宫内窘迫新生儿脐动脉血激活素A的变化及其临床意义

目的探讨宫内窘迫新生儿脐动脉血激活素A(ACT A)的变化及其临床意义。方法采用生物素-亲和素酶联免疫吸附试验检测40例正常妊娠对照组及35例胎儿宫内窘迫孕妇的新生儿脐动脉血ACT A水平,同时行脐动脉血血气分析。结果宫内窘迫孕妇组新生儿脐动脉血ACTA水平为(1235.89±178.78)ng/L,对照组为(627.28±75.24)ng/L,二组比较有显著性差异(P<0.05);脐动脉血血气分析,胎儿宫内窘迫组pH、p(O2)、碱剩余(BE)低于对照组,二组间比较有显著性差异(Pa<0.05),而p(CO2)高于对照组,二组间比较有显著性差异(P<0.05);胎儿宫内窘迫组新生儿脐动脉血ACTA水平与pH、p(O2)、BE呈负相关(r=-0.849,-0884,-0.817Pa<0.05);与脐动脉血p(CO2)呈显著正相关(r=0.835P<0.05)。结论胎儿宫内窘迫孕妇脐动脉血ACT A水平明显增加,且和脐动脉血气有明显的相关性,可作为一项新的临床指标预测胎儿宫内窘迫。     

扶正化瘀方含药血清对肝星状细胞activinA/smad信号通路活化的影响

目的　探讨扶正化瘀方含药血清对肝星状细胞（HSC）激活素A（activinA）/smad信号通路活化的影响。方法　20只SD大鼠按照随机数字表法分为对照组及扶正化瘀（Fzhy）-低、中、高剂量含药血清组，每组5只，分别以蒸馏水，0.75、1.5、3.0 g/kg扶正化瘀溶液（扶正化瘀胶囊药物粉末与蒸馏水配制）灌胃1次/d，连续3 d，取血制备空白血清（对照组）和含药血清。以大鼠HSC-T6细胞为研究对象，分别用5%、10%、20%体积分数的各组含药血清培养细胞。CCK-8检测细胞存活率，选取细胞存活率在50%左右的体积分数重新分为对照组及Fzhy-低、中、高剂量组。流式细胞术检测细胞周期及凋亡率、线粒体膜电位变化和活性氧（ROS）水平；实时荧光定量聚合酶链反应检测细胞中activinA、smad3、samd7、核因子（NF）-κB的mRNA水平；蛋白质印迹法检测细胞中activinⅡA受体（ActRⅡA）、smad3、NF-κB p65、胱天蛋白酶（caspase）-3的蛋白水平。结果　各扶正化瘀含药血清组的细胞存活率均低于对照组（P＜0.05），选择体积分数为10%的含药血清进行后续实验。对照组和各扶正化瘀方含药血清组细胞周期和凋亡率差异均无统计学意义。对照组及Fzhy-低、中、高剂量组细胞内ROS水平及线粒体膜电位水平降低比例逐次升高（P＜0.05）。与对照组比较，Fzhy-中、高剂量组smad3 mRNA表达水平降低，smad7 mRNA升高，Fzhy-低、中、高剂量组NF-κB、activinA mRNA，smad3、NF-κB p65、ActRⅡA蛋白表达水平降低，Fzhy-低剂量组、中剂量组caspase-3蛋白表达水平升高（P＜0.05）；与Fzhy-低剂量组相比，Fzhy-中、高剂量组smad3 mRNA表达水平降低，Fzhy-中剂量组activinA及smad7 mRNA升高（P＜0.05）。结论　扶正化瘀方含药血清可通过影响HSC-T6细胞增殖、参与细胞的氧化应激以及调节细胞activinA/smad信号转导通路来实现抗纤维化作用。     

Cellular and molecular changes that predispose skin in chronic spinal cord injury to pressure ulcer formation

Patients with spinal cord injury have a predisposition to develop pressure ulcers. Specific characteristics of the patients'' skin potentially involved have not yet been identified. The purpose of this investigation was to determine whether loss of neuronal control affects cellular and molecular homeostasis in the skin. Intact afflicted skin, wound edge of pressure ulcers, and control skin were analysed. Platelets, transforming growth factor‐β1, and activin A were identified by immunohistochemistry. Transforming growth factor‐β‐like activity was determined by bioassay, and gene expression by DNA microarray analysis or RT‐PCR. In afflicted skin, enhanced platelet extravasation was detected. Transforming growth factor‐β1 and activin A accumulated in the dermal‐epidermal junction zone. Transforming growth factor‐β‐like activity and activin A expression were increased in intact afflicted skin (compared to control skin) and were further enhanced in pressure ulcers. In vitro, activity was generated by fibroblast‐epithelial cell interactions, which also induced activin A. Thus, loss of neuronal control in spinal cord injury appears to trigger inappropriate wound healing processes in the patients'' skin. Plasma leakage and increased transforming growth factor‐β‐like activity combined with shear forces potentially enhance the risk for pressure ulcer formation.     

激活素A及抑制素A与子痫前期的相关性

目的探讨子痫前期病人血清抑制素A和激活素A的水平变化及其与病情的关系。方法采用酶联免疫分析法(ELISA),检测了40例子痫前期病人(子痫前期组,包括轻度20例,重度20例)及40例正常妊娠妇女(正常妊娠组)的血清抑制素A和激活素A水平。结果子痫前期组病人血清抑制素A、激活素A水平均高于正常妊娠组,差异有统计学意义(t=69.93、30.12,P<0.01);其中重度子痫前期病人血清抑制素A、激活素A水平高于轻度子痫前期病人,差异有统计学意义(t=43.88、18.84,P<0.01)。两组病人血清抑制素A与激活素A水平呈正相关(r=0.59、0.52,P<0.01);子痫前期组病人血清抑制素A、激活素A水平与24 h尿蛋白含量呈显著正相关(r=0.76、0.56,P<0.01)。重度子痫前期伴胎儿生长受限(FGR)与不伴FGR病人血清抑制素A、激活素A水平差异无统计学意义(P>0.05)。结论子痫前期病人血清抑制素A、激活素A水平较正常妊娠妇女显著升高,且与子痫前期病情进展关系密切。     

激活素A与肝纤维化的关系

目的探讨慢性乙型肝炎(CHB)患者血清激活素A(activin A,ACTA)与肝细胞损伤、肝纤维组织增生的关系。方法采用酶联免疫吸附试验(ELISA)测定118例慢性乙肝患者(其中慢性轻度35例,中度30例,重度28例,肝硬化25例)血清ACTA及透明质酸(HA)、四型胶原(ⅣC)、层粘连蛋白(LN)含量,并分析其相关性。其中35例进行肝活检,行苏木素染色(HE),应用多媒体彩色图文分析系统对肝内胶原纤维进行定量分析。同时测定肝功能(TBil、ALT、GLB),进行相关性分析。结果慢性乙肝轻、中、重度及肝硬化(LC)患者血清ACTA水平依次升高,明显高于对照组(P<0.01或P<0.05)。除慢性轻度组LN外,其他各组血清ACTA与HAI、VC、LN呈明显正相关(P<0.01或P<0.05)。ACTA与肝功能指标(TBil、ALT、GLB)明显正相关(P<0.01或P<0.05)。结论ACTA在慢性肝病纤维化发病机制中起重要作用。血清ACTA的检测可做为慢性乙肝患者肝纤维化程度和肝细胞受损程度的判断依据。     

Development of cell markers for the identification and expansion of islet progenitor cells

Diabetes mellitus results from the anatomical or functional loss of insulin-producing beta cells of the pancreas. Despite significant advances in current treatment, patients with diabetes still do not maintain optimal glucose levels and therefore face debilitating complications such as hypoglycemia, retinopathy or cardiovascular diseases later in life. Islet transplantation therefore holds great promise as an ultimate cure for diabetes. However, the shortage of availability of donor sources of islets for transplantation has largely hampered this therapy. In this respect, the use of alternative sources of islets such as the ex vivo culture and expansion and differentiation of functional endocrine cells for treating diabetes has been a major focus of diabetes research. The identity of the islet stem/progenitor cells has remained either elusive or at least equivocal because of the lack of cell markers for identification of these cells. Recent successes in studying the organogenesis of pancreas as well as in vitro islet progenitor cell identification studies have provided tremendous insight for the cell markers that are essential in the isolation and characterization of these cells prospectively both in vivo and in vitro. If we can identify the markers that will aid the isolation and purification of islet progenitor cells, or factors that determine pancreatic cell fate, we might be able to coerce them from turning into specific endocrine cells or pancreas in vitro. This article will focus on this subject and will review the latest achievements in the study of cell markers for islet progenitor cells.     

充血性心力衰竭患者激活素A、基质金属蛋白酶9及N端脑钠肽前体水平的变化及其临床意义

目的 探讨充血性心力衰竭(CHF)患者血浆激活素A(ACT-A)、基质金属蛋白酶9(MMP-9)和N端脑钠肽前体(NT-proBNP)水平变化及临床意义.方法 应用酶联免疫吸附法(ELISA)分别测定86例CHF患者治疗前后及30例正常人血浆ACT-A、MMP-9和NT proBNP水平,并进行统计学分析比较.结果 ①CHF组ACT-A、MMP 9和lgNT-proBNP水平分别为(2.94±1.44) μg/L、(260.01±88.23) μg/L和(5.51±1.73) ng/L明显高于对照组(1.03±0.27) μg/L、(80.51±28.66)μg/L和(4.11±0.16) ng/L(均P＜0.01);②心功能Ⅱ、Ⅲ、Ⅳ级组ACT-A分别为(1.72±0.25) μg/L、(2.33±0.51)μg/L及(4.78±0.78) μg/L,MMP-9水平分别为(142.60±50.43) μg/L、(225.14±33.03) μg/L及(310.27±75.77) μg/L,lgNT-proBNP水平分别为(4.67±0.35) ng/L、(5.48±1.07) ng/L及(5.91±1.47) ng/L,以上指标均为CHFⅢ级高于CHFⅡ级,CHFⅣ级高于Ⅱ级和Ⅲ级(均P＜0.01).③CHF组治疗后血浆ACT A、MMP-9和lgNT-proBNP水平分别为(2.17±0.79) μg/L、(184.50±52.40) μg/L和(4.39±0.87) ng/L显著低于治疗前水平(2.94±1.44) μg/L、(260.01±88.23) μg/L和(5.51±1.73) ng/L(均P＜0.01).④CHF组血浆ACT A、MMP-9与lgNT-proBNP呈正相关(r＝0.732、0.771,P＜0.05).结论 CHF患者血浆ACT-A、MMP-9和NT-proBNP水平较正常人显著升高,且这些指标随着心功能恶化而明显升高.对其血浆浓度的测定有助于CHF的早期诊断和分级.     

激活素A及其ⅡA型受体在小鼠肝损伤模型肝组织中的表达

目的：探讨激活素A及其ⅡA型受体在Con A诱导的小鼠肝损伤模型肝组织中的表达形式及其可能的作用。方法：小鼠尾静脉注射Con A（10 mg•kg^-1）,每周1次,连续4周,建立小鼠肝损伤模型（n=24）,另设正常对照组（n=24）,于末次注射后的24、72、120 及168 h,各组（n=6）分批检测小鼠血清酶变化及肝脏组织病理损伤程度,同时采用荧光定量RT-PCR法检测激活素A及其ⅡA型受体的表达水平。结果：在末次注射后72 h肝组织病理损伤最为严重,肝小叶结构紊乱,肝细胞索消失,细胞肿胀,呈气球样变,以后逐渐恢复;激活素A蛋白水平及其mRNA表达与其ⅡA型受体mRNA表达呈平行状态,于注射后72 h达高峰,与对照组比较差异具有显著性(P<0.05)。结论：激活素A与其Ⅱ A受体变化与肝组织病理损伤呈平行状态,提示激活素A可能参与了Con A诱导肝损伤模型小鼠的肝损伤。