Kv通道亚型在15-HETE收缩肺动脉过程中的作用

目的从组织功能及细胞分子水平研究电压门控型钾通道(Kv通道)亚型在15-羟化二十碳四烯酸(15-HETE)致大鼠肺动脉收缩过程中的作用。方法采用组织浴槽血管环法，使用Kv通道阻断剂，确定受15-HETE调控大鼠肺动脉平滑肌细胞(PASMCs)膜上Kv亚型；使用RT-PCR和Western blotting技术观察受15-HETE调控PASMCs 膜上Kv亚型。结果阻断Kv1.1，Kv1.2，Kv1.3和Kv1.6通道并不影响15-HETE诱导肺动脉血管收缩；15-HETE不影响PASMCs膜上Kv1.1和Kv1.2通道蛋白质表达；15-HETE下调PASMCs膜上Kv1.5和Kv2.1通道mRNA和蛋白质表达。结论缺氧可能是通过15-HETE这一介导因子抑制Kv1.5和Kv2.1通道，减少PASMCs膜上功能性Kv1.5和Kv2.1通道数量，导致PASMCs收缩。     

Garlic elicits a nitric oxide-dependent relaxation and inhibits hypoxic pulmonary vasoconstriction in rats

1. The aims of the present study were to determine the characteristics of garlic extract-induced relaxation in rat isolated pulmonary arteries, its susceptibility to changes in oxygen tension and its protective effect against hypoxic pulmonary vasoconstriction. 2. In normoxia, garlic extract (3-500 microg/mL) produced a dose- and nitric oxide (NO)-dependent relaxation. Following 60 min hypoxia, maximum garlic relaxation was reduced compared with control (mean (-SEM) -86 +/- 3 vs-69 +/- 2% of phenylephrine (PE) precontraction, respectively), but recovered after 60 min reoxygenation (-85 +/- 3% PE precontraction). 3. Acetylcholine (0.1 micromol/L)-induced NO-dependent relaxation was reduced from a control value of -76 +/- 1% to -46 +/- 4% during hypoxia and was further reduced to -35 +/- 2 % after reoxygenation. 4. In endothelium-intact arteries, hypoxic exposure resulted in a triphasic response: early transient contraction (+24 +/- 4%), followed by transient relaxation (-37 +/- 7%) and then sustained contraction (+62 +/- 5%). 5. Pretreatment with NG-nitro-L-arginine methyl ester abolished the early transient contraction, moderately attenuated the sustained contraction and had no effect on the transient relaxation. Mechanical endothelial disruption inhibited all hypoxia-induced vascular changes. 6. Garlic pretreatment had no effect on the early transient contraction (+25 +/- 4%), but inhibited the transient relaxation (-5 +/- 3%; P<0.05) and the sustained contraction (+26 +/- 5%; 7. Garlic also significantly inhibited endothelin-l-induced contractions in a dose-dependent manner. 8. These findings show that garlic extract modulates the production and function of both endothelium-derived relaxing and constricting factors and this may contribute to its protective effect against hypoxic pulmonary vasoconstriction.     

钾通道开放剂尼可地尔和钾通道阻断剂氯化铯对缺氧引起离体大鼠肺动脉收缩反应的影响

目的　观察钾通道开放剂尼可地尔和钾通道阻断剂氯化铯对缺氧引起离体大鼠肺动脉环收缩反应的影响。方法　以０．９５Ｎ２＋０．０５ＣＯ２造成肺动脉环的缺氧性收缩反应;机械法去除肺动脉血管内皮细胞。结果　急性缺氧１ｈ后,含内皮与去内皮肺动脉环的ＫＣｌ诱导的最大收缩百分率（ＴＫｍａｘ％）分别为１６％±４％、１８％±５％（Ｐ＞０．０５）。有氧时,钾通道阻滞剂氯化铯（１０、２０ｍｍｏｌ·Ｌ－１）可略微提高肺动脉环的收缩张力,氯化铯４０ｍｍｏｌ·Ｌ－１引起的明显收缩,依赖细胞外Ｃａ２＋内流。缺氧可增强氯化铯的上述作用,氯化铯（１０、２０、４０ｍｍｏｌ·Ｌ－１）诱导肺动脉环产生的ＴＫｍａｘ％分别增加７５０％、３５４％、１７％。钾通道开放剂尼可地尔（３、１０、３０μｍｏｌ·Ｌ－１）可浓度依赖性地抑制缺氧及氯化铯诱导的肺动脉环收缩反应。含内皮与去内皮肺动脉环在上述反应中有相似性的表现。结论　急性缺氧造成非内皮依赖性肺动脉收缩反应,与平滑肌钾通道阻滞有关。氯化铯可增强此反应。尼可地尔对缺氧性肺动脉收缩反应的抑制作用,提示此类药物在临床治疗中的前景。     

埃他卡林对长期低氧大鼠肺动脉平滑肌KATP mRNA的影响

目的 :研究慢性低氧对大鼠肺动脉平滑肌ATP敏感钾通道 (KATP)mRNA表达的影响及新型KATP开放剂盐酸埃他卡林的作用。方法 :SD雄性大鼠 16只随机分成对照组、低氧组、低剂量治疗组 (盐酸埃他卡林 0 .75mg·kg-1·d-1,ig)、高剂量治疗组(盐酸埃他卡林 1.5mg·kg-1·d-1,ig)。将低氧组和治疗组大鼠放入常压低氧舱制备动物模型 ;采用RT PCR技术 ,分析各组肺动脉主干平滑肌KATP mR NA表达。结果 :低氧组SUR2mRNA水平显著低于正常组 ,高剂量治疗组SUR2显著高于低氧组 ,各组Kir 6 .1没有显著差异。结论 :慢性低氧抑制KATP 通道表达 ,而盐酸埃他卡林能提高表达 ,可从肺动脉高压发病机制上理解该药物治疗价值。     

Hypoxic pulmonary vasoconstriction and vascular contractility in monocrotaline-induced pulmonary arterial hypertensive rats

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling of pulmonary arteries (PAs) and increased vascular resistance in the lung. Monocrotaline (MCT), a toxic alkaloid, is widely used for developing rat models of PAH caused by injury to pulmonary endothelial cells; however, characteristics of vascular functions in MCT-induced PAH vary and are not fully understood. Here, we investigated hypoxic pulmonary vasoconstriction (HPV) responses and effects of various vasoconstrictors with isolated/perfused lungs of MCT-induced PAH (PAH-MCT) rats. Using hematoxylin and eosin staining, we confirmed vascular remodeling (i.e., medial thickening of PA) and right ventricle hypertrophy in PAH-MCT rats. The basal pulmonary arterial pressure (PAP) and PAP increase by a raised flow rate (40 mL/min) were higher in the PAH-MCT than in the control rats. In addition, both high K⁺ (40 mM KCl)- and angiotensin II-induced PAP increases were higher in the PAH-MCT than in the control rats. Surprisingly, application of a nitric oxide synthase inhibitor, L-N^G-Nitroarginine methyl ester (L-NAME), induced a marked PAP increase in the PAH-MCT rats, suggesting that endothelial functions were recovered in the three-week PAH-MCT rats. In addition, the medial thickening of the PA was similar to that in chronic hypoxia-induced PAH (PAH-CH) rats. However, the HPV response (i.e., PAP increased by acute hypoxia) was not affected in the MCT rats, whereas HPV disappeared in the PAH-CH rats. These results showed that vascular contractility and HPV remain robust in the MCT-induced PAH rat model with vascular remodeling.     

新型磷酸二酯酶5抑制剂CPD1对肺动脉高压大鼠血管收缩的影响

目的探讨新型磷酸二酯酶5抑制剂CPD1对肺动脉高压(pulmonary arterial hypertension,PAH)大鼠肺动脉和主动脉收缩效应的影响。方法一次性腹腔注射野百合碱(monocrotaline,MCT,50 mg·kg^-1),制备PAH大鼠模型,造模7 d后给予CPD1(10 mg·kg^-1·d^-1)灌胃治疗,持续14 d。通过血管环张力检测技术观察CPD1对MCT致PAH大鼠血管收缩效应的作用。结果成功制备PAH大鼠模型;CPD1治疗可显著降低PAH大鼠右心室收缩压和右心质量指数,改善肺小动脉内膜增生情况,抑制苯肾上腺素(phenylephrine,Phen)和内皮素-1(endothelin-1,ET-1)诱导的PAH大鼠肺动脉和主动脉的收缩效应,而对KCl诱导的血管收缩效应无影响。结论磷酸二酯酶5抑制剂CPD1干预能抑制PAH大鼠模型,其机制可能是CPD1抑制PAH大鼠非电压依赖性钙通道功能,引起血管收缩力降低、血管平滑肌增殖减弱和血管重塑减轻。     

异丙酚对大鼠肺动脉平滑肌细胞钾通道电流的影响

目的：评价异丙酚对正常血压及肺动脉高压大鼠肺动脉平滑肌K^＋通道的影响。方法：用SD大鼠建立肺动脉高压大鼠模型。急性分离正常血压和肺动脉高压大鼠肺内动脉平滑肌细胞，用膜片钳全细胞记录技术记录细胞K^＋通道电流。通过浴槽内给药。结果：在50、100μmol／L浓度下，异丙酚可明显引起正常血压和肺动脉高压大鼠肺动脉平滑肌细胞外向K^＋通道电流I-V曲线上移。与对照组比较，异丙酚作用后5min内细胞外向K^＋通道电流强度分别增强为初始电流强度的（121±11）％、（113±5）％（P〈0．01）和（126±5）％、（122±8）％（P〈0.01）。结论：异丙酚可增强正常血压及肺动脉高压大鼠动脉平滑肌细胞的外向K^＋通道电流，这可能是其降低肺血管张力、舒张肺血管的机制之一。     

Chronic salt loading and cardiovascular-associated changes in experimental diabetes in rats

1. High-sodium intake may increase blood pressure and diabetes is a salt-sensitive condition. In the present study, we evaluated cardiovascular changes and their neurohumoral mechanisms in streptozotocin (STZ)-diabetic rats that underwent chronic salt loading. 2. We studied male Wistar rats (150-280 g) 14 days after the injection of either STZ (50 mg/kg, i.v.; D; n = 18) or citrate buffer (C; n = 16). After the induction of diabetes, animals were maintained for 14 days with free access to standard rat chow and tap water (C and D groups) or 1% NaCl solution (C-S and D-S groups). We conducted two experiments. Experiment 1 consisted of basal arterial pressure (AP) measurement (30 min) followed by the evaluation of AP responsiveness to phenylephrine and sodium nitroprusside. One day later, with the rats anaesthetized, a blood sample was collected to test for glycaemia, plasma angiotensin-converting enzyme (ACE) activity and renin. Kidneys were removed for the determination of tissue ACE activity. Experiment 2 comprised 24 h urine collection followed by 3 days of cardiovascular records, which consisted of a 30 min basal AP measurement, followed by injection of blockers of the vasopressin system, the renin-angiotensin system (RAS) and the sympathetic system. Basal haemodynamic data, baroreflex evaluation and AP responses to blockade of the vasopressin system with vasopressin V(1) receptor antagonist (aAVP; 10 mg/kg, i.v.), the RAS by losartan (10 mg/kg, i.v.) and the sympathetic system by hexamethonium (20 mg/kg, i.v.) were determined. 3. Glycaemia was similar between C and C-S (P = 0.612) and between D and D-S (P = 0.552), but higher in diabetic compared with non-diabetic rats (P < 0.0001). The D-S rats had an increment of 24% in mean AP compared with D (120 +/- 4 vs 97 +/- 2 mmHg, respectively; P = 0.0001), which was not seen in C-S compared with C rats. A positive association was noted between urinary sodium and mean AP (r = 0.37; P = 0.04). Plasma renin was undetectable in D-S rats. The response to acute drug blockade of vasopressin and the RAS was similar among groups, but hexamethonium elicited a more pronounced decrease in AP in D-S compared with D rats (P = 0.001). 4. The main neurohumoral mechanisms of salt-induced cardiovascular changes in STZ-diabetes are increased sodium and vascular sensitivity to adrenergic stimuli, which act in combination to produce a final result of higher AP levels, a finding not observed in control rats. Baroreflex derangements induced by diabetes were not affected by salt overload.     

冠心病合并2型糖尿病患者冠状动脉造影特点分析

目的探讨冠心病合并2型糖尿病患者冠脉造影特点。方法观察冠心病合并2型糖尿病患者与非糖尿病的冠心病患者冠状动脉病变特点，结合临床进行分析对比。结果糖尿病组单支病变、二支病变、多支病变分别占23．10％、32．40％、44．44％，非糖尿病组单支病变、二支病变、多支病变分别占39、76％、31．32％、27、71％，糖尿病组弥漫性病变占75％，对照组60．24％。结论冠心病合并2型糖尿病患者冠状动脉病变更加广泛和严重。     

Pharmacokinetics of 5-fluorouracil in rats with diabetes mellitus induced by streptozotocin

The pharmacokinetic parameters of 5-fluorouracil were compared after intravenous administration at a dose of 30 mg/kg to control Sprague-Dawley rats and to rats with diabetes mellitus induced by streptozotocin (DMIS). In DMIS rats, the area under the plasma concentration-time curve from time zero to time infinity (AUC) was significantly smaller (603 versus 909 microg min/ml) due to the significantly faster total body clearance (Cl; 47.8 versus 33.0 ml/min/kg). The faster Cl was due to the significantly faster renal (8.54 versus 4.02 ml/min/kg) and nonrenal (38.5 versus 28.7 ml/min/kg) clearances. In DMIS rats, the total amount of unchanged 5-fluorouracil excreted in 24 h urine was significantly greater (34.1% versus 13.0% of intravenous dose) due to the urine flow rate-dependent renal clearance of 5-fluorouracil in rats (the greater the urine flow rate, the greater the urinary excretion of 5-fluorouracil). Greater urinary excretion and a significantly smaller AUC resulted in a significantly faster Cl(r) in DMIS rats. The faster Cl(nr) in DMIS rats could be due to an increase in the expression and mRNA level of CYP1A1/2 in the rats.     

Beneficial effects of aloe vera leaf gel extract on lipid profile status in rats with streptozotocin diabetes

The effect of diabetes mellitus on lipid metabolism is well established. The association of hyperglycaemia with an alteration of lipid parameters presents a major risk for cardiovascular complications in diabetes. Many secondary plant metabolites have been reported to possess lipid-lowering properties. The present study was designed to examine the potential anti-hyperlipidaemic efficacy of the ethanolic extract from Aloe vera leaf gel in streptozotocin (STZ)-induced diabetic rats. 2. Oral administration of Aloe vera gel extract at a dose of 300 mg/kg bodyweight per day to STZ-induced diabetic rats for a period of 21 days resulted in a significant reduction in fasting blood glucose, hepatic transaminases (aspartate aminotransferase and alanine aminotransferase), plasma and tissue (liver and kidney) cholesterol, triglycerides, free fatty acids and phospholipids and a significant improvement in plasma insulin. 3. In addition, the decreased plasma levels of high-density lipoprotein-cholesterol and increased plasma levels of low-density lipoprotein-and very low-density lipoprotein-cholesterol in diabetic rats were restored to near normal levels following treatment with the extract. 4. The fatty acid composition of the liver and kidney was analysed by gas chromatography. The altered fatty acid composition in the liver and kidney of diabetic rats was restored following treatment with the extract. 5. Thus, the results of the present study provide a scientific rationale for the use of Aloe vera as an antidiabetic agent.     

Pulmonary vascular reactivity of spontaneously hypertensive rats is exacerbated in response to the central administration of exogenous nitric oxide

1. Centrally, nitric oxide (NO) is a sympathoinhibitory substance. Spontaneously hypertensive rats (SHR) have an impaired central nitroxidergic system and, consequently, NO-mediated decrease in sympathetic activity is exacerbated in SHR compared with Wistar-Kyoto (WKY) rats. We have demonstrated previously that acute hypoxic pulmonary vasoconstriction (HPV) is enhanced by central NO administration. Therefore, in the present study, we hypothesized that accentuation of the HPV by NO would be exacerbated in SHR compared with WKY rats. 2. Mean pulmonary arterial pressure, systemic mean arterial blood pressure, cardiac output and heart rate were measured in pentobarbitone-anaesthetized, artificially ventilated, male SHR and WKY rats. The brief, transient response to a bolus intracerebroventricular (i.c.v.) dose of N(G)-nitro-L-arginine methyl ester (L-NAME; 150 microg in 10 microL) was recorded in all rats. Upon recovery, rats were exposed to acute hypoxia (10% O(2) for 4 min) before and after the i.c.v. administration of the NO donor 3-[4-morpholinyl]-sydnonimine-hydrochloride (SIN-1; 100 microg in 10 microL). 3. In WKY rats, central inhibition of NO synthesis by L-NAME caused a mild increase in tonic pulmonary vascular tone and induced a large systemic pressor response. These responses were not observed in SHR. In contrast, SIN-1 failed to alter tonic pulmonary vascular tone, although it enhanced the HPV in WKY rats and, significantly more so, in SHR. 4. These results confirm that accentuation of the HPV by NO is exacerbated in SHR compared with WKY rats. The mechanism(s) by which the HPV is accentuated by central NO remains to be fully elucidated, but is likely to be associated with the sympathoinhibitory effects of NO and, if so, supports the idea that the nitroxidergic system of the SHR is impaired. Further electrophysiological studies are essential to confirm these assumptions.     

高原低氧环境下盐酸二甲双胍在2型糖尿病及正常大鼠体内的药动学差异

目的 建立LC-MS/MS方法研究高原低氧环境下盐酸二甲双胍在2型糖尿病（T2DM）大鼠体内的药动学特征,并与正常大鼠体内的药动学特征进行差异分析。方法 高糖高脂饲料喂养合并ip链脲佐菌素（STZ）制备T2DM大鼠模型;采用Gemini C18（75 mm×3 mm,3μm）色谱柱分离,乙腈-水-甲酸（85：15：0.1）为流动相等度洗脱,质谱正离子多反应模式下定性定量分析;T2DM大鼠与正常大鼠分别单次ig给予二甲双胍后,采集血样,测定血浆药物浓度,采用DAS2.0药动学软件计算药动学参数。结果 二甲双胍质量浓度在25~16 000 ng·mL^-1内线性关系良好（r=0.999 2）,定量下限为25 ng·mL^-1;大鼠单次ig二甲双胍后,与正常大鼠组相比,T2DM大鼠二甲双胍药时曲线下面积（AUC）增加了25.15%,峰浓度（C_max）增加了28.28%,清除率（CL_z/F）减小了20.00%（P<0.05）。结论 高原低氧环境下,与正常大鼠相比,二甲双胍在T2DM模型大鼠体内的AUC、C_max、CL_z/F变化具有显著性差异。     

维格列汀伍用丹参舒心胶囊对早期2型糖尿病患者肺功能的影响

目的 观察维格列汀联合丹参舒心胶囊对早期二甲双胍单药治疗不佳的2型糖尿病(T2DM)患者肺功能的影响,并对其有效性及安全性进行评价.方法 选择早期(无微血管病变)经二甲双胍单药治疗且效果不佳的T2DM患者74例,随机分为观察组(n=38)和对照组(n=36),选择同期体检健康40例为健康组.对照组予二甲双胍(1000 mg、2次/d)、银杏叶提取物片(40 mg、3次/d)、甲钴胺(0.5 mg、2次/d)等口服治疗,观察组予二甲双胍500 mg、3次/d)、维格列汀(50 mg、2次/d)、银杏叶提取物片(40 mg、3次/d)+丹参舒心胶囊(0.4 g、2次/d)、甲钴胺(0.5 mg、2次/d)口服治疗.治疗前记录3组血糖及肺功能等基本资料.T2DM患者连续治疗24周后观察2组治疗后空腹血糖(FBG)、餐后2 h血糖(2 hPG)、体重指数(BMI)与肺功能[肺活量(VC%)、用力肺活量(FVC%)、1 s用力呼气流量(FEV1%)、最大呼气峰流速(PEF%)、最大自主通气量(MVV%)、肺总量(TCL%)、一秒率(FEV1/FVC%)、肺一氧化碳弥散量(DLCO%)、肺单位体积一氧化碳弥散量(DLCO/VA%)]的变化情况,记录治疗过程中的不良反应.结果 治疗前T2DM患者的FBG、2 hPG、BMI均高于健康组(P<0.05),肺功能各项指标均低于健康组(P<0.05).治疗后T2DM两组FBG、2 hPG均低于治疗前(P<0.05),但2组FBG、2 hPG及BMI治疗前后比较差异均无统计学意义(P>0.05).治疗后2组肺功能均优于治疗前(P<0.05),治疗后观察组肺功能优于对照组(P<0.05).结论 T2DM患者早期即出现肺功能下降,维格列汀联合丹参舒心胶囊在控制血糖的同时能较好改善患者的肺功能,且安全可靠,不增加体重.     

3、4-二羟基苯乙酮对大鼠肺内动脉平滑肌细胞钾电流的影响

目的　研究 3、4 二羟基苯乙酮 (3、4 Dihydroxyace tophenone,DHAP)对钾通道的作用。 方法　建立大鼠肺内动脉平滑肌全细胞膜片钳方法并观察 3、4 二羟基苯乙酮对大鼠肺内动脉平滑肌细胞钾离子通道的作用。结果　①将平滑肌细胞钳制在 - 4 0mV ,给予从 - 30mV复极化至 +6 0mV、阶跃电压为 10mV、脉冲时间是 30 0ms的去极化刺激10次时 ,可记录到时间及电压依赖性的延迟整流钾电流。②在指令电位 +5 0mV、+6 0mV时 ,细胞外给予 10 -6mol·L-1DHAP 5min后 ,可使该电流由用药前 (12 97± 2 4 5 )、(16 83± 3 2 8)pA/pF ,增加至 (18 2 9± 2 6 3)、(2 2 90±3 2 1)pA/pF ,增加百分比为 4 1%和 36 % (P <0 0 5 ,n =6 )。结论　DHAP可能通过开放钾通道而舒张肺内动脉平滑肌细胞 ,这可能是其降低肺动脉高压的重要机制之一。     

Ameliorative effects of glycyrrhizin on streptozotocin-induced diabetes in rats

Objectives Glycyrrhizin is the main water‐soluble constituent of the root of liquorice (Glycyrrhiza glabra). The study investigates the effect of glycyrrhizin on streptozotocin (STZ)‐induced diabetic changes and associated oxidative stress, including haemoglobin‐induced free iron‐mediated oxidative reactions. Methods Male Wistar rats were grouped as normal control, STZ‐induced diabetic control, normal treated with glycyrrhizin, diabetic treated with glycyrrhizin and diabetic treated with a standard anti‐hyperglycaemic drug, glibenclamide. Different parameters were studied in blood and tissue samples of the rats. Key findings Glycyrrhizin treatment improved significantly the diabetogenic effects of STZ, namely enhanced blood glucose level, glucose intolerant behaviour, decreased serum insulin level including pancreatic islet cell numbers, increased glycohaemoglobin level and enhanced levels of cholesterol and triglyceride. The treatment significantly reduced diabetes‐induced abnormalities of pancreas and kidney tissues. Oxidative stress parameters, namely, serum superoxide dismutase, catalase, malondialdehyde and fructosamine in diabetic rats were reverted to respective normal values after glycyrrhizin administration. Free iron in haemoglobin, iron‐mediated free radical reactions and carbonyl formation in haemoglobin were pronounced in diabetes, and were counteracted by glycyrrhizin. Effects of glycyrrhizin and glibenclamide treatments appeared comparable. Conclusion Glycyrrhizin is quite effective against hyperglycaemia, hyperlipidaemia and associated oxidative stress, and may be a potential therapeutic agent for diabetes treatment.     

替米沙坦对2型糖尿病大鼠心肌病变的干预研究

目的观察2型糖尿病大鼠心肌超微结构和心功能变化及替米沙坦对其的影响。方法雄性SD大鼠40只,单纯随机分为正常组（N组）、糖尿病模型组（M组）、替米沙坦干预组（T组）。M、T组大鼠高糖高脂饲料喂养4周后以25mg/kg链脲佐菌素（STZ）尾静脉1次性注射,建立2型糖尿病大鼠模型。N组常规饲料喂养4周后以等剂量的枸橼酸盐尾静脉注射。所有大鼠均以原饲料喂养。STZ注射后1周,T组给予替米沙坦8.34mg·kg^-1·d^-1,N、M组给予等量水灌胃,给药12周末结束实验,取血测空腹血糖（FBG）、空腹胰岛素（FINS）、总胆固醇（TC）、三酰甘油（TG）;制备电镜切片,监测心功能。结果M、T组血INS、TG均显著高于N组（P〈0.01）,T组INS、TG显著低于M组（P〈0.01）。结论替米沙坦能够改善糖尿病心肌病,机制可能与降低INS、TG有关。     

2型糖尿病下肢血管病变踝肱指数检测的临床意义

目的：研究踝肱指数（ ABI）在诊断2型糖尿病患者下肢动脉病变（ PAD）中临床意义与影响因素。方法采用多普勒血流探测仪检测2型糖尿病患者足背动脉、胫后动脉与肱动脉血压的比值,以ABI〈0.9为切割点分成PAD组和非PAD组,比较两组患者的临床资料并分析其危险因素。结果检出糖尿病下肢血管病变21例（19.8%）,其中无临床症状者10例。和非PAD组比较,PAD组患者年龄大,病程长,餐后2 h血糖（2 hPBG）、甘油三酯（TG）、低密度脂蛋白（LDL-C）、糖化血红蛋白（HbA1C）均明显升高,有显著性差异（P〈0.05）。结论踝肱指数可用于早期诊断糖尿病下肢血管病变,且无创、价廉、简单,患者易接受。高龄、病程长、高血糖、高TG、LDL-C是引起下肢血管病变的危险因素。     

5-羟基癸酸盐对低氧大鼠肺动脉平滑肌细胞转化生长因子β_1表达的抑制作用

目的探讨5-羟基癸酸盐(5-HD)降低低氧性肺动脉高压的作用机制。方法雄性SD大鼠每天(10.0±0.5)%O2处理8 h,连续7 d后,sc给予5-HD 5 mg·kg-1后再进行同样的低氧处理,每天1次,连续21 d。测定右心室肥厚指数(RVHI),右心导管法测肺动脉平均压(mPAP);分别用ELISA法检测肺组织、免疫组化法检测肺动脉和支气管上皮中转化生长因子β1(TGF-β1)的表达。结果与正常对照组比较,低氧模型组的mPAP,RVHI及TGF-β1在肺动脉及支气管上皮细胞中的表达均明显升高(P<0.05),TGF-β1在肺组织中表达无明显升高。与低氧模型组相比,5-HD 5 mg·kg-1组肺动脉平滑肌mPAP和TGF-β1表达明显下降(P<0.05);但RVHI及TGF-β1在肺组织及支气管上皮细胞中的表达无明显变化。结论 5-HD可能是通过TGF-β1信号通路发挥抗肺动脉平滑肌细胞的增殖作用而减轻肺动脉高压。     

Anti-diabetic effects of 1-methylnicotinamide (MNA) in streptozocin-induced diabetes in rats

1-Methylnicotinamide (MNA), a major endogenous metabolite of nicotinamide, possesses anti-thrombotic and anti-inflammatory activity, and reverses endothelial dysfunction. In the present work, we investigated whether such a vasoprotective profile of MNA activity affords anti-diabetic action in rats.Diabetes was induced by streptozotocin (STZ) in Sprague-Dawley rats. Eight weeks after STZ injection in untreated or MNAtreated rats (100 mg kg^–1 daily), development of diabetes (plasma concentrations of fasting and non-fasting glucose, HbA_1c, peptide C), development of oxidant stress (lipid peroxidation, carbonylation of plasma proteins), as well as NO-dependent endothelial function in aorta, coronary and mesenteric vessels were analyzed. Finally, the effect of chronic treatment with MNAon long-term survival of diabetic rats was determined.Chronic treatment withMNAprofoundly lowered fasting glucose concentrations in plasma, displayed mild effects on plasma HbA_1c and peptide C concentrations, while having no effects on non-fasting glucose. On the other hand, MNAtreatment considerably lowered lipid peroxidation, protein carbonylation, completely prevented impairment of endothelium-dependent vasodilatation in the aorta that was mediated entirely by NO, but failed to affect endothelial function in resistant vessels, which was mediated only partially by NO. Most importantly, chronic treatment with MNAprolonged the long-term survival of diabetic rats. In conclusion, MNA displayed a significant anti-diabetic effect that may be linked to its vasoprotective activity.