慢性间歇低氧对大鼠血压和交感神经兴奋性的影响

目的 通过观察不同程度慢性间歇低氧(chronic intermittent hypoxia,CIH)作用下大鼠血压与交感神经活性水平动态变化,探讨CIH对血压及交感神经活性的影响及血压与交感神经活性之间的相关性,并明确CIH诱发高血压发病的机制.方法 168只雄性6周龄Wistar大鼠,体重160 ～ 180 g,采用随机数字表法分为非暴露组(UD)、重度间歇低氧组(IH1)、中度间歇低氧组(IH2)、轻度间歇低氧组(IH3)、持续低氧组(CH)及对照组,分别给予不同程度和频率的低氧环境.UD组8只大鼠于实验前处死,其余各实验组每组32只大鼠,分别于2、4、6、8周时随机抽取8只处死,留取静脉血抗凝离心后- 80℃保存血浆,并于实验前、实验结束后分别测定动脉收缩压,实验结束后测定血浆中去甲肾上腺素(norepinephrine,NE).结果 各组大鼠实验前收缩压差异无统计学意义(F=0.008,P＞0.05),随着实验时间延长,各间歇低氧组大鼠收缩压逐渐升高,4周开始明显高于UD组、对照组及CH组(均P＜0.05)且血压水平与低氧程度正相关(F =9.844,P＜0.01),IH1组明显高于IH3组(P＜0.05),而对照组和CH组无明显改变.各间歇低氧组大鼠血浆NE随实验时间延长而逐渐升高,8周时明显高于UD组、SC组及CH组(均P＜0.05或P＜0.01),且NE水平与低氧程度正相关(F=11.537,P＜0.01),IH1组明显高于IH3组(P＜0.05),SC组和CH组大鼠血浆NE变化不显著.大鼠血浆NE与血压呈显著正相关(r=0.538,P＜0.01).结论 CIH作用可以引起大鼠血压增高和交感活性增强且存在明显的低氧程度依赖性和时间过程规律性,推测CIH引起大鼠血压增高可能与交感活性增强相关.     

慢性间歇性缺氧对大鼠胸骨舌骨肌收缩能力及疲劳指数的影响

目的 探讨慢性间歇性缺氧对大鼠上气道扩张肌即胸骨舌骨肌收缩性能的影响。方法 取健康雄性SD大鼠12只，随机分为正常对照组和慢性间歇性缺氧组，采用电刺激法，测定等长收缩胸骨舌骨肌肌条在不同条件下收缩性能及疲劳指数的变化。结果 慢性间歇性缺氧可造成大鼠胸骨舌骨肌在10和20Hz刺激下肌张力明显较对照组下降，两者比较差异有显著性；其肌肉的颤搐和强直性张力、颤搐／强直性张力比虽有所下降，但差异无显著性；此外，慢性间歇缺氧能显著增加胸骨舌骨肌的疲劳度。结论 慢性间歇性缺氧能够降低上气道扩张肌的张力，增加上气道肌的疲劳，使上气道抗疲劳能力下降，从而使其在抵抗上气道在吸气时负压的作用下降，可能参与了睡眠呼吸暂停的发病过程，加重或诱发呼吸暂停。     

慢性间断缺氧小鼠缺氧诱导因子1α的研究

目的　探索睡眠呼吸暂停综合征(SAS)的慢性间断性缺氧(CIH)对心血管损害的可能机制。方法　制作CIH小鼠模型。将30只ICR小鼠均分为实验组、空气模拟对照组及空白对照组。免疫组织化学方法检测实验小鼠心肌细胞缺氧诱导因子1α(HIF1α)及诱导型一氧化氮合成酶(NOS2)的表达。酶联免疫吸附测定(ELISA)方法检测小鼠血浆血管内皮生长因子(VEGF)及内皮素1(ET1)的浓度。结果　实验组心肌细胞HIF1α表达高于空白对照组(t=354,P<005)及空气模拟对照组(t=292,P<005);空白对照组HIF1α表达与空气模拟对照组比较差异无统计学意义(P>005)。实验组血浆VEGF浓度[(957±141)ng/ml]高于空白对照组[(810±062)ng/ml,q=427,P<005]及空气模拟对照组[(832±099)ng/ml,q=364,P<005];空白对照组血浆VEGF浓度与空气模拟对照组比较差异无统计学意义(P>005)。实验组血浆ET1浓度[(331±081)ng/ml]高于空白对照组[(250±072)ng/ml,q=364,P<005];空气模拟对照组血浆ET1浓度[(269±043)ng/ml]与实验组及空白对照组[(331±081)、(250±072)ng/ml]比较差异均无统计学意义(P均>005)。小鼠心肌细胞NOS2表达在各组间比较差异均无统计学意义(P均>005)。结论　CIH可引起小鼠HIF1α表达增加,并可促进HIF1α目的基因产物VEGF、ET1的表达。这可能     

The effects of in utero and lactational exposure to chloroform on postnatal growth and glucose tolerance in male Wistar rats

Water chlorination results in the formation of trihalomethanes (THMs) including chloroform. In human studies, fetal growth restriction has been associated with exposure to THMs during pregnancy and impaired fetal growth has been associated with an increased risk of type 2 diabetes. Therefore, the objective of this study was to determine the effect of in utero and lactational exposure to chloroform on birthweight and postnatal indicators of type 2 diabetes. Female Wistar rats were given chloroform (0 μg/L, 75 μg/L) in their drinking water for 2 wk prior to mating until parturition (in utero exposure only) or until weaning (in utero + lactational exposure). At postnatal d 1 (PND1) pups of dams exposed to chloroform had significantly higher serum glucose levels and lower insulin levels, but this effect was not due to β-cell depletion in the neonatal pancreas. Glucose homeostasis in response to a glucose challenge was not changed by chloroform treatment. Chloroform exposure did not affect birthweight; however, offspring of dams exposed to chloroform had significantly impaired postnatal growth. Although fetal and neonatal exposure to chloroform did not elicit physiological changes associated with the onset of type 2 diabetes, there were physiological changes resulting in impaired postnatal growth.     

慢性间歇低氧对大鼠糖代谢及肝脏 TRB3、P-AKT 表达的影响

目的：通过建立慢性间歇低氧(chronic intermittent hypoxia,CIH)大鼠模型,观察CIH 对大鼠糖代谢的影响以及肝脏胰岛素相关信号通路 Tribbles 同源蛋白3(TRB3)、磷酸化蛋白激酶 B (P-AKT)的变化。方法将40只健康雄性 SD 大鼠随机分为5组,每组8只。正常对照组(NC组)、慢性间歇 低 氧 2 周 组(CIH2组)、慢 性 间 歇 低 氧 4 周 组(CIH4组)、慢性间歇低氧6周组(CIH6组)、慢性间歇低氧8周组(CIH8组),实验组每天给予8 h 间歇低氧处理。实验结束后检测5组大鼠空腹血糖,采用酶联免疫吸附试验(ELISA)检测空腹胰岛素,用稳态模型胰岛素抵抗指数(HOMA-IR)系统评价胰岛素抵抗。采用 HE 染色观察各组肝脏组织形态变化,SABC 法免疫组织化学试剂盒检测大鼠肝细胞 TRB3蛋白以及胰岛素信号通路中关键激酶蛋白激酶 B (AKT)磷酸化水平蛋白的表达,以平均灰度值表示 TRB3、P-AKT 的蛋白表达量。结果随着间歇低氧暴露时间延长,各组与 NC 组比较,其空腹血糖水平(F =116.185,P <0.05)、胰岛素水平(F =45.189,P <0.05)、HOMA-IR (F =110.876,P <0.05)、TRB3蛋白表达水平(F =11 5.253,P <0.05)升高,而 P-AKT 蛋 白 表 达 水 平(F =99.553,P <0.05) 降 低,且以 CIH8组 最 为 显 著 (P <0.05)。Pearson 相关分析显示： HMOA-IR 与 TRB3平均灰度值呈负相关(r =-0.828,P <0.05),与P-AKT平均灰度值呈正相关(r =0.903,P <0.05)。结论 CIH 可导致大鼠肝细胞受损,糖代谢异常,发生胰岛素抵抗,并随着间歇低氧暴露时间的延长,胰岛素抵抗程度加重。CIH 使肝脏中 TRB3蛋白表达增加,P-AKT 显著降低,且与 HOMA-IR 具有明显的相关性,TRB3的激活可能在 CIH 所致的糖代谢异常中起重要作用。     

The effect of early postnatal hypoxia on the regional cerebral utilization of glucose in adult rats

The purpose of this study was to establish if there are any later changes in the local cerebral energy metabolism after exposing 1-day-old rats for 5 days (10 hr daily) to hypobaric hypoxia (pO ₂=10.5 kPa). For this study the 2-[¹⁴C]deoxyglucose method for the determination of the regional utilization of glucose in the rat brain was employed. The results, obtained in 41 cerebral structures, show that rats subjected to an early postnatal hypoxia exhibit a significant decrease (–41%) 3 months later in the utilization of glucose in the CA₃ area of the hippocampus. This finding is a new one in the chain of several biochemical and behavioral changes observed in this experimental model. It is suggested that this finding could be useful in the search for a new therapeutic agent eventually able to alleviate the consequences of perinatal hypoxia.     

Cardioprotective effects of melatonin against myocardial injuries induced by chronic intermittent hypoxia in rats

Obstructive sleep apnea (OSA) associated with chronic intermittent hypoxia (CIH) increases the morbidity and mortality of ischemic heart disease in patients. Yet, there is a paucity of preventive measures targeting the pathogenesis of CIH‐induced myocardial injury. We examined the cardioprotective effect of melatonin against the inflammation, fibrosis and the deteriorated sarcoplasmic reticulum (SR) Ca²⁺ homeostasis, and ischemia/reperfusion (I/R)‐induced injury exacerbated by CIH. Adult male Sprague Dawley rats that had received a daily injection of melatonin (10 mg/kg) or vehicle were exposed to CIH treatment mimicking a severe OSA condition for 4 wk. Systolic pressure, heart weights, and malondialdehyde were significantly increased in hypoxic rats but not in the melatonin‐treated group, when compared with the normoxic control. Levels of the expression of inflammatory cytokines (TNF‐α, IL‐6, and COX‐2) and fibrotic markers (PC1 and TGF‐β) were significantly elevated in the hypoxic group but were normalized by melatonin. Additionally, infarct size of isolated hearts with regional I/R was substantial in the hypoxic group treated with vehicle but not in the melatonin‐treated group. Moreover, melatonin treatment mitigated the SR‐Ca²⁺ homeostasis in the cardiomyocyte during I/R with (i) Ca²⁺ overloading, (ii) decreased SR‐Ca²⁺ content, (iii) lowered expression and activity of Ca²⁺‐handling proteins (SERCA2a and NCX1),and (iv) decreased expressions of CAMKII and phosphorylated eNOS^ser1177. Furthermore, melatonin ameliorated the level of expression of antioxidant enzymes (CAT and MnSOD) and NADPH oxidase (p22 and NOX2). Results support a prophylactic usage of melatonin in OSA patients, which protects against CIH‐induced myocardial inflammation and fibrosis with impaired SR‐Ca²⁺ handling and exacerbated I/R injury.     

间歇低氧对大鼠血管内皮硫氧还蛋白的影响

目的 通过测定睡眠呼吸暂停模式间歇低氧大鼠血管内皮硫氧还蛋白(thioredoxin,TRX)mRNA的表达水平,进一步探讨氧化应激在阻塞性睡眠呼吸暂停综合征导致高血压发生机制中的具体作用.方法 160只成年雄性Wistar大鼠随机分为5组:5%间歇低氧组,7.5%间歇低氧组,10%间歇低氧组,10%持续低氧对照组和常...     

慢性间歇低氧对大鼠肝细胞IRS-2、 FoxO1表达的影响

目的 观察慢性间歇低氧条件下,大鼠肝细胞形态学变化及胰岛素受体底物-2 (IRS-2)、叉头框蛋白O1(FoxO1)的蛋白表达,并探讨IRS-2、FoxO1与胰岛素抵抗的相关性.方法 取24只6周龄健康雄性Sprauge-Dawley大鼠,采用随机数字表法分为正常对照组(NC组)、慢性间歇低氧4周组(CIH4组)、慢性间歇低氧8周组(CIH8组),每组8只.CIH4组和CIH8组暴露于间歇低氧舱内:最低氧浓度6％ ～ 8％,持续时间8 h/d.NC组无间歇低氧暴露正常饲养,CIH4组、CIH8组和NC组分别于第4周、第8周及第8周禁食12 h后测定空腹血糖、空腹胰岛素水平,并采用稳态模型评估-胰岛素抵抗指数(HOMA-IR)和胰岛素敏感性指数(ISI)评价胰岛素抵抗,对肝组织行HE染色观察形态学变化,采用免疫组织化学方法测定肝细胞IRS-2、FoxO1蛋白表达,以平均灰度值表示其蛋白表达量,二者成反比关系.结果 与NC组相比,CIH4组、CIH8组空腹血糖、胰岛素、HOMA-IR升高,ISI降低,且CIH8组更为显著,差异有统计学意义(F=50.23 ～90.26,P均＜0.05).与NC组相比,CIH4组与CIH8组IRS-2蛋白表达降低,FoxO1蛋白表达增高且在核内重新分布,CIH8组更为显著,差异有统计学意义(F=69.46,618.94,P均＜0.05).Pearson相关分析显示:HMOA-IR与IRS-2平均灰度值呈正相关(r=0.857,P＜0.05),与FoxO1平均灰度值呈负相关(r=-0.926,P＜0.05),ISI与IRS-2平均灰度值呈负相关(r=-0.823,P＜0.05),与FoxO1平均灰度值呈正相关(r=0.848,P＜0.05).结论 慢性间歇低氧条件下,大鼠肝细胞受损并发生胰岛素抵抗,同时IRS-2和FoxO1蛋白表达异常,且随暴露时间延长肝细胞损伤程度及胰岛素抵抗程度均逐渐加重.     

慢性间歇低氧对大鼠血管内皮功能的影响以及抗氧化剂干预作用

目的 通过测定血清中血管活性物质,探讨慢性间歇低氧(CIH)对大鼠血管内皮功能的影响,以及抗氧化剂4-羟基-2,2,6,6四甲基哌啶(Tempol)的防治作用.方法 将48只Wistar雄性大鼠随机分为6组,每组8只,包括常氧对照组(NC组)、间歇低氧组(IH组)和4组间歇低氧Tempol干预及其对照组:IHT1组、IHT2组、IHN1组、IHN2组.IHT1、IHT2组分别为实验前和实验后第28天给予10％ Tempol100mg· kg-1·d-1腹腔注射,IHN1、IHN2组于相同时间给予等量生理盐水腹腔注射.结果 IHT2组与IHN2组比较,ET-1水平显著降低(P＜0.05),NO、eNOS水平升高(P值均＜0.05);但ET-1水平仍高于NC组(P＜0.01),NO、eNOS较其降低(P值均＜0.01).IHT1组ET-1水平低于IHT2组(P＜0.01),NO、eNOS水平较其升高(P值均＜0.01);各指标与NC组差异无统计学意义.IH组与IHN1组、IHN2组相比,各指标差异均无统计学意义.结论 CIH可能通过氧化应激引起血清ET-1、NO含量失衡,导致内皮功能障碍.抗氧化剂Tempol可减轻血管内皮氧化应激损伤,在改善血管内皮功能方面具有一定的意义.     

慢性间歇低氧对大鼠颏舌肌细胞线粒体功能的影响及脂联素的干预作用

目的 探讨慢性间歇低氧(CIH)对大鼠颏舌肌细胞线粒体功能的影响及脂联素干预作用.方法 健康雄性Wistar大鼠39只,采用随机数字表法分成健康对照(NC)组、CIH组、CIH脂联素干预组(CIH+Ad组),每组13只.NC组大鼠呼吸正常空气,CIH组与CIH+Ad组均接受CIH环境(CIH 8 h/d,共5周),CIH+Ad组加用经静脉脂联素注射10 μg/次,2次/周,共5周.于实验终止(第35天)时测定并比较各组大鼠血清脂联素浓度、颏舌肌线粒体膜电位、线粒体复合物Ⅰ活性、线粒体复合物Ⅳ活性.结果 CIH组血清脂联素浓度明显低于NC组[(1108±112)ng/ml,(2241±121)ng/ml,P＜0.01];CIH+Ad组高于CIH组[(1889±119)ng/ml]但低于NC组[(2241±121)ng/ml,均P＜0.01].CIH组颏舌肌线粒体膜电位相对值(1.82±0.11)明显低于NC组(2.09±0.14,P＜0.01),CIH+Ad组(1.98±0.09)较CIH组略高但低于NC组,差异均有统计学差异(均P＜0.05).CIH组线粒体复合物Ⅰ、Ⅳ浓度[(35.68±1.73)μmol·min-1·mg-1,(2.37±0.11)nmol·min-1·mg-1]最低,CIH+Ad组[(37.18±1.95)μmol·min-1·mg-1,(2.49±0.09)nmol·min-1·mg-1]及NC组[(39.02±1.38)μmol·min-1·mg-1,(2.81±0.12)nmol·min-1·mg-1]依次增高.NC组与CIH组比较差异有统计学意义(P＜0.01),CIH+Ad组与CIH组和NC组比较差异有统计学意义(均P＜0.05).结论 CIH可致大鼠血清脂联素水平降低,并能显著损伤颏舌肌细胞线粒体功能,补充外源性脂联素能部分改善CIH对大鼠颏舌肌细胞线粒体功能的损伤,提示低脂联素血症可能参与CIH导致的颏舌肌能量代谢障碍.

Abstract：

Objective To investigate the effect of chronic intermittent hypoxia (CIH) on mitochondrial function in genioglossus cells of rats and intervention role of adiponectin (Ad). Methods Thirty-nine healthy male Wistar rats were randomly divided into 3 groups, normal control (NC) group, CIH group and CIH + Ad group with 13 rats in each. Rats in NC group were kept breathing normal air, while rats in both CIH and CIH + Ad groups experienced the same CIH environment ( CIH 8 h/day for successive 5 weeks). However, rats in CIH + Ad group was given intravenous Ad supplement at the dosage of 10 μg,twice a week for sucessive 5 weeks. At the end of experiment ( day 35 ), the levels of plasma adiponectin,mitochondrial membrane potential activities of respiratory chain complexes Ⅰ and Ⅳ in mitochondrion of genioglossus cells were compared among different groups. Results Serum Ad level was significantly lower in CIH group than that in NC group [(1108 ± 112) ng/ml vs (2241 ± 121) ng/ml, P＜0.01 ]. Serum Ad level in CIH + Ad group [ ( 1889 ± 119) ng/ml] was significantly higher than that in NC group but lower than that in CIH group ( all P ＜ 0. 01 ). Mitochondrial membrane potential was significantly lower in CIH group than that in NC group [ ( 1.82 ± 0. 11 ) vs (2. 09 ± 0. 14), P ＜ 0. 01 ]. Mitochondrial membrane potential in CIH + Ad group ( 1.98 ± 0. 09) was higher than that in CIH group but lower than that in NC group ( all P ＜ 0. 05 ). The concentrations of mitochondrial respiratory chain complexes Ⅰ and Ⅳ in CIH group ( 35.68 ± 1.73 ) μmol · min - 1 · mg- 1 and (2. 37 ± 0. 11 ) nmol · min - 1 ·mg - 1, respectively) were the lowest but became higher from CIH + Ad group [ (37. 18 ± 1.95) μ mol· min-1 · mg-1 and (2. 49 ±0.09) nmol · min-1 ·mg-1 ,respectively] to NC group (39.02 ± 1.38) μmol · min-1 · mg-1 and (2. 81±0. 12) nmol · min-1 ·mg-1 ,respectively), with a significant difference between NC and CIH groups ( P ＜ 0. 01 ), between CIH + Ad and CIH groups ( P ＜ 0. 05 ), as well as between CIH + Ad and NC groups (P ＜ 0. 05 ). Conclusion CIH could lead to hypoadiponectinemia and impaired mitochondrial function in genioglossus cells of rats. Since such changes could be partially improved by supplement of adiponectin, it was suggested that hypoadiponectinemia might be involved in CIH-induced impairment of genioglossus energy metabolism.     

慢性间歇低氧致去卵巢小鼠动脉损伤及其与硫氧还蛋白-1的关系

目的 研究雌激素在慢性间歇低氧致血管损伤中的保护作用及其与硫氧还蛋白-1( Trx-1)的关系.方法 36只成熟雌性C57/BL6J小鼠随机分为去卵巢间歇低氧(OVI)组、假手术间歇低氧(SOI)组以及对照组;前两组给予间歇低氧,而对照组间歇给予空气.28 d后,观察小鼠子宫的大小与形态并称重;主动脉弓石蜡切片进行HE染色,光学显微镜观察血管形态并测量血管壁内中膜厚度(IMT);石蜡切片行免疫组化检测Trx-1蛋白表达水平;实时荧光定量PCR检测Trx-1的mRNA相对表达量.结果 HE可见对照组主动脉弓内皮光滑,平滑肌细胞排列较整齐,未见明显异常改变;SOI组可见内皮欠连续,局灶内皮细胞聚集,主动脉弓平滑肌纤维细胞排列紊乱、肥大以及平滑肌纤维样变;OVI组除可见SOI组小鼠的上述改变加重外,另可见血管局灶内膜明显增生以及外膜增厚等改变.对照组、SOI组及OVI组的IMT分别为(38.34±1.01) μm、(50.65±2.09)μm及(64.80+4.31)μm,三组间两两比较差异具有统计学意义(P＜0.01).SOI组(8.59±0.83)及OVI组(5.14±1.01)小鼠胸主动脉Trx-1mRNA相对表达量显著高于对照组(0.18±0.13),差异具有显著统计学意义(P＜0.001);对照组、SOI组及OVI组小鼠主动脉弓Trx-1蛋白表达的累积光密度分别为(0.84±0.10)×103、(6.60±0.45)×103及(2.76±0.28)×103,三组间两两比较差异均具有显著统计学意义(P＜0.001).结论 CIH可导致主动脉弓血管壁形态改变,去卵巢可加重CIH所致主动脉弓的损害,而Trx-1蛋白表达的降低可能参与了此过程.     

慢性间歇低氧对大鼠肾脏组织细胞形态和超微结构的影响

目的 探讨慢性间歇低氧( CIH)对肾脏组织细胞形态和超微结构的影响及其意义.方法 采用自制的CIH动物舱,通过控制程序调节舱内氧气、氮气的输入流量,使得每1次缺氧循环时间为1 min,氧气浓度循环于7％～21％之间.将18只大鼠随机分成2组,每组9只,分别为对照组和CIH组.将CIH组置于动物舱给予间歇缺氧,每天8h,持续35 d.对照组动物舱内输入空气,其余条件同CIH组.HE染色观察肾脏组织细胞形态,透射电镜观察肾近曲小管上皮细胞超微结构.结果 HE染色示对照组肾脏组织形态基本正常,CIH组肾小球高度肿胀,肾球囊狭窄,近曲小管上皮细胞高度肿胀,管腔狭窄.透射电镜观察发现对照组肾脏超微结构基本正常,CIH组肾近曲小管上皮细胞出现空泡变性、核膜肿胀和线粒体肿胀.结论 CIH导致肾脏组织细胞水肿变性和超微结构异常,可能与OSAHS引起肾脏损害有关.     

Distribution of intracellular and secreted surfactant during postnatal rat lung development

Pulmonary surfactant prevents alveolar collapse via reduction of surface tension. In contrast to human neonates, rats are born with saccular lungs. Therefore, rat lungs serve as a model for investigation of the surfactant system during postnatal alveolar formation. We hypothesized that this process is associated with characteristic structural and biochemical surfactant alterations. We aimed to discriminate changes related to alveolarization from those being either invariable or follow continuous patterns of postnatal changes. Secreted active (mainly tubular myelin (tm)) and inactive (unilamellar vesicles (ulv)) surfactant subtypes as well as intracellular surfactant (lamellar bodies (lb)) in type II pneumocytes (PNII) were quantified before (day (d) 1), during (d 7), at the end of alveolarization (d 14), and after completion of lung maturation (d 42) using electron microscopic methods supplemented by biochemical analyses (phospholipid quantification, immunoblotting for SP-A). Immunoelectron microscopy determined the localization of surfactant protein A (SP-A). (1) At d 1 secreted surfactant was increased relative to d 7-42 and then decreased significantly. (2) Air spaces of neonatal lungs comprised lower fractions of tm and increased ulv, which correlated with low SP-A concentrations in lung lavage fluid (LLF) and increased respiratory rates, respectively. (3) Alveolarization (d 7-14) was associated with decreasing PNII size although volume and sizes of Lb continuously increased. (4) The volume fractions of Lb correlated well with the pool sizes of phospholipids in lavaged lungs. Our study emphasizes differential patterns of developmental changes of the surfactant system relative to postnatal alveolarization.     

交感神经兴奋在慢性间歇性低氧引起高血压发生过程中的作用

交感神经活性增强在阻塞性睡眠呼吸暂停引起的高血压及其他心血管疾病发生过程中起到重要作用.阻塞性睡眠呼吸暂停(obstructive sleep apnea,OSA)最为明显的特征就是夜间反复的间歇 性低氧,这种间歇性低氧状态对于交感神经激活及血压升高显得尤为重要.以下就OSA相关性间歇性低氧引起的交感神经系统激活以及其...     

间歇低氧对人脐静脉内皮细胞中内皮素的影响

目的通过建立间歇低氧细胞模型,测定不同低氧模式下人脐静脉内皮细胞中内皮素(endothelin,ET)含量的变化,以进一步探讨ET在细胞水平对间歇低氧在阻塞性睡眠呼吸暂停综合征合并高血压患者中的作用.方法采用人脐静脉内皮细胞可传代细胞株ECV304细胞系,暴露于不同低氧条件,暴露完成后采用双抗夹心酶联免疫吸附法(ELISA法)测定培养基中ET浓度.结果间歇低氧组ET浓度[(12.86±6.68)pg/mL]与间歇正常氧组[(3.29±0.88)pg/mL]及空白对照组[(4.67±1.22)pg/mL]间差异有统计学意义(F=13.687,P<0.05).其中,间歇低氧组高于间歇正常氧组(P<0.05)及空白对照组(P<0.05),而间歇正常氧组及空白对照组间差异无统计学意义(P>0.05).相同累加低氧时间及程度的间歇低氧组ET浓度显著高于持续低氧组[(7.07±1.00)pg/mL](P<0.05).结论间歇低氧可引起ET水平升高,提示ET在间歇低氧合并高血压中可能起重要作用.     

间歇性低氧对大鼠白细胞介素-1水平的影响

目的探讨间歇性低氧对大鼠血浆中IL-1的影响。方法借助OSAS大鼠动物模型,模拟OSAS患者夜间反复发生的间歇性低氧的病理生理改变,观察大鼠血浆中IL-1水平的变化。结果 OSAS大鼠血浆中IL-1β水平较正常对照组显著增高。结论反复间歇性低氧可能通过促进IL-1的释放,炎症反应的发生。     

慢性间歇低氧老龄大鼠脑血管内皮功能的研究

目的 探讨慢性间歇低氧(CIH)对老龄鼠脑血管及内皮素-1(ET-1)、一氧化氮(NO)、血管内皮生长因子(VEGF)表达的影响.方法 应用间歇低氧处理方式建立CIH老龄大鼠实验模型,实验3、6、9周后,检测血浆ET-1、NO和VEGF的含量;观察脑血管病理变化与脑组织中小动脉血管壁厚度与外径之比(WT%)与VEGF蛋白的表达.结果 CIH组血ET-1、VEGF表达均增加,NO表达减弱,从第3周ET-1含量较空白对照(UC)组增高(t=2.47,P<0.05),VEGF含量较空白对照(UC)组升高(t=2.38,P<0.05),NO含量较UC组降低(t=2.39,P<0.05).VEGF水平与间歇低氧时间呈正相关,第9周[(171.1±13.5)pg/ml]表达最强,与第3周[(129.3±12.3)pg/ml]比较升高明显(t=2.38,P<0.05),较UC组[(109.8±8.6)pg/ml]增高(t=3.46,P<0.01).光镜下UC组脑血管未见明显的病理变化,CIH组可见脑细胞水肿和血管增生.CIH组大鼠脑小动脉WT%改变从第3周即强于UC组(t=2.34,P<0.05),脑组织VEGF的表达在CIH组各时间段均显著高于UC组(t=2.37,P<0.05),随着CIH作用时间的累积,脑组织VEGF和脑小动脉WT%改变均有加重的趋势,第9周明显高于第3周(t=2.32和t=2.35,均P<0.05).结论 CIH可诱导老龄大鼠ET-1、VEGF表达增强,NO水平下降,导致脑细胞肿胀,小动脉管壁增厚,管腔狭窄,提示纠正VEGF、ET-1/NO的表达紊乱应成为OSAS综合防治的一个重要方面.     

ACTH and growth hormone in myocardial LDH adaptation to hypoxia in rats

The role of hypophysis in cardiac growth, and in myocardial lactic dehydrogenase (LDH) isoenzyme adaptations to hypobaric hypoxia (9.5% O₂) during 3 weeks was studied in four groups of hypophysectomized rats: one group received no hormone, and the second, third, and fourth groups received, respectively, growth hormone, ACTH, and growth hormone+ACTH. One hypophysectomized and one non-surgical group maintained at sea-level and one non-surgical group exposed to hypoxia served as controls. Exposure of hypophysectomized rats to hypoxia produced a proportional loss of body and heart weight with an equal decrease in both LDH subunits, H (heart) and M (muscle). Growth hormone and/or ACTH did not reverse cardiac atrophy. ACTH given alone or with growth hormone enhanced M-subunit synthesis (2-to 4-fold) and corrected the H/M ratio to the level of the non-surgical controls exposed to hypoxia, but at the expense of a lower total level of LDH.The adaptative changes in LDH isoenzymes induced by hypoxia could be abolished with hypophysectomy, and partly restored by giving growth hormone and ACTH, but this restoration was not coupled with cardiac growth.This study was done at The Wihuri Research Institute, Helsinki, Finland