B淋巴细胞刺激因子与系统性红斑狼疮

B淋巴细胞刺激因子（Blys）是肿瘤坏死因子配体超家族成员，可刺激B淋巴细胞增殖、分化及分泌抗体，对机体的免疫应答、尤其是体液免疫应答起着关键性作用。Blys缺陷或过量表达均可引起机体免疫失衡，诱发多种自身免疫性疾病。StysmRNA可能是SLE疾病活动性的一个有用的生物学标志，Blys拮抗剂为SLE的治疗带来新的研究方向。     

Prognostic Implications of Progressive Systemic Ventricular Dysfunction in Congenitally Corrected Transposition of Great Arteries

ObjectivesThe purpose of this study was to determine the risk factors for and prognostic implications of progressive right ventricular systolic dysfunction (RVD) in adults with congenitally corrected transposition of great arteries.BackgroundThere are no effective therapies for RVD; hence the need to identify and modify risk factors for progressive RVD.MethodsRV systolic function was assessed by using RV longitudinal strain (RV-LS). The first echocardiogram (baseline echocardiogram) and all subsequent annual echocardiograms performed within 5 years from the baseline echocardiogram were analyzed. Progressive RVD (temporal decline in RV-LS) was assessed as the average annual change in RV-LS within 5 years of imaging follow-up.ResultsOf 186 patients (mean age 40 ± 12 years), the RV-LS at baseline was –17% ± 4%, and the annual decline in RV-LS was –4% (95% CI: –6 to –2). The risk factors for progressive RVD were left ventricular (LV) systolic dysfunction, LV pacing, and systemic hypertension. Cardiovascular events (heart failure hospitalization, heart transplant, and death) occurred in 57 (27%) patients. Progressive RVD was associated with cardiovascular events, independent of RV systolic function at baseline. In subgroup analyses assessing impact of therapies (medical therapy, cardiac resynchronization therapy, and tricuspid valve replacement), only tricuspid valve replacement was associated with improvement in RV systolic function when performed before onset of RVD.ConclusionsPatients with congenitally corrected transposition of great arteries were at risk for progressive RVD, and the risk factors for progressive RVD were LV pacing, systemic hypertension, and concomitant LV dysfunction. Further studies are required to determine whether strict blood pressure control and early tricuspid valve replacement will prevent progressive RVD.     

Endothelial mechanotransduction, nitric oxide and vascular inflammation

Numerous aspects of vascular homeostasis are modulated by nitric oxide and reactive oxygen species (ROS). The production of these is dramatically influenced by mechanical forces imposed on the endothelium and vascular smooth muscle. In this review, we will discuss the effects of mechanical forces on the expression of the endothelial cell nitric oxide synthase, production of ROS and modulation of endothelial cell glutathione. We will also review data that exercise training in vivo has a similar effect as laminar shear on endothelial function and discuss the clinical relevance of these basic findings.     

肝素结合表皮生长因子在高血压大鼠心肌表达及氯沙坦对其影响

目的探讨肝素结合表皮生长因子(HB-EGF)在自发高血压大鼠(SHR)心肌表达情况及氯沙坦对其影响。方法取16只8周龄自发性高血压大鼠,随机分为两组,每组8只:氯沙坦干预组,给予氯沙坦30mg/kg·d溶于饮水灌胃治疗;SHR阳性对照组给予正常饮水。另有8只同龄同源雄性正常血压Wistar-kyoto大鼠(WKY)组作为正常对照组。实验周期12周。观察血压、左室重量/体重(LVW/BW);逆转录多聚酶链反应(RT-PCR)和免疫组化实验检测各组大鼠HB-EGFmRNA的表达情况。结果正常对照组和氯沙坦组血压和LVW/BW均底于SHR阳性对照组;SHR阳性对照组HB-EGFmRNA表达均高于正常对照组和氯沙坦组;氯沙坦组HB-EGFmRNA表达高于正常对照组。结论肝素结合表皮生长因子在自发高血压大鼠组表达明显增加而氯沙坦能部分阻断HB-EGFmRNA的表达提示HB-EGFmRNA可能在高血压发生发展过程中起了一定作用。     

Expression of gamma-aminobutyric acid A receptor subunits aα_1,β_1,γ_2 mRNA in rats with hepatic encephalopathy

AIM:To investigate the mRNA expression of gamma-aminobutyric acid A (GABAA) receptor subunits α1,β1,γ2 in different parts of the brain of rats with hepatic encephalopathy. METHODS: Twelve adult male Sprague-Dawley rats were randomly divided into two groups: (1) hepatic encephalopathy model group (n=6),which was induced by intraperitoneal injection of thioacetamide (TAA,350 mg/kg) for three consecutive days; (2) control group (n=6), in which the rats were treated with same dose of normal saline solution. After the freeze slice of cerebrum was made, in situ hybridization was used to detect the mRNA of GABAA receptor subunits α1, β1, and γ2 in rat cerebral cortex, basal nuclei, substantia nigra and hippocampi. Image data were collected and analyzed quantitatively by QWin550CW model image signal gather and analysis system. RESULTS:In rats with hepatic encephalopathy,mRNA expression levels of GABAA receptor subunits α1,β1 increased significantly in basal nuclei,substantia nigra pars compacta,substantia nigra pars reticularis and hippocampi (144.7±15.67/184.14±4.41, 60.61±33.66/113.07±32.44, 87.71±21.25/128.40±18.85, 122.34±5.56/161.60±4.56, 123.29±5.21/140.65±4.15, 123.40±4.42/140.09±4.52, 124.76±4.18/140.09±4.12, 141.62±15.09/182.80±5.20, 69.13±30.74/134.21±43.76, 87.87±25.16/151.01±19.49, 122.14±6.30 /162.33±3.92, 122.81±5.09/137.19±7.12, 123.00±4.63/138.11±5.92, 125.75±2.43/138.81±6.10, P<0.01), but did not change in the cerebral cortex compared to the control group.Similar changes were found in the mRNA expression levels of GABAA receptor subunit γ2, which increased significantly in basal nuclei,substantia nigra pars compacta,substantia nigra pars reticularis (136.81±26.41/167.97±16.23,51.00±36.14/113.18±36.52, 86.35±20.30/ 126.90±19.74, P<0.01), CA1 of hippocampal (162.15±9.05/178.62±6.45,P<0.05),and no changes were found in the cerebral cortex and CA2, CA3, CA4 of hippocampi. CONCLUSION:In rats with hepatic encephalopathy, mRNA expression levels of GABAA receptor subunits α1,β1,γ2 increase significantly in basal nuclei,substantia nigra and hippocampi,suggesting that the changes of mRNA expression levels in GABAA receptor subunits may contribute to the pathogenesis of hepatic encephalopathy.     

Seasonal change in luteinizing hormone subunit mRNA in Japanese quail and effects of short daylength and low temperature

Changes in pituitary mRNA levels of LHbeta-subunit (LHbeta) and glycoprotein hormone alpha-subunit (common alpha) were investigated in male Japanese quail under natural and laboratory conditions to clarify the mechanisms of seasonal regulation of luteinizing hormone (LH) secretion. In Experiment 1, birds were kept in outdoor cages under natural conditions from August for 12 months. Both LHbeta and common alpha mRNA levels decreased rapidly from August to September, and after a period of low levels from October through January, they began to increase in February and continued to increase until July. There were more pronounced seasonal changes in testicular weight and cloacal protrusion width with large decreases from August to September and increases from March to May. In Experiment 2, birds were kept on laboratory conditions and transferred from long to short daylengths at 20 or 9 degrees C and held for 14 days. Although common alpha mRNA levels, plasma LH concentrations, testicular weight, and cloacal protrusion area decreased on short days without low temperatures, levels of LHbeta mRNA did not change. Short daylengths combined with low temperatures induced testicular regression and caused decrease in all the parameters measured. Low temperatures under long days did not induce any change in the parameters significantly. These results suggest that (1) synthesis as well as secretion of LH is regulated seasonally, (2) short daylength does not suppress LH synthesis completely unless combined with low ambient temperature, and (3) the effect of photoperiod on the endocrine system regulating LH secretion is predominant over the effect of ambient temperature but ambient temperature acts as an environmental cue to terminate reproductive activities at late summer to early autumn in Japanese quail.     

Recovery of insulin sensitivity and Slc2a4 mRNA expression depend on T3 hormone during refeeding

Objective

GLUT4 protein, encoded by the Slc2a4 gene, plays a key role in muscle glucose uptake, and its expression decreases in muscles under insulin resistance. Slc2a4/GLUT4 decreases with fasting and rapidly increases with refeeding and the same occurs to plasma glucose, amino acids, insulin and T3. Thus, they might be potential regulators of the Slc2a4 gene, which makes them promising targets for strategies to improve GLUT4 expression. Herein, we investigate the role of metabolic–hormonal parameters triggered by refeeding upon the Slc2a4 expression.

Materials/Methods

Plasma glucose/insulin/T3, and gastrocnemius Slc2a4 mRNA contents were measured in rats studied at the end of 48-h fasting, and subsequently at: i) 2–4 h after spontaneous refeeding; ii) 2–4 h after T3 injection, without refeeding; and iii) 0.5–2 h after intravenous infusion of insulin, insulin + glucose and insulin + amino acids, without refeeding.

Results

Refeeding increased plasma glucose/insulin/T3 and muscle Slc2a4 mRNA, reverting insulin resistance. Post-fasting infusions surprisingly induced a further Slc2a4 mRNA decrease (~ 20%, P < 0.05 vs. fasting), but T3 injection induced a ~ 2-fold increase in Slc2a4 mRNA, 2–4 h later (P < 0.001). Moreover, T3 increased glycemia and insulinemia to the 2 h-refed rats levels, suggesting that T3 elevation is a key factor to the mechanisms of metabolic balance during refeeding.

Conclusions

Refeeding induces a rapid increase in muscle Slc2a4 expression, not associated with increased plasma glucose, insulin or amino acids, but highly correlated to increased plasma T3 concentration. This result points out T3 hormone as a powerful Slc2a4 enhancer, an effect that may be acutely explored in situations of insulin resistance.     

Reproductive actions of prolactin mediated through short and long receptor isoforms

Prolactin (PRL) is a polypeptide hormone with a wide range of physiological functions, and is critical for female reproduction. PRL exerts its action by binding to membrane bound receptor isoforms broadly classified as the long form and the short form receptors. Both receptor isoforms are highly expressed in the ovary as well as in the uterus. Although signaling through the long form is believed to be more predominant, it remains unclear whether activation of this isoform alone is sufficient to support reproductive functions or whether both types of receptor are required. The generation of transgenic mice selectively expressing either the short or the long form of PRL receptor has provided insight into the differential signaling mechanisms and physiological functions of these receptors. This review describes the essential finding that both long and short receptor isoforms are crucial for ovarian functions and female fertility, and highlights novel mechanisms of action for these receptors.