功能损害的关系．方法５１例ＰＨＣ患者，包括ＣｈｉｌｄＰｕｐｈＡ级２０例、Ｂ例１８例、Ｃ级１３例和２２例健康对照者，外周血经用ＦｉｃｏｌＨｙｐａｑｕｅ梯度离心分离单个核细胞后，采用３ＨＴｄＲ掺入技术测定了淋巴细胞转化，ＩＬ２和ＮＫ细胞活性．结果在ＰＨＣ患者淋巴细胞转化指数（ＳＩ）、ＩＬ２活性（ＳＩ）和ＮＫ细胞活性（％）较对照组均明显降低（１８１±１３０ＶＳ３４９±２１７，Ｐ＜００１；８１±６０ＶＳ１３６±５８，Ｐ＜００１；４０３±２１７ＶＳ６１３±２０５，Ｐ＜００１）．免疫功能缺陷与ＣｈｉｌｄＰｕｐｈ分级有关，Ｃ级明显低于Ａ、Ｂ级（Ｐ＜００１），Ｂ级低于Ａ级（Ｐ＜００５）．结论ＰＨＣ患者存在细胞免疫功能缺陷，且与肝损害程度有关．     

一氧化氮介导的细胞因子对大鼠胰岛素分泌的影响

目的观察白细胞介素１β（ＩＬ１β）、白细胞介素６（ＩＬ６）对胰岛细胞一氧化氮（ＮＯ）生成、胰岛素分泌的影响。方法在体外单层培养的大鼠胰岛细胞上，分别应用分光光度法、放免双抗体法检测ＩＬ１β、ＩＬ６及其联合对胰岛细胞ＮＯ生成、胰岛素分泌的影响，并进一步观察一氧化氮合酶抑制剂ＮＧ单甲基Ｌ精氨酸（ＬＮＭＭＡ）的作用。结果ＩＬ１β能诱导大鼠胰岛细胞ＮＯ的生成，同时显著抑制胰岛素基础分泌及葡萄糖刺激的胰岛素释放。ＬＮＭＭＡ能阻断这些作用（Ｐ值均＜０．００１）。ＩＬ６不能诱导胰岛细胞的ＮＯ生成（Ｐ值＞０．０５），对胰岛素分泌有促进作用，但对葡萄糖刺激的胰岛素释放有明显的抑制作用（Ｐ值＜０．００１）。ＩＬ６与ＩＬ１β联合作用时，不能影响ＩＬ１β对胰岛素释放的抑制作用及其诱导的ＮＯ生成（Ｐ值均＞０．０５）。结论ＩＬ１诱导的胰岛细胞损害可能由ＮＯ介导。ＩＬ６诱导胰岛细胞功能改变的作用方式与ＩＬ１β不同，可能与其不能诱导ＮＯ生成有关。     

Western印迹方法测定血清中胰岛素样生长因子结合蛋白-3水平

目的　研究正常人及生长激素分泌异常病人血清中胰岛素样生长因子结合蛋白３（ Ｉ Ｇ Ｆ Ｂ Ｐ３） 的水平。方法　本文采用 Ｗｅｓｔｅｒｎ 印迹方法测定２０ 例正常人,３３ 例活动性肢端肥大症病人和３４ 例特发性生长激素缺乏症（ Ｉ Ｇ Ｈ Ｄ） 病人血清 Ｉ Ｇ Ｆ Ｂ Ｐ３ 水平。结果　正常成人血清中存在五种分子量不同的 Ｉ Ｇ Ｆ Ｂ Ｐ, Ｉ Ｇ Ｆ Ｂ Ｐ３ 含量为最高。本文测定了２０ 例正常成人和６７ 例生长激素分泌异常患者血清 Ｉ Ｇ Ｆ Ｂ Ｐ３ 的相对光密度（ Ｒ Ｏ Ｄ） ,正常人血清 Ｉ Ｇ Ｆ Ｂ Ｐ３ 含量为（１ ．１ ±０ ．４） Ｒ Ｏ Ｄ,活动性肢端肥大病人为（２ ．７ ±１ ．２） Ｒ Ｏ Ｄ,明显高于正常成人（ Ｐ＜ ０ ．０１） , Ｉ Ｇ Ｈ Ｄ 病人为（０ ．４ ±０ ．２） Ｒ Ｏ Ｄ,明显低于正常成人（ Ｐ＜ ０ ．０１） 。血清生长激素与 Ｉ Ｇ Ｆ Ｂ Ｐ３ 、胰岛素样生长因子 Ｉ与 Ｉ Ｇ Ｆ Ｂ Ｐ３ 均呈正相关（ Ｐ＜０ ．０５） 。结论　 Ｗｅｓｔｅｒｎ 印迹测定血清 Ｉ Ｇ Ｆ Ｂ Ｐ３ 正常值和病理值提示 Ｉ Ｇ Ｆ Ｂ Ｐ３ 浓度的变化与生长激素功能状态密切相关,并依赖 Ｇ Ｈ。     

脑梗塞患者炎性因子、血管活性肽含量变化及相互关系的研究

目的 探讨ＴＮＦ－α，ＩＬ－２和ＥＴ，ＣＧＲＰ的含量变化与脑梗塞发生的相互关系，方法 应用放射免疫分析法，检测了３４例脑梗塞患得及３０例正常人外用血和脑脊液中ＴＮＦ－αＩＬ－２，ＥＴ，ＣＧＲＰ含量。结果 脑梗塞患者血，脑脊液中ＴＮＦ－α，ＩＬ－２含量均显著高于对照组（Ｐ〈０．００１）。外周血ＥＴ含量显著高于对照组（Ｐ〈０．０５）。脑脊液中ＣＧＲＰ含量则明显低于对照组（Ｐ〈０．０５）。并且血中ＴＮＦ     

巨细胞病毒感染与动脉粥样硬化的临床研究

目的探讨人类巨细胞病毒（ＨＣＭＶ）感染、肿瘤坏死因子（ＴＮＦ）及血浆内皮素（ＥＴ）浓度与动脉粥样硬化的关系。方法采用间接免疫荧光技术测定急性心肌梗塞组（２０例）、冠状动脉狭窄组（２０例）及正常对照组（３０例）血清人类巨细胞病毒抗体，用放射免疫法测定血清ＴＮＦ及ＥＴ的浓度。结果急性心肌梗塞组ＨＣＭＶＩｇＭ阳性１４例（７０％），ＨＣＭＶＩｇＧ阳性２０例（１００％），ＨＣＭＶＩｇＭ、ＩｇＧ双阳性１４例（７０％）；冠状动脉狭窄组ＨＣＭＶＩｇＭ阳性１９例（９５％），ＨＣＭＶＩｇＧ阳性１９例（９５％），ＩｇＭ、ＩｇＧ双阳性１８例（９０％）；正常对照组ＨＣＭＶＩｇＭ阳性６例（２０％），ＨＣＭＶＩｇＧ阳性２６例（８２％），ＩｇＭ、ＩｇＧ双阳性６例（２０％），与正常对照组比较，差异有显著性（Ｐ＜０００１，Ｐ＜００５，Ｐ＜０００１）；冠心病急性心肌梗塞组、冠状动脉狭窄组与正常对照组相比，血清ＴＮＦ、血浆ＥＴ显著增高（Ｐ＜０００１）。结论患者的ＨＣＭＶ感染、内皮细胞受损和ＴＮＦ作用可能参与了冠心病发生发展的过程。     

运动对高脂饮食诱导肥胖大鼠过氧化物酶体增长因子活化受体-δ表达和胰岛素抵抗的影响

研究运动对高脂饮食诱导的肥胖大鼠肌肉和脂肪组织中过氧化物酶体增长因子活化受体-δ（PPAR-δ）表达的影响,并探讨其改善胰岛素抵抗的可能机制.方法 取体质量135～150 g的9周龄雄性Wistar大鼠80只,随机数字表法取其中60只6周时间饲以高脂饲料用于制作肥胖大鼠模型,另20只饲以普通饲料.将54只造模成功肥胖大鼠随机分为高脂饮食组（HFD）、高脂饮食同时运动组（E-HFD）、高脂饮食后运动组（HFD-E）,每组18只,同时从普通饲料饲养大鼠中随机选择16只作为正常饮食组（RD）.按文献标准对各组大鼠进行6周运动训练.检测比较各组游泳运动训练后体质量、肿瘤坏死因子（TNF）-α、瘦素、白细胞介素（IL）-1的水平以及空腹血糖、空腹胰岛素并计算胰岛素敏感指数（ISI）,采用实时定量聚合酶链反应（RT-PCR）检测肌肉和脂肪组织中PPAR-δ、葡萄糖转运蛋白（GLUT）-4、磷酸肌醇3激酶（PI3K）mRNA的表达,并采用Western blot法检测肌肉和脂肪组织中PPAR-δ蛋白的表达水平.组间数据比较采用双侧t检验.结果 HFD组ISI为1.13±0.21,相比HFD组,E-HFD组和HFD-E组的IS1分别提高了 71.1%和45.7%（分别为2.09±0.32和1.80±0.34）,而HFD-E组低于E-HFD组,差异均有统计学意义（均P＜0.05）.HFD组TNF-α水平为（101±24）ng/L,相比HFD组,E-HFD组和HFD-E组则分别下降了20.0%和9.2%[分别为（81±16）和（92±19）ng/L],差异均有统计学意义（P＜0.05）.与HFD组相比,E-HFD组和HFD-E组瘦素和IL-I水平均有显著下降（均P＜0.05）.与HFD组相比,E-HFD组和HFD-E组骨骼肌和脂肪中PPAR-δ、GLUT-4、PI3K mRNA的表达均显著升高,差异均有统计学意义（均P＜0.05）,且在E-HFD组变化尤为显著（均P＜0.01）.与HFD组相比,E-HFD组骨骼肌和脂肪组织中PPAR-δ蛋白表达分别升高了388.4%和203.2%（均P＜0.05）;HFD-E组骨骼肌和脂肪组织中PPAR-δ蛋白的表达则分别升高了272.9%和117.9%（均P＜0.05）.结论 运动降低了高脂饮食诱导的肥胖大鼠的血清脂肪因子瘦素、TNF-α和IL-1水平,改善了胰岛素抵抗,可能是通过上调肌肉和脂肪组织中PPAR-δ的表达发挥作用.     

Fish oil and argan oil intake differently modulate insulin resistance and glucose intolerance in a rat model of dietary-induced obesity

We investigated the potential metabolic benefits of fish oil (FO) or vegetable argan oil (AO) intake in a dietary model of obesity-linked insulin resistance. Rats were fed a standard chow diet (controls), a high-fat/high-sucrose (HFHS) diet, or an HFHS diet in which 6% of the fat was replaced by either FO or AO feeding, respectively. The HFHS diet increased adipose tissue weight and insulin resistance as revealed by increased fasting glucose and exaggerated glycemic and insulin responses to a glucose tolerance test (intraperitoneal glucose tolerance test). Fish oil feeding prevented fat accretion, reduced fasting glycemia, and normalized glycemic or insulin responses to intraperitoneal glucose tolerance test as compared with HFHS diet. Unlike FO consumption, AO intake failed to prevent obesity, yet restored fasting glycemia back to chow-fed control values. Insulin-induced phosphorylation of Akt and Erk in adipose tissues, skeletal muscles, and liver was greatly attenuated in HFHS rats as compared with chow-fed controls. High-fat/high-sucrose diet-induced insulin resistance was also confirmed in isolated hepatocytes. Fish oil intake prevented insulin resistance by improving or fully restoring insulin signaling responses in all tissues and isolated hepatocytes. Argan oil intake also improved insulin-dependent phosphorylations of Akt and Erk; and in adipose tissue, these responses were increased even beyond values observed in chow-fed controls. Taken together, these results strongly support the beneficial action of FO on diet-induced insulin resistance and glucose intolerance, an effect likely explained by the ability of FO to prevent HFHS-induced adiposity. Our data also show for the first time that AO can improve some of the metabolic and insulin signaling abnormalities associated with HFHS feeding.     

老龄大鼠脑缺血细胞因子含量的变化及其意义

目的　从细胞因子变化研究老龄大鼠脑缺血损伤的病理机制。方法　青年和老龄大鼠分为青年对照组、青年模型组和老龄对照组、老龄模型组 ,观察脑缺血模型IL 1、IL 8、TNF、TGFα和IGF 2含量的变化。结果　青年和老龄模型组血清IL 1、IL 8及血清与脑组织TNF含量分别较青年和老龄对照组增高 ,而TGFα和IGF 2降低 (P <0 0 5 ,P <0 0 1 ) ;老龄对照组血清TGFα和IGF 2含量低于青年对照组 (P <0 0 1 ,P <0 0 5) ;老龄模型组血清IL 8、TNF、TGFα和IGF 2含量较青年模型组差别显著 (P <0 0 5 ,P <0 0 1 )。结论　脑缺血损伤与IL 1、IL 8、TNF水平的增高及TGFα、IGF 2的降低有关 ,由于增龄改变使老年脑缺血损伤时上述细胞因子变化明显并具有一定的特点     

健脾理气化痰法针刺对高脂饲养胰岛素抵抗大鼠骨骼肌葡萄糖转运体4蛋白表达的影响

[目的]探讨健脾理气化痰法针刺对高脂饲养胰岛素抵抗大鼠骨骼肌葡萄糖转运体4（GLuT4）蛋白表达及胰岛素敏感性的影响。[方法]40只Wistar大鼠分别用高脂饲料、普通饲料喂养。经高胰岛素-正常葡萄糖钳夹术确定高脂饲养制备IR模型成功后,将模型大鼠随机分为模型组和电针组（取足三里、中脘、丰隆、关元穴）,普通饲料喂养组为正常组。治疗6周后,行腹腔糖耐量、腹腔胰岛素耐量实验测量各组大鼠血糖水平;治疗8周后,采用免疫组化法检测各组大鼠股四头肌GLUT4蛋白的表达。[结果]与模型组比较,电针组胰岛素降低血糖的效果显著增强（P〈o．01）;与模型组比较,电针组股四头肌GLUT4蛋白的表达水平增加（P〈o．05）。[结论]健脾理气化痰法针刺具有提高胰岛素敏感性的作用,并能显著提高股四头肌GLUT4蛋白的表达水平。     

不同目标血糖水平对脓毒症大鼠肿瘤坏死因子和内皮细胞特异性分子-1表达的影响

目的:探讨胰岛素控制不同目标血糖水平对脓毒症大鼠肿瘤坏死因子(TNF-α)、内皮细胞特异性分子(ESM-1)表达的影响以及对肺损伤的作用。方法:40只SD大鼠随机分为5组:假手术组(Sham组)、脓毒症组及血糖控制A组(4.4~6.1 mmol/L)、B组(6.2-8.3 mmol/L)、C组(8.4-10.0 mmol/L),各8只。盲肠结扎穿孔术后12 h处死,双抗夹心ELISA法检测血清TNF-α、ESM-1水平,光镜观察肺组织病理切片。结果:脓毒症组血清TNF-α、ESM-1的表达明显高于Sham组及各血糖控制组(均P0.05)。A组较B组和C组TNF-α、ESM-1的表达明显降低(均P0.05);B组低于C组(P0.05)。肺病理组织损伤评分脓毒症组均明显高于sham组及各控制组(均P0.05),A组较B组和C组明显降低(均P0.05)。结论:与6.2~8.3 mmol/L及8.4~10.0 mmol/L比较,血糖控制在4.4~6.1 mmol/L明显降低血中TNF-α、ESM-1的表达,且对脓毒症大鼠肺损伤保护作用最明显。     

Dietary fish oil reverses lipotoxicity, altered glucose metabolism, and nPKCepsilon translocation in the heart of dyslipemic insulin-resistant rats

The present study analyzes several markers of energy metabolism in the heart muscle of dyslipemic insulin-resistant rats fed a sucrose-rich diet (SRD, 62.5% wt/wt) for 8 months. It also explores the possible beneficial effects of dietary fish oil supplementation on cardiac lipids and glucose metabolism. With this purpose, male Wistar rats were fed an SRD for 6 months. Whereas half of the animals continued with the same diet for up to 8 months, the other half was fed an SRD in which fish oil (7% + 1% corn oil wt/wt) replaced corn oil (8% wt/wt) from months 6 to 8. The results were compared with rats fed a control diet (starch 62.5% wt/wt). The cardiac muscle of SRD-fed rats showed (1) a significant reduction (P < .05) in key enzymes activities and metabolites involved in glucose metabolism, accompanied by a significant (P < .05) increase of lipid storage (triglyceride, long-chain acyl coenzyme A, and diacylglycerol), and (2) a significant increase (P < .05) of nPKCepsilon protein mass expression in the membrane fraction without changes in the cPKCbetaII. Dietary fish oil, which reduces the availability of plasma lipid flux and normalizes glucose homeostasis, was able to reverse heart muscle lipotoxicity. Fish oil benefits key enzymes activities in glucose metabolism and normalizes glycogen and glucose-6-phosphate concentration, and the altered nPKCepsilon protein mass expression translocation in the heart of SRD-fed rats. Our findings suggest that manipulation of dietary fats may play a key role in the management of lipid disorders, offering a protection against the development of cardiovascular diseases.     

Increased leptin storage with altered leptin secretion from adipocytes of rats with sucrose-induced dyslipidemia and insulin resistance: effect of dietary fish oil

This study examined the effect of long-term feeding a high-sucrose diet (SRD) on the modulation of rat adipocyte's leptin secretion and storage. For this purpose, we analyzed (a) basal and insulin-stimulated leptin release and the role of isoproterenol and palmitate on insulin-stimulated leptin secretion, (b) the correlation between leptin and glycerol released, (c) the relationship between leptin contents and adiposity, and (d) the effect of fish oil (FO) administration on the above parameters. Wistar rats were fed an SRD for 6 months. Whereas half the animals continued with SRD up to month 8, the other half was fed an SRD in which FO partially replaced corn oil from months 6 to 8. Total leptin release was reduced both basally and under insulin stimulation in SRD-fed rats. However, the ratio of leptin released after hormone stimulation to basal leptin levels was similar in the 3 dietary groups. Isoproterenol inhibited insulin-stimulated leptin release in the 3 groups, but the percentage was lower in the SRD. Palmitic acid mimicked the effect of isoproterenol. Leptin release from adipocyte of SRD-fed rats negatively correlated with glycerol release. Leptin store increased in fat pads of SRD and positively correlated with adiposity. Fish oil reduced leptin content and fat pad hypertrophy, and normalized basal lipolysis, leptinemia, and glucose homeostasis. This suggests that enhanced lipolysis and altered insulin sensitivity could play a role in the decrease of leptin released in SRD-fed rats. This is consistent with the reversion of all the alterations after FO administration.     

成年期追赶生长对大鼠胰岛素敏感性与应激水平的影响

目的 观察成年期追赶生长对大鼠胰岛素敏感性和应激水平的影响,并探讨其胰岛素抵抗形成的可能机制。方法 将7周龄雄性SD大鼠分为6组（共2个时间点）,即4周时间点2组：热卡限制4周组(R4),正常饮食4周组(NC4)作为R4组对照;8周时间点4组：正常饮食追赶生长组(RN4)、高脂饮食追赶生长组(RH4)、持续高脂饮食8周组（HF8）、持续正常饮食8周组(NC8)。通过先热卡限制后恢复饮食的方法建立追赶生长大鼠模型。检测大鼠高胰岛素-正糖钳夹试验过程中葡萄糖输注率和骨骼肌2-脱氧葡萄糖摄取、胰岛素刺激后的骨骼肌胰岛素信号通路、血皮质酮、骨骼肌11β-羟类固醇脱氢酶1(11β-HSD1)表达水平。结果 热卡限制4周时,R4组大鼠血皮质酮和骨骼肌11β-HSD1 mRNA表达水平明显高于NC4组(P＜0.05),骨骼肌蛋白激酶B( Akt) Ser473磷酸化和糖摄取与NC4组相比差异无统计学意义。热卡限制后恢复饮食4周时,血皮质酮和骨骼肌11β-HSD1表达水平RN4组明显高于NC8组,RH4组明显高于NC8和HF8组,而骨骼肌Akt磷酸化和糖摄取RN4组明显低于NC8组,RH4组明显低于NC8组、HF8组和RN4组（均P＜0.05）。结论正常饮食和高脂饮食追赶生长大鼠均可导致整体和骨骼肌应激水平上调及胰岛素抵抗,尤以高脂饮食追赶生长大鼠更为明显。应激和饮食状况的交互作用可能是追赶生长胰岛素抵抗形成的重要原因。     

Skeletal muscle neuronal nitric oxide synthase micro protein is reduced in people with impaired glucose homeostasis and is not normalized by exercise training

Skeletal muscle inducible nitric oxide synthase (NOS) protein is greatly elevated in people with type 2 diabetes mellitus, whereas endothelial NOS is at normal levels. Diabetic rat studies suggest that skeletal muscle neuronal NOS (nNOS) micro protein expression may be reduced in human insulin resistance. The aim of this study was to determine whether skeletal muscle nNOSmicro protein expression is reduced in people with impaired glucose homeostasis and whether exercise training increases nNOSmicro protein expression in these individuals because exercise training increases skeletal muscle nNOSmicro protein in rats. Seven people with type 2 diabetes mellitus or prediabetes (impaired fasting glucose and/or impaired glucose tolerance) and 7 matched (sex, age, fitness, body mass index, blood pressure, lipid profile) healthy controls aged 36 to 60 years participated in this study. Vastus lateralis muscle biopsies for nNOSmicro protein determination were obtained, aerobic fitness was measured (peak pulmonary oxygen uptake [Vo(2) peak]), and glucose tolerance and insulin homeostasis were assessed before and after 1 and 4 weeks of cycling exercise training (60% Vo(2) peak, 50 minutes x 5 d wk(-1)). Skeletal muscle nNOSmicro protein was significantly lower (by 32%) in subjects with type 2 diabetes mellitus or prediabetes compared with that in controls before training (17.7 +/- 1.2 vs 26.2 +/- 3.4 arbitrary units, P < .05). The Vo(2) peak and indicators of insulin sensitivity improved with exercise training in both groups (P < .05), but there was no effect of exercise training on skeletal muscle nNOSmicro protein in either group. In conclusion, individuals with impaired glucose homeostasis have reduced skeletal muscle nNOSmicro protein content. However, because exercise training improves insulin sensitivity without influencing skeletal muscle nNOSmicro protein expression, it seems that changes in skeletal muscle nNOSmicro protein are not central to the control of insulin sensitivity in humans and therefore may be a consequence rather than a cause of diabetes.     

Insulin-nonspecific reduction in skeletal muscle glucose transport in high-fat-fed rats

High-fat feeding diminishes insulin-stimulated glucose transport in skeletal muscle. However, conflicting results are reported regarding whether phosphatidylinositol (PI)-3 kinase-independent glucose transport is also impaired in insulin-resistant high-fat-fed rodents. The aim of the present study was to study whether non-insulin-dependent mechanisms for stimulation of glucose transport are defective in skeletal muscle from high-fat-fed rats. Rats were fed normal chow diet or high-fat diet for 4 weeks and isolated epitrochlearis muscles were used for measuring glucose transport. Insulin-stimulated glucose transport was significantly lower in rats fed the high-fat diet compared with chow-fed rats (P < .05). Hypoxia-stimulated glucose transport was also reduced in high-fat-fed rats (P < .05). Nevertheless, hypoxia-stimulated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation (Thr172) level was not affected by high-fat feeding. Glucose transport by sodium nitroprusside stimulation was reduced in high-fat-fed rats (P < .05). Protein content of glucose transporter (GLUT)-4 and AMPK-alpha, and glycogen content were comparable between both groups. Our findings provide evidence that high-fat feeding can affect not only insulin but also non-insulin-stimulated glucose transport. A putative defect in common steps in glucose transport may play a role to account for impaired insulin-stimulated glucose transport in rats fed a high-fat diet.