Morphological,Functional, and Tissue Characterization of Silent Myocardial Involvement in Patients With Primary Biliary Cholangitis

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High plasma microfibrillar-associated protein 4 is associated with reduced surgical repair in abdominal aortic aneurysms

ObjectiveIdentifying biomarkers for abdominal aortic aneurysms (AAA) could prove beneficial in prognosis of AAA and thus the selection for treatment. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein that is highly expressed in aorta. MFAP4 is involved in several tissue remodeling-related diseases. We aimed to investigate the potential role of plasma MFAP4 (pMFAP4) as a biomarker of AAA.MethodsPlasma samples and data were obtained for 504 male AAA patients and 188 controls in the Viborg Vascular (VIVA) screening trial. The pMFAP4 levels were measured by Alphalisa. The Mann-Whitney U test assessed differences in pMFAP4 levels between the presence and absence of different exposures of interest. The correlation between pMFAP4 and aorta growth rate were investigated through spearman's correlation analysis. Immunohistochemistry and multiple logistic regression adjusted for potential confounders assessed the association between pMFAP4 and AAA. Multiple linear regression assessed the correlation between pMFAP4 and aorta growth rate. Cox regression and competing risk regression were used to investigate the correlation between AAA patients with upper tertile pMFAP4 and the risk of undergoing later surgical repair.ResultsA significant negative correlation between pMFAP4 and aorta growth rate was observed using spearman's correlation analysis (ρ = −0.14; P = .0074). However, this finding did not reach significance when applying multiple linear regression. A tendency of decreased pMFAP4 was observed in AAA using immunohistochemistry. Competing risk regression adjusted for potential confounders indicated that patients with upper tertile pMFAP4 had a hazard ratio of 0.51 (P = .001) for risk of undergoing later surgical repair.ConclusionsHigh levels of pMFAP4 are associated with a decreased likelihood of receiving surgical repair in AAA. This observation warrants confirmation in an independent cohort.     

异丙酚对小鼠海马脑片细胞外信号调节激酶ERK1/2磷酸化水平的影响

目的 观察异丙酚对小鼠海马脑片细胞外信号调节激酶ERK1／2磷酸化水平的影响。方法BALB／C小鼠，体重18～22g，雌雄不拘，迅速断头取脑，取海马用震动切片机切成450μm厚的脑片。量效实验随机将脑片分为空白对照组（C组）及不同浓度异丙酚组[10^-4mmol／L（P1组）、10^-5mmol／L（P2组）、10^-6mmol／L（P3组）、10^-7mmol／L（P4组）、10^-8mmol／L（P5组）、10^-8mmol／L（P6组）]；分别以不同浓度的异丙酚36℃恒温孵育海马脑片1h。时效实验应用5μmol／L异丙酚孵育脑片，分别于孵育即刻、1、2、5、7、9、12、15、30、60min取出脑片；取5μmol／L异丙酚孵育5min后的部分脑片，以人工脑脊液洗出异丙酚，分别于洗出2、4、7、10、25min取出脑片。应用SDS-PAGE和Westem blot生化技术及Gel Doc凝胶成像系统半定量检测小鼠海马p-ERKI／2水平。结果 异丙酚能降低ERK1／2磷酸化水平，降低呈时间、浓度依赖性（P〈0．05）。随异丙酚孵育5min后洗出时间延长，ERK1／2的磷酸化水平逐渐恢复，但洗出25min时仍明显低于药物处理前水平（P〈0．01）。结论 异丙酚能显著地抑制小鼠海马脑片细胞外信号调节激酶ERK1／2磷酸化水平。     

An analysis of astrocytic cell lines with different abilities to promote axon growth

The adult mammalian central nervous system (CNS) lacks the capacity to support axonal regeneration. There is increasing evidence to suggest that astrocytes, the major glial population in the CNS, may possess both axon-growth promoting and axon-growth inhibitory properties and the latter may contribute to the poor regenerative capacity of the CNS. In order to examine the molecular differences between axon-growth permissive and axon-growth inhibitory astrocytes, a panel of astrocyte cell lines exhibiting a range of axon-growth promoting properties was generated and analysed. No clear correlation was found between the axon-growth promoting properties of these astrocyte cell lines with: (i) the expression of known neurite-outgrowth promoting molecules such as laminin, fibronectin andN-cadherin; (ii) the expression of known inhibitory molecules such tenascin and chondroitin sulphate proteoglycan; (iii) plasminogen activator and plasminogen activator inhibitor activity; and (iv) growth cone collapsing activity. EM studies on aggregates formed from astrocyte cell lines, however, revealed the presence of an abundance of extracellular matrix material associated with the more inhibitory astrocyte cell lines. When matrix deposited by astrocyte cell lines was assessed for axon-growth promoting activity, matrix from permissive lines was found to be a good substrate, whereas matrix from the inhibitory astrocyte lines was a poor substrate for neuritic growth. Our findings, taken together, suggest that the functional differences between the permissive and the inhibitory astrocyte cell lines reside largely with the ECM.     

重组人血小板源性生长因子增加细胞外信号调节激酶磷酸化促进糖尿病大鼠全层皮肤缺损创面愈合

目的 在体观察重组人血小板源性生长因子（recombinant human platelet—derived growth factor，rhPDGF）促进糖尿病大鼠全层皮肤缺损创面修复可能涉及的细胞和分子机制，研究其可能涉及的信号通路。方法 26只糖尿病大鼠，每只动物背部制备4个全层皮肤缺损创面，选取其中52个创面，随机分成3组，即对照组，创面自然愈合；rhPDGF治疗组，创面rhPDGF用量为7．0μg／cm^2；赋形剂组，创面用等量赋形剂凝胶。观察治疗后3、7和14d创面肉芽形成、胶原沉积、再上皮化速率以及炎性细胞浸润情况，并采用免疫荧光和免疫组织化学技术观察创面周围和创面修复细胞内细胞外信号调节激酶1／2（extracellular signal—regulated kinase1／2，ERK1／2）磷酸化和增殖细胞核抗原（proliferative cell nuclear antigen，PCNA）的表达。结果 组织学观察，rhPDGF治疗组创面可见大量炎性细胞浸润，毛细血管胚芽及成纤维细胞明显多于另两组（P〈0．05）；胶原沉积明显，肉芽组织生长活跃，创面收缩显著，与对照组比较差异有统计学意义（P〈0．05）。免疫学研究显示，应用rhPDGF7～14d后，rhPDGF治疗组ERK1／2明显强于对照组和赋形剂组（P〈0．05）；且损伤后3～7d rhPDGF治疗组修复细胞PCNA的表达明显高于对照组和赋形剂组（P〈0．05）。结论 rhPDGF促糖尿病大鼠刨面愈合的作用部分是通过ERK1／2信号通路的磷酸化来完成的。     

Stress und Grundregulation – Wirkungsweise von Akupunktur und Neuraltherapie

Stress is a general reaction to any burden on the body. If such a process becomes chronic, stress-based diseases develop which are hard to treat. The stress cycle in the hypothalamus-hypophysis-suprarenal glands disturbs the bio-psycho-social circuit, which is in a feedback loop with controlled and uncontrolled stress converting processes. This is coupled with the reactivity of the extracellular matrix (ECM) embedded in this circuit. Two “breaks” are installed in the ECM to keep stress reactions under control: The non neuronal acetylcholin system (NNAChS) and the system of endogenous endocannabinoids. Both systems have a limiting effect on pathological increased sympathetic effects raised by stress. Acupuncture stimulates the parasympathicus and NNAChS while neural therapy augments the endocannabinoid system, resulting in slower sympathetic actions.     

尿转化生长因子-β1和细胞外基质在慢性肾小球肾病中的变化

目的：探讨尿中转化生长因子-β1（TGF-β1）和细胞外基质（ECM）在各种慢性肾小球肾病患者中的变化及其临床意义。方法：将105例慢性肾小球患者进行临床和病理分组,采用酶联免疫吸附试验（ELISA）分别检测各组的尿TGF-β1水平,同时采用放射免疫分析法（RIA）检测尿中的各种ECM,所有检测值均用尿肌酐（Cr）浓度进行校正。结果：在不同临床分组中,尿TGF-β1/Cr和LN/Cr、PCⅢ/Cr、Ⅳ-C/Cr水平明显高于对照组（P〈0.05）,尿HA/Cr水平则在Ⅲ、Ⅳ组中出现下降。而在不同的病理分组中,肾小球轻微病变（GML）组尿中TGF-β1、ECM与对照组比较无统计学意义,其他各病理分组则出现不同的变化。相关性分析尿TGF-β1/Cr与LN/Cr、PCⅢ/Cr、Ⅳ-C/Cr正相关,与HA/Cr无相关性。结论：通过尿TGF-β1和ECM在慢性肾小球肾病患者中的联合检测,对评价慢性肾小球肾病的进展和预后判断提供一定的临床价值。     

氯沙坦调节两肾一夹型高血压大鼠血管重塑及其与细胞外信号调节激酶1/2的关系

为探讨特异性血管紧张素Ⅱ受体 1阻断剂氯沙坦调节高血压血管重塑与细胞外信号调节激酶的关系 ,本文采用两肾一夹型高血压大鼠为动物模型 ,术后第 2、4、6周测血压 ,6周后处死大鼠称心脏重量 ,取胸主动脉和肠系膜动脉作形态学观察和计算机图像分析 ,免疫印迹方法检测主动脉中磷酸化细胞外信号调节激酶及总细胞外信号调节激酶的表达。结果发现 ,与假手术对照组相比 ,模型组大鼠血压和心脏与体重之比分别增加 5 0 %和 48%(P均 <0 .0 1) ,主动脉和肠系膜动脉的内径与中膜厚度之比明显减少 (分别为 7.10± 0 .5 9比 9.2 4± 1.17,6.0 0± 0 .89比 8.96± 1.2 3 ) ,中膜厚度明显增加 (分别为 119.47± 10 .77μm比 91.5 5± 14.45 μm ,49.60± 1.0 4μm比 3 7.0 1± 4.85 μm ,P均 <0 .0 5 ) ,主动脉中磷酸化细胞外信号调节激酶的表达显著增强 ;氯沙坦治疗后 ,血压、心脏与体重之比分别下降到 13 2± 9mmHg、0 .3 2± 0 .0 3 (P均 <0 .0 5 ) ,主动脉和肠系膜动脉的内径与中膜厚度之比明显增加 ,中膜厚度明显减小 ,并下调主动脉中磷酸化细胞外信号调节激酶的表达。提示氯沙坦可明显改善两肾一夹型高血压大鼠的血管重塑 ,这种调节可能是通过细胞外信号调节激酶信号途经发挥作用的     

慢性束缚应激对大鼠行为及前额叶皮质细胞外信号调节激酶磷酸化的影响

目的 探讨慢性束缚应激模型大鼠的行为及前额叶皮质中磷酸化细胞外信号调节激酶（ERK1／2）表达的变化。方法 将雄性SD大鼠随机分为正常对照组和束缚应激组，每组8只。将束缚应激组大鼠放入特制的束缚器中限制其活动，6k／d，连续21d。比较应激前后大鼠旷场行为和Morris水迷宫行为学的改变，用蛋白免疫印迹技术和免疫组织化学方法观察应激后大鼠前额叶皮质P—ERK1／2表达的变化，并与正常对照组比较。结果 （1）行为学改变：应激后，束缚应激组大鼠的水平活动度[（4265±864）mm]少于正常对照组[（8562±502）mm]，中央停留时间[（39．1±4．3）s]长于正常对照组[（24．6±1．6）s]，均P〈0．01；束缚应激组大鼠在Morris水迷宫实验的目标象限活动时间[（57．2±1．7）s]和穿越站台次数[（2．0±0．8）次]均少于正常对照组[分别为（70．7±3．6）s和（6．2±1．0）次；均P〈0．01]。（2）p-ERK1／2蛋白水平：应激后束缚应激组吸光度（A）值[（0．767±0．006）]低于正常对照组[（0．813±0．015）；P〈0．05]。（3）p-ERK1／2阳性细胞数：应激后束缚应激组[（76±5）个]少于正常对照组[（110±14）个；P〈0．05]，且树突染色浅淡。结论 慢性心理应激明显影响动物的活动度和记忆能力；前额叶皮质中p-ERK1／2表达的减少，提示ERK信号转导通路可能参与了应激发生的机制。