瞬时外向钾电流在糖尿病心肌病电重构中的作用

目的：探讨糖尿病心肌病（DCM）大鼠心室肌细胞瞬时外向钾电流（Ito）的变化,了解其在电重构中的作用。方法选用20只健康成年SD大鼠,随机分为对照组（n=10）和DCM组（n=10）,并通过病理组织学证实为DCM心肌病理学改变。分别对两组大鼠采用改进的耐钙成年大鼠急性酶分离方法分离心肌细胞,运用膜片钳技术以全细胞模式分别记录两组大鼠心室肌单细胞的Ito和膜电容,并分析比较两组大鼠心室肌Ito的变化。结果与对照组比较,DCM组大鼠左心室心肌细胞的Ito电流密度显著低于对照组[＋70 mV时,（16.80±9.10） pA/pF v s（36.25±5.20）pA/pF]（P〈0.05）,DCM组的Ito的I-V曲线明显较对照组下移。结论 DCM的Ito数量明显减少,在DCM心肌电重构中起着重要作用。 Ito的减少及Ito通道的分布密度不同,可导致动作电位时程与有效不应期发生变化,可能与临床严重心律失常的发生有关。     

内源性硫化氢对高肺血流大鼠肺血管重构及血管活性物质的影响

目的探讨内源性硫化氢(hydrogen sulfide,H2S)对大鼠高肺血流性肺血管结构重建及血管活性肽的影响。方法♂SD大鼠32只随机分为分流组、分流+PPG(炔丙基甘氨酸,内源性H2S合成酶的抑制剂)组、对照组和对照+PPG组,每组8只。经腹主动脉-下腔静脉穿刺建立动物模型。分流4wk后,应用敏感硫电极法测定大鼠肺组织硫化氢(H2S)含量;应用放免试剂盒测定血浆中内皮素(ET-1)、心钠素(ANP)、降钙素基因相关肽(CGRP)及肾上腺髓质素(ADM)的含量;观察肺小血管的显微结构变化;结果分流4wk后,大鼠肺组织H2S水平升高,肺血管结构重建,血浆ET-1、ANP、CGRP及ADM升高。PPG干预后,肺组织H2S水平降低,肺血管结构重建加重,血浆ET-1、ANP、CGRP升高,而ADM降低。结论内源性H2S对高肺血流性肺血管结构重建具有重要的保护作用,并对多种血管活性肽具有调节作用。     

梓醇促进局灶脑缺血大鼠皮质脊髓束芽生和重塑

目的观察梓醇对局灶脑缺血大鼠病灶对侧皮质脊髓束(corticospinal tract,CST)轴突芽生和重塑的影响。方法30只SD大鼠随机分为假手术组、模型组、生理盐水组、梓醇治疗组和胞磷胆碱对照组。开颅电凝右侧大脑中动脉,制备局灶永久性脑缺血模型,造模后24 h首次经腹腔注射梓醇(5 mg·kg-1)或胞磷胆碱(0.5 g·kg-1),每日1次,连续7d。采用黏贴物移除实验和足失误实验测试受累前肢(左前肢)功能状况;核磁共振(MRI)测量脑梗死体积;生物素化葡聚糖胺(biotinylated dextran amine,BDA)顺行示踪健侧CST,检测脊髓颈膨大区健侧CST越边至失神经支配侧的纤维数量,了解脊髓颈膨大区CST轴突重塑;免疫荧光双标脊髓颈膨大区BDA标记纤维与生长相关蛋白(growth-associatedprotein,GAP-43),检测BDA/GAP-43共定位信号,了解脊髓颈膨大区CST轴突芽生能力。结果造模后7、14、21和28d,梓醇组和胞磷胆碱组左前肢黏贴片移除时间均比模型组和生理盐水组明显缩短(P<0.05),左前肢失误率也较模型组和生理盐水组明显降低(P<0.05);其中,造模后28 d时,梓醇组左前肢感觉运动功能状况明显优于胞磷胆碱组(P<0.05)。造模后1和28 d,各组脑梗死体积差异无显著性(P>0.05)。造模后28 d,梓醇组脊髓颈膨大区健侧CST越边纤维占(8.5%±2.1%),较模型组(4.7%±1.3%)和胞磷胆碱组(5.5%±1.8%)明显增加(P<0.05);梓醇组脊髓颈膨大区BDA/GAP-43共定位信号明显强于模型组和胞磷胆碱组(P<0.05)。结论梓醇可增强缺血性脑卒中大鼠皮质脊髓束轴突芽生和重塑能力,有助于受累肢体感觉运动功能恢复。     

不同剂量氟伐他汀对慢性心力衰竭大鼠心肌组织血管紧张素Ⅱ和脑利钠肽水平影响的实验研究

目的 探讨不同剂量氟伐他汀对阿霉素诱导的慢性心力衰竭大鼠心肌组织血管紧张素Ⅱ(AngⅡ)和脑利钠肽(BNP)水平的影响. 方法将60只SD大鼠随机分为正常对照组、心力衰竭对照组、小剂量氟伐他汀组和大剂量氟伐他汀组,除正常对照组予0.9%氯化钠注射液腹腔注射外,余3组均采用阿霉素腹腔注射的方法建立慢性心力衰竭大鼠模型.模...     

缺氧诱导因子与支气管哮喘

缺氧诱导因子(hypoxia-inducible factor,HIF)是细胞及组织缺氧情况下产生的一种氧依赖的转录激活因子,广泛存在于哺乳动物体内.能诱导多种缺氧反应性表达,使细胞及组织产生一系列反应以适应缺氧环境[1].研究发现在常氧状态下HIF-1a在支气管肺组织中有少量表达,而在支气管哮喘(简称哮喘)大鼠支气管肺组织中HIF-1a表达的量则明显增加,认为HIF-1a参与哮喘的发病机制[2].目前,国内外对该方面的研究很少.现就HIF与哮喘的关系作一综述.     

支气管哮喘气道重塑研究进展

支气管哮喘(简称哮喘)是以气道慢性炎症和气道重塑为基本特征的慢性疾病.气道重塑的确切机制尚不清楚,目前认为主要与气道慢性炎症有关,上皮损伤及上皮间充质营养单位再活化在气道重塑发病中也起重要作用.治疗哮喘的传统药物对气道重塑作用有限,近年应用抗肿瘤坏死因子α、CpG-ODN、抗IgE抗体和抗Th2细胞因子等免疫调节剂治疗气道重塑,支气管热整形术是有创性治疗技术.     

前列腺素E2与支气管哮喘关系研究进展

前列腺素E2在支气管哮喘(简称哮喘)发病机制中具有调节气道免疫功能,直接影响气道平滑肌细胞的收缩与舒张功能,并通过影响气道平滑肌细胞的迁移性生长,导致哮喘的气道重塑.本文主要对上述方面的研究进展作一综述.     

强心冲剂对心衰家兔细胞凋亡及心室重塑的影响

目的:建立家兔充血性心衰模型,以探讨强心冲剂在调节细胞凋亡及抑制心室重塑方面的作用。方法:将60只家兔随机分为6组,假手术组、模型组、地高辛组、低、中、高三个剂量强心冲剂组,每组lO只,采用腹主动脉缩窄术建立家兔CHF模型,予强心冲剂和地高辛灌胃9天,免疫组化方法测定心肌细胞凋亡相关基因表达的变化。结果:心衰家兔Bax表达明显增加,与此同时Bcl-2及肌动蛋白(α-actin)表达明显降低;而与模型组相比,强心冲剂组和地高辛组则明显下调Bax蛋白表达,上调Bcl-2及肌动蛋白表达,并且强心冲剂作用优于地高辛。结论:强心冲剂能通过调节某些心肌凋亡基因表达,从而抑制心肌细胞凋亡的发生,这可能是其干预心室重构,防治心力衰竭的机制之一。     

Effects of Xin-Ji-Er-Kang formula on 2K1C-induced hypertension and cardiovascular remodeling in rats

Ethnopharmacological relevance

Xin-Ji-Er-Kang (XJEK), a Chinese herbal formula, is effective against hypertension induced coronary heart disease, viral myocarditis and toxic myocarditis. In this study, the effect of XJEK on cardiovascular system was investigated. To test the hypothesis that Xin-Ji-Er-Kang (XJEK) has an anti-hypertensive effect mediated through attenuation of cardiac remodeling, and amelioration of vascular endothelial dysfunction and oxidative stress.

Materials and methods

Hypertension was induced in Wistar rats by 2 kidney 1 clip (2K1C) treatment. The hypertensive rats were then randomly assigned into four groups and treated as follows: group 1 (Sham-operated [Sh-Op] group received only drinking water), group 2 (induced hypertensive model+no treatment), and group 3 (induced hypertensive+a single daily oral dose of 24 g kg⁻¹ XJEK treatment) and group 4 (induced hypertensive+a single oral dose of 15 mg kg⁻¹ Fosinopril treatment). The rats in all the defined groups were respectively treated for a period of 4 weeks. Cardiovascular parameter such as systolic blood pressure (SBP) was measured weekly by using tail-cuff apparatus; left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and the rate of the rise in left ventricular pressure (±dp/dt max) were measured by using a PowerLab 8/30 apparatus (AD Instruments, Australia) at the end of the 8th week; heart weight/body weight (HW/BW) was determined as an index of myocardial hypertrophy (MH). Hematoxylin and eosin (H&E) and Van Gieson (VG) stain were used to assess the cardio-histological changes. Colorimetric analysis was used to assay serum superoxide dismutase (SOD) activity, malondialdehyde (MDA), nitric oxide (NO), and hydroxyproline (Hyp) contents in cardiac tissue. Angiotensin II (Ang II) content in serum was assessed by radioimmunoassay; tetrahydrobiopterin (BH₄) content in cardiac tissue, BNP and endothelial NOS (eNOS) in serum were determined by using ELISA, and the protein expressions of c-Jun NH2-terminal kinase (JNK), P-JNK, p38, P-p38, and NADPH oxidases-2 (Nox-2) were measured by western blot.

Results

XJEK therapy could impair the heart systolic and diastolic function, potently improve the heart weight index, inhibit the elevation of HW/BW ratio, and markedly ameliorate hemodynamic indices and vascular remodeling index. It has blunted the decrease of SOD, NO and the increase in MDA and Ang II serum contents, myocardial cross-section area (CSA), collagen volume fraction (CVF) and perivascular circumferential collagen area (PVCA) compared to the hypertensive model group. It also reduced the serum content of Hyp while increased BH4 levels in cardiac tissue. In addition, the expressions of Nox-2, P-JNK and P-p38MAPK were all suppressed compared to the hypertensive model group. Moreover, treatment with XJEK improved endothelial dysfunction (ED) manifested by promoting eNOS activities and enhancing the NO activity in serum.

Conclusion

The results of the present study show that XJEK attenuates 2K1C-induced hypertension in rats, which confirms our hypothesis that XJEK has an anti-hypertensive and cardiovascular remodeling effect via attenuation of cardiac remodeling and improvement of endothelial dysfunction and oxidative stress.     

葛根素对高血压大鼠血小板功能和心脏重塑影响的实验研究

目的研究葛根素对自发性高血压大鼠(SHR)血小板游离钙浓度、血小板聚集率和心脏重塑功能的影响。方法18只10月龄伴有左心室肥厚(LVH)的SHR随机分为葛根素组、福辛普利组和生理盐水组(NS组),每组6只。进行为期8周的干预治疗,观察其对SHR收缩压、心率、左心室肥厚指数、血小板胞浆游离钙和血小板聚集率的影响。结果SHR的收缩压、左心室肥厚指数、血小板胞浆游离钙浓度和血小板聚集率均显著高于同龄Wistar大鼠(P<0.01)。血小板胞浆游离钙浓度和血小板聚集率与左心室肥厚指数呈显著正相关(P均<0.01)。与NS组比较,2药均能显著降低左心室肥厚指数、血小板胞浆游离钙浓度和血小板聚集率(P均<0.01)。结论血小板内钙代谢异常和血小板聚集率可能在SHR心脏重塑中起重要作用。葛根素能显著降低SHR的血小板胞浆游离钙浓度和血小板聚集率,从而改善SHR心脏重塑。