同型半胱氨酸对KKAy鼠心肌病变的影响

目的　观察高同型半胱氨酸血症对糖尿病小鼠心脏的影响 ,以及补充叶酸对心肌病变的作用。方法　 2 4只KKAy小鼠随机分三组 ,分别喂养高热量饮食 (KA组 )、高蛋氨酸饮食 (KB组 )以及高蛋氨酸加叶酸和维生素B12饮食 (KC组 )。测定各组血浆同型半胱氨酸、叶酸和维生素B12水平 ,并观察心肌病理改变。结果　饲养 16周后发现 ,高蛋氨酸饮食组血浆同型半胱氨酸明显增高 (2 9.33± 16 .85对 5 .33± 2 .0 3,P <0 .0 0 1) ,且心肌间质纤维化、钙化、小动脉管壁增厚和透明变性等病变加重 ,经叶酸和维生素B12治疗后血浆同型半胱氨酸降至正常 (4 .0 4± 1.81) ,且心肌病变减轻。结论　同型半胱氨酸可以加重糖尿病鼠的心肌病变 ,叶酸和维生素B12可以有效减缓这一病变进程。     

同型半胱氨酸对Kkay小鼠糖尿病肾病作用机制的探讨

目的 探讨基质金属蛋白酶-9(MMP-9)在同型半胱氨酸(Hcy)加重糖尿病肾病(DN)过程中的可能作用。方法 22～24周龄Kkay糖尿病鼠16只随机分两组:糖尿病组(KA)和高蛋氨酸组(KB),每组8只;C57BL/6小鼠9只为对照组(C57),以相应饲料喂养4个月后取材。测定血糖和血Hcy水平,以PAS染色观察各组肾组织肾小球病理改变,比较肾小球硬化指数(GI)。对肾脏MMP-9表达进行免疫组化染色和半定量图像分析,并以逆转录PCR检测。肾脏MMP-9 mRNA的表达水平。结果 与C57对照组相比,Kkay两组均有不同程度糖尿病肾病病变,其中KB组病变更重,其GI值(283.33)高于KA组(240.00),P<0.05。免疫组化显示KB组肾小球MMP-9阳性着色面积(15.90％)高于KA组(11.14％),P<0.05,MMP-9 mRNA表达水平KB组高于KA组。结论 高Hcy血症具有加重Kkay小鼠糖尿病肾病程度的作用,此作用可能与上调MMP-9的表达水平有关。     

同型半胱氨酸与冠状动脉病变关系的分析

目的 了解血清同型半胱氨酸、叶酸及维生素Ｂ１２水平与冠心病的关系。方法 用断面调查的方法率冠状动脉造影确诊的冠心病患者２０９例,非冠心病患者１１６例,用高效液相色谱法测定血清同型半胱氨酸水平,用放免法测定血清叶酸及ＶｉｔＢ２水平。结果 冠状动脉粥样硬化病变的发生与男性、年龄大、吸烟、糖尿病及血 同型半胱氨酸升高明显相关,与叶酸及ＶｉｔＢ１２水平的降低明显相关,并发现叶酸、ＶｉｔＢ１２与同型半胱氨酸     

雌激素对同型半胱氨酸水平和心肌雌激素受体的影响

目的雌激素对大鼠血浆高同型半胱氨酸(Hcy)水平和心肌雌激素受体(ER)mRNA表达水平的影响.方法蛋氨酸饮食喂养去势雌性Wistar大鼠构建高Hcy血症动物模型,造模同时给予皮下注射雌激素干预的为预防组,造模后再给予皮下注射雌激素干预的为治疗组.高压液相色谱法测定血浆Hcy水平,逆转录聚合酶链式反应法(RT-PCR)半定量检测心肌ER mRNA表达水平.结果高蛋氨酸饮食喂养90 d后,造模组大鼠Hcy水平明显高于对照组(P＜0.05),2组ERα和ERβ基因转录水平差异无统计学意义.预防组血浆Hcy水平低于造模组,心肌ERα mRNA水平高于造模组;预防组和治疗组心肌ERβ mRNA水平和造模组比较差异无统计学意义(P＞0.05).结论预防应用雌激素可以降低血浆Hcy水平,升高心肌ERα mRNA水平,但对其心肌ERβmRNA水平未见影响.     

叶酸对高血压患者血同型半胱氨酸疗效观察

目的探讨叶酸对高血压患者高同型半胱氨酸治疗效果。方法采用荧光标记免疫检测法进行检测。结果治疗组血同型半胱氨酸水平显著低于对照组。结论叶酸可降低高血压患者血同型半胱氨酸水平，减少其危害作用。     

冠心病人同型半胱氨酸水平的主要影响因素

目的　分析影响冠心病人血浆同型半胱氨酸水平的主要非遗传因素。方法　 16 4例住院冠心病患者 ,测定血浆同型半胱氨酸水平并分析其与血浆及全血叶酸、血浆维生素B12 、血清雌二醇浓度以及冠心病传统危险因素之间的关系。结果　血浆同型半胱氨酸水平与叶酸、维生素B12 水平呈负相关 ,男性血浆同型半胱氨酸浓度高于女性 [(2 0 74± 13 42 )× 10 -6mol/L比 (15 5 6± 8 16 )× 10 -6mol/L ,P <0 0 5 ],吸烟者高于不吸烟者 [(2 2 2 9± 15 18)× 10 -6mol/L比 (17 2 1± 9 5 4)× 10 -6mol/L ,P <0 0 5 ]。结论　叶酸、维生素B12 、性别和吸烟是影响冠心病患者血浆同型半胱氨酸水平的主要非遗传因素     

同型半胱氨酸、动脉粥样硬化与卒中

作为新的卒中危险因素，血浆同型半胱氨酸(Hcy)水平升高已受到高度重视。文章对血浆Hcy水平升高与动脉粥样硬化的因果关系，叶酸在血浆高Hcy血症中的作用，以及Hcy在卒中后的变化规律作了综述。     

同型半胱氨酸对老年2型糖尿病患者大血管病变的影响

目的 探讨血清总同型半胱氨酸(tHcy)水平与2型糖尿病(T2DM)患者大血管病变间的关系,并分析影响T2DM患者tHcy代谢的因素. 方法 167例老年T2DM 患者分为2组:无大血管并发症组(75例)和T2DM合并大血管病变组(92例);42例正常体检老人作为正常对照组.酶联免疫吸附法测定血清tHcy浓度;自动生化分析仪测定空腹血糖(FBS)、尿素氮(BUN)、肌酐(CREA)、总胆固醇(TC)和三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、糖化血红蛋白(HbA1c);电化学发光仪测定血清胰岛素(INS).对各指标的组间差异进行统计学分析. 结果 tHcy在T2DM合并大血管病患者组血浆浓度较T2DM无大血管并发症组和对照组高,差异具有统计学意义(P＜ 0.05),血清Hcy水平仅与空腹INS水平呈正相关(r= 0.56,P＜0.01). 结论 tHcy参与了T2DM大血管病变的发病过程,tHcy水平可能与胰岛素抵抗有关.     

脓毒症患者同型半胱氨酸与心肌损伤的相关性分析

目的 研究脓毒症患者脓毒症患者同型半胱氨酸(Hcy)与心肌损伤相关性.方法 选择我院收治30例脓毒症患者为观察组,另择取同期健康体检者30例为对照组,均行常规检查.结果 与对照组比较,观察组PCT、cTnI、NT-proBNP、Hcy指标较高,LVEF指标较低(P<0.05).结论 Hcy水平能准确评估脓毒症患者的心肌损伤程度,为后期治疗提供参考.     

高同型半胱氨酸血症对糖尿病肾病小鼠细胞间黏附分子-1表达的影响

目的　探讨高同型半胱氨酸 (Hcy)血症对糖尿病肾病 (DN)时细胞间黏附分子 1(ICAM 1)表达的影响。　方法　 2 2～ 2 4周龄Kkay糖尿病鼠 16只随机分两组 :糖尿病 (KA)组和高蛋氨酸 (KB)组 ,每组 8只 ;另以 9只C5 7BL/ 6小鼠为对照 (C5 7) ,以相应饲料喂养 4个月后取材。测定血糖和血Hcy水平 ,以PAS染色观察各组DN病变。对肾脏ICAM 1蛋白表达进行免疫组化染色和半定量图像分析 ;并以RT PCR检测肾脏ICAM 1mRNA的表达水平。　结果　与C5 7对照组相比 ,Kkay两组均有不同程度DN病变 ,其中KB高蛋氨酸组病变最重 ,其肾小球硬化指数 (GI)高于KA组 (P <0 0 5 )。免疫组化显示Kkay小鼠肾脏ICAM 1的表达高低与病理变化一致 ,即KB组ICAM 1阳性着色面积 (19 6 5 % )高于KA组 (15 2 2 % ) (P <0 0 1) ;ICAM 1mRNA表达水平也强于KA组。　结论　Hcy具有加重Kkay小鼠DN程度的作用 ,此作用可能与上调ICAM 1的表达水平有关     

依帕司他对糖尿病周围神经病变患者同型半胱氨酸和多伦多临床评分的影响

目的探讨依帕司他对糖尿病周围神经病变(DPN)患者血清同型半胱氨酸(Hcy)及多伦多临床评分系统(TCSS)评分的影响。方法入选2016年4月至2017年4月怀化市第一人民医院内分泌代谢科2型糖尿病患者97例,随机数表法分为依帕司他组(n=33)、依帕司他联合甲钴胺组(n=30)和甲钴胺组(n=34)。甲钴胺片0.5 mg/次,依帕司他片50 mg/次,2种药物均口服,3次/d。治疗周期3个月。比较3组患者治疗前后空腹血糖(FBG)、餐后2小时血糖(2hPBG)、糖化血红蛋白(HbA1c)、Hcy和TCSS水平。应用SPSS 21.0统计软件对数据进行分析。依据数据类型组间比较采用方差分析或χ~2检验。LSD法进行两两比较。结果 3组患者治疗后FBG、2hPBG、HbA1c水平相比治疗前均下降,但差异无统计学意义(P0.05)。3组患者治疗前Hcy和TCSS水平差异无统计学意义(P0.05)。3组患者治疗后相比治疗前Hcy水平[(11.39±1.39)vs(13.40±2.26)μmol/L;(11.27±2.46)vs(13.51±2.32)μmol/L;(10.13±1.84)vs(14.91±6.78)μmol/L]下降,依帕司他组和依帕司他联合甲钴胺组治疗后相比治疗前TCSS评分[(7.64±1.87)vs(8.30±2.59);(5.83±1.88)vs(9.13±2.91)]下降,差异均有统计学意义(P0.05)。依帕司他联合甲钴胺组治疗后相比依帕司他组和甲钴胺组Hcy[(10.13±1.84)vs(11.39±1.39),(11.27±2.46)μmol/L]和TCSS评分[(5.83±1.88)vs(7.64±1.87),(8.59±2.22)]水平低,差异均有统计学意义(P0.05)。结论依帕司他联合甲钴胺缓解糖尿病患者DPN效果明显,可推广应用。     

促血小板生成素对小鼠药物性心肌损伤的保护作用

目的研究促血小板生成素（thrombopoietin,TPO）的心肌保护作用。方法小鼠分为对照组、多柔比星组、TPO组。多柔比星组及TPO组小鼠第1天予多柔比星20 mg/kg经腹腔注射;TPO组小鼠予TPO 15μg/kg,共3次经腹腔注射。第1天（多柔比星注射前）和第5天予小鼠做超声心动图检查;第5天取小鼠心肌组织行苏木素伊红染色,显微镜下评价心肌组织损伤程度。比较第1～8天内多柔比星组和TPO组存活率。结果与第0天相比,第5天多柔比星组的心率、每分钟心输出量、左心室短轴缩短率明显下降,差异有统计学意义（P〈0.05）;镜下见小鼠心肌组织明显损伤,说明药物性心肌损伤的模型能成功建立。相对多柔比星组,TPO组心率、每分钟心输出量、左心室短轴缩短率明显改善,差异有统计学意义（P〈0.05）。TPO组镜下评分示心肌损伤显著降低,8 d内的生存率明显高于多柔比星组,差异有统计学意义（P〈0.05）。结论 TPO对损伤心肌有保护作用。     

Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid

Abstract. Objectives . Moderate hyperhomocysteinaemia is an independent risk factor for cardiovascular disease which may be causal. We investigated whether the concentration of plasma homocysteine changes between the acute phase of myocardial infarction and follow-up, and whether treatment with oral folic acid was effective in lowering homocysteine levels in patients with myocardial infarction. Design and subjects . Plasma total homocysteine levels 24–36 h (baseline) after onset of acute myocardial infarction were compared with the levels obtained at 6 weeks' follow-up and with the levels in the controls. In the same patients, we studied the effect on plasma homocysteine of 6 weeks' treatment with daily oral folic acid doses of 2.5 or 10 mg compared to no treatment. Results . At baseline, 12 of 68 patients (18%) had moderate hyperhomocysteinaemia (>17.3 μmol L^?1; P < 0.05). Between baseline and follow-up, plasma homocysteine levels increased from 13.1 ± 4.6 to 14.8 ± 4.8 μmol L^?1 (mean ± SD; P < 0.001). Treatment with nitroglycerin, streptokinase, beta blockers, or acetylsalicylic acid seemed not to have caused this change. Folic acid lowered plasma homocysteine in all but two of 33 treated patients with a mean decrease of 4.4 μmol L^?1 (–27%; P < 0.001). There was no difference between the effect of 2.5 and 10 mg of folic acid. In the untreated group (n = 20), plasma homocysteine increased with a mean increase of 0.6 μmol L^?1 (+ 4%; P < 0.05). Conclusions . Plasma homocysteine seems to increase in the post myocardial infarction period, the cause of which warrants further study. Folic acid appears to be an effective treatment for the reduction of both normal and increased plasma homocysteine concentrations in patients with myocardial infarction. This suggests that folic acid should be used for intervention when studying the effect of homocysteine-lowering therapy on the risk on myocardial infarction.     

大黄素对糖尿病KKAy小鼠PI3-K信号转导通路的影响

目的 观察大黄素对2型糖尿病模型KKAy小鼠血糖、胰岛素水平及磷脂酰肌醇3-激酶(PI3-K)信号转导通路的影响.方法 随机血糖均≥13.9 mmol/L的SPF级KKAy小鼠16只,随机分为模型组和治疗组各8只,另选8只C57BL/6J小鼠为正常组.正常组和模型组灌服20 mL/(d·kg)无菌水,治疗组予50 mg/kg大黄素灌胃.8周后测定各组小鼠空腹血糖(FPG)、空腹胰岛素(HNS)并计算胰岛素敏感指数(ISI);用Western blot法测定三组小鼠骨骼肌、脂肪组织中胰岛素受体底物-1( IRS-1)、PI3-K水平及Akt丝氨酸(Ser)473磷酸化水平.结果 模型组小鼠较正常组FPG、FINS明显升高,ISI明显降低,而治疗组小鼠的FPG、FINS较模型组明显降低,ISI明显升高(P均＜0.05).模型组IRS-1、PL3 -K表达水平及胰岛素刺激后Akt Ser473磷酸化升高倍数低于正常组,治疗组IRS-1、PI3-K表达水平及Akt Ser473磷酸化升高倍数高于模型组(P均＜0.05).结论 大黄素灌胃可降低2型糖尿病模型KKAy小鼠血糖、胰岛素水平,并增强胰岛素敏感度,提高小鼠骨骼肌及脂肪组织中的IRS-1、PI3 -K水平及Akt Ser473磷酸化水平.     

老年新诊2型糖尿病患者血浆同型半胱氨酸与颈动脉硬化的关系

目的探讨老年新诊2型糖尿病患者血浆同型半胱氨酸(Hcy)与颈动脉硬化的关系。方法测定92例老年新诊2型糖尿病患者和48例健康对照者(对照组)的血浆Hcy、血清白细胞介素-8(IL-8)、叶酸、维生素B12、颈动脉内膜中层厚度(IMT)。将糖尿病患者分为IMT正常组(24例)I、MT增厚组(24例)、斑块组(44例);再将斑块组分为稳定斑块亚组(32例)、不稳定斑块亚组(12例),并进行分析。结果新诊2型糖尿病患者血浆Hcy水平明显高于对照组(P<0.05),且在IMT正常组、IMT增厚组、斑块组逐步升高(P<0.05),并且不稳定斑块亚组高于稳定斑块亚组(P<0.05)。血浆Hcy水平与IL-8呈正相关,与叶酸、维生素B12呈负相关。结论Hcy是老年新诊2型糖尿病患者颈动脉硬化的重要危险因素之一,并可能通过IL-8参与动脉硬化的发展;血浆Hcy水平与颈动脉硬化的程度及斑块的稳定性有关。     

同型半胱氨酸水平与冠心病的关系

目的观察同型半胱氨酸(Hey)水平与冠心病(CHD)的关系,并探讨蛋氨酸合成酶还原酶(MTRR)A66G基因多态性、叶酸、维生素B12(VitB12)与Hcy水平及CHD的关系。方法 选择190例经冠状动脉造影证实的CHD患者(CHD组)和100例冠状动脉造影正常者为对照组。应用荧光偏振免疫分析法测定Hey水平,离子捕获分析法测定叶酸水平,微粒酶免疫分析法测定VitB12水平。聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析MTRRA66G基因多态性。结果 CHD组血Hcy水平显著高于对照组(15.8±8.8)μmol/L与(12.9±6.3)μmol/L,P=0.002。叶酸、VitB12水平与血Hcy水平呈负相关。叶酸、VitB12与CFD无关。MTRR A66G基因多态性GG纯合子、AG杂合子和AA野生型3种基因型组间血Hcy水平差异无显著性意义。(P=0.908)。MTRR A66G各基因型在CHD组和对照组的分布差异无显著性意义(P=0.198)。结论CHD患者血Hcy水平升高,叶酸、VitB12水平与血Hcy水平呈负相关。MTRR A66G基因多态性与血Hcy水平及与CHD均无关。     

糖尿病大鼠心肌细胞超微结构变化及西洛他唑的干预作用

目的观察糖尿病（DM）大鼠心肌细胞超微结构变化及西洛他唑对其干预作用。方法将DM大鼠随机分为西洛他唑治疗组和DM组,用药8周后检测两组血糖、体质量、糖化血红蛋白、心脏重量指数,观察其心肌细胞超微结构变化。结果两组比较,除治疗组心脏重量指数低于DM组外（P〈0．05）,其余无统计学差异。治疗组心肌细胞变化较DM组明显减轻（P〈0．05）。结论西洛他唑对DM大鼠的心肌损伤有保护作用。     

氯沙坦对自发性2型糖尿病KKAy小鼠肾脏损害的保护作用

目的探讨氯沙坦在治疗KKAy小鼠糖尿病早期肾损害中的应用价值。方法将20只雄性8周龄KKAy小鼠随机分为治疗组（n=10）和非治疗组（n=10）,治疗组从8周龄始予以氯沙坦10 mg/（kg.d）饮水喂入,C57BL/6小鼠为正常对照组（n=10）。于20周龄测定各组小鼠血糖、尿微量白蛋白、尿肌酐,并留取肾脏标本,于光镜及电镜下观察其肾脏病理改变。结果氯沙坦治疗对KKAy小鼠体质量及血糖无影响;与非治疗组比较,氯沙坦治疗减少了KKAy小鼠的尿白蛋白/肌酐比率（P〈0.05）,改善了KKAy小鼠的病理损害。结论氯沙坦治疗能减少KKAy小鼠尿白蛋白排泄率,改善肾脏病理损害。     

Dapagliflozin's effect on serum homocysteine in patients with hypertension complicated with insulin resistance

Most patients with hypertension are complicated with insulin resistance (IR), which is one of the risk factors of hypertension and can increase the level of serum homocysteine (Hcy) by affecting Hcy's metabolic enzyme and insulin level. Investigations in recent years have shown that Hcy is an independent risk factor for cardiovascular diseases. At present, folic acid is the prominent medicine used to reduce Hcy, but its effection for Hcy has an obvious individual difference, which is closely related to individual genes. Moreover, folic acid is chiefly used in patients with Hcy ≥15 μmol/L, but Hcy ≥10 μmol/L has had an adverse effect on the cardiovascular system. Randomized clinical trials have shown that dapagliflozin can improve IR. Therefore, whether it can reduce Hcy has become a new direction. This study was a retrospective case–control study. Patients with high serum Hcy and hypertension complicated with IR were divided into two groups: the dapagliflozin group (n = 166) and the control group (n = 198). Before and after 12 weeks of treatment, the changes in serum Hcy and IR index were measured and compared. We found that dapagliflozin could reduce the serum Hcy level of patients with hypertension and IR to a certain extent. Dapagliflozin could be a viable option for hypertension complicated with IR and hyperhomocysteinemia. However, these findings need to be further confirmed in future randomized clinical trials with a large number of samples.     

Effect of folic acid and betaine on fasting and postmethionine-loading plasma homocysteine and methionine levels in chronic haemodialysis patients

OBJECTIVES: To study fasting and postmethionine-loading (increment and decrement) plasma homocysteine levels in end-stage renal disease (ESRD) patients in relation to B-vitamin status and after folic acid treatment without or with betaine. DESIGN: Plasma total homocysteine (tHcy) and methionine levels were measured in chronic haemodialysis patients after an overnight fast, and 6 and 24 h after an oral methionine load (0.1 g kg-1). The patients were subsequently randomized to treatment with folic acid 5 mg daily with or without betaine 4 g daily, and the loading test was repeated after 12 weeks. The patients were then re-randomized to treatment with 1 or 5 mg folic acid daily for 40 weeks, after which a third loading test was performed. SETTING: Haemodialysis unit of university hospital and centre for haemodialysis. SUBJECTS: Twenty-nine consecutive maintenance (> 3 months) haemodialysis patients, not on folic acid supplementation, 26 of whom completed the study. RESULTS: At baseline, the mean fasting, the 6 h postload and the 6 h postload increment plasma tHcy levels were increased as compared with those in healthy controls (46.8 +/- 6.9 (SEM), 92.8 +/- 9.1 and 46.0 +/- 4.2 mumol L-1, respectively) and correlated with serum folate (r = -0.42, P = 0.02; r = -0.61, P = 0.001 and r = -0.54, P = 0.003, respectively), but not with vitamin B6 or vitamin B12. At week 12, these variables had all decreased significantly. Betaine did not have additional homocysteine-lowering effects. At week 52, fasting and postload tHcy levels did not differ significantly between patients on 1 or 5 mg folic acid daily. Plasma tHcy half-life and plasma methionine levels after methionine loading were not altered by folic acid treatment. CONCLUSIONS: In chronic haemodialysis patients, fasting as well as postmethionine-loading plasma tHcy levels depend on folate status and decrease after folic acid therapy. Increased postload homocysteine levels in these patients therefore do not necessarily indicate an impaired transsulphuration capacity only; alternatively, folate may indirectly influence transsulphuration. The elucidation of the complex pathogenesis of hyperhomocysteinaemia in chronic renal failure requires further investigation.