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。     

Chemokine-like factor 1, a novel cytokine, contributes to airway damage, remodeling and pulmonary fibrosis

Background Chemokine-like factor 1 (CKLF1) was recently identified as a novel cytokine. The fulllength CKLF1 cDNA contains 530 bp encoding 99 amino acid residues with a CC motif similar to that of other CC family chemokines. Recombinant CKLF1 exhibits chemotactic activity on leucocytes and stimulates proliferation of murine skeletal muscle cells. We questioned whether CKLF1 could be involved in the pathogenesis of inflammation and proliferation in the lung. Therefore we used efficient in vivo gene delivery method to investigate the biological effect of CKLF1 in the murine lung. Methods CKLFl-expressing plasmid, pCDI-CKLF1, was constructed and injected into the skeletal muscles followed by electroporation. Lung tissues were obtained at the end of week 1,2,3 and 4 respectively after injection. The pathological changes in the lungs were observed by light microscope. Results A single intramuscular injection of CKLF1 plasmid DNA into BALB/c mice caused dramatic pathological changes in the lungs of treated mice. These changes included peribronchial leukocyte infiltration, epithelial shedding, collagen deposition, proliferation of bronchial smooth muscle cells and fibrosis of the lung. Conclusions The sustained morphological abnormalities of the bronchial and bronchiolar wall, the acute pneumonitis and interstitial pulmonary fibrosis induced by CKLF1 were similar to phenomena observed in chronic persistent asthma, acute respiratory distress syndrome and severe acute respiratory syndrome. These data suggest that CKLF1 may play an important role in the pathogenesis of these important diseases and the study also implies that gene electro-transfer in vivo could serve as a valuable approach for evaluating the function of a novel gene in animals.     

PPAR-α/γ激动剂对代谢综合征大鼠模型心室重构中MMP-9表达和TGF-β/Smads通路的影响

目的探讨PPAR-α／γ动剂对代谢综合征（Metabolic syndrome,MS）大鼠模型心室重构中MMP-9表达和TGF-βSmads通路的影响及意义。方法60％果糖饮食喂养雄性sD大鼠构建MS大鼠模型并随机分组：模型对照组（MC组,n=10）、非诺贝特组（FEN组,n=11）、吡恪列酮组（PIO组,n=10）、非诺贝特±匹格列酮组（FEN＋PIO组,n=11）,正常对照组mc组,n=6）。NC组大鼠用普通标准饲料喂养,FEN组和PIO组大鼠分别加用非诺贝特30mg／（kg·d）及吡格列酮3mg／（kg·d）灌胃;FEN＋PIO组大鼠加非诺贝特30mg／（kg·d）和吡格列酮3mg／（kg·d）灌胃,干预4周后RT-PCR方法检测PPAR-edymRNA水平,免疫组化方法检测MMP-9和TGF-β1蛋白表达。结果MC组PPAR-α／γmRNA的结果均低于NC组,差异具有统计学意义（P〈0．05）。FEN组PPAR—ccmRNA（0．59±0．03）和PPAR-ymRNA（0．61±0．03）均高于MC组,低于NC组,差异具有统计学意义（P〈0．05）;PIO组PPAR-α（0．57±0．04）和PPAR-TmRNA（0．54±0．02）均低于NC组,且低于MC组,具有统计学意义（P〈0．05）;FEN±PIO组PPAR-amRNA（0．63±0．02）和PPAR-ymRNA（0．67±0．03）均高于MC组,差异具有统计学意义（P〈0．05）;MMP-9和TGF-β1在各组大鼠心肌均有表达。与NC组大鼠比较,MC组、FEN组、PIO组和FEN±PIO组大鼠心肌表达MMP-9和TGF-β1／Smads蛋白明显增强,差异具有统计学意义（P〈0．05）;与MC组比较,FEN组、PIO组、FEN±PIO组大鼠心肌表达MMP-9和TGF-β1／Smads蛋白均减弱,差异具有统计学意义（P〈0．05）;FEN±PIO组大鼠心肌表达MMP-9OD值（0．43±0．04）低于FEN组和PIO组,差异具有统计学意义（P〈0．05）。结论FEN和PIO均上调了PPAR-α／γmRNA表达、使TGF-β1和MMP-9蛋白明显下降,对心室重构改善有明显的意义,其可能通过TGF-β／smads通路发挥作用。     

电子病历结构化模型分析与设计

探讨了结构化电子病历中模板设计思想,该模型通过不同层次对象的组合来构成病历,能适应各种病历的结构化处理,病历数据结构化程度高、数据粒度细。该模型将提高医生的工作效率和病历质量,为临床科研和数据分析提供有效手段。     

NSF-Based Analysis of the Structural Stressing State of Trussed Steel and a Concrete Box Girder

This paper analyses the characteristics of the mechanical behavior of a trussed steel and concrete box beam under bending conditions based on the structural stressing state theory and the numerical shape function method. Firstly, the parametric generalized strain energy density was introduced to characterize the structural stressing state of trussed steel stud concrete box girders, and the strain energy density sum was plotted. Then the Mann-Kendall criterion was used to discriminate the leap point of the curve change and to redefine the structural failure load. By analyzing the strain and displacement, the existence of a sudden change in the structural response during the load-bearing process was again demonstrated. Afterwards, the numerical shape function method was used to extend the strain data, and further in-depth analyses of strain/stress fields and internal forces were carried out to show in detail the working characteristics of each under load. Through an in-depth analysis from different angles, the rationality of updating the failure load was verified. Finally, the effects of different structure parameters on the evolution of the structural stresses of the members were analyzed in a transversal comparison. The analysis results of the stress state of a steel-concrete truss structure reveal the working behavior characteristics of a steel-concrete truss structure from a new angle, which provides a reference for the design of a steel-concrete truss structure in the future.     

基于内在驱动因素模型的医院绩效方案评价

目的：从绩效评价系统的内在驱动力因素入手,探索评价绩效方案的方法,辅助医院建立和完善绩效评价体制。方法以某医院为研究对象,通过因子分析验证文献研究,建立评价模型并做模糊综合评价。结果正规化、目标设置、公平感知是评价绩效方案有效性的三个维度;经过计算和检验,该医院运行的绩效方案评价比较好。结论兼顾良好公平性,合理目标设置,适度正规化的绩效制度,能有效提高医疗效率,促进医疗资源的优化配置;助推医院完成战略式发展,最终实现两个效益。     

蛋白激酶C亚型在血管外膜成纤维细胞中的表达

目的了解蛋白激酶C（PKC）亚型在血管外膜成纤维细胞中的表达情况。方法用β1-转化生长因子（TGF-1β）可将AF诱导为MF,用免疫组化法可以鉴定转化是否成功。根据文献报道,蛋白激酶C的许多亚型在AF与MF中的表达量往往差异有统计学意义。实验选取PKC-ε、PKC-δ、PKC-ζ作为研究对象用定量PCR的方法,比较它们在AF和MF中表达的差异。结果 PKC-ε、PKC-ζ的表达在MF中明显高于AF,而PKC-δ的表达差异无统计学意义。结论本实验为进一步研究PKC家族在血管外膜成纤维细胞表型转化中的作用打下基础。