缬沙坦对小鼠足细胞GPSD核心蛋白在高糖环境下表达的影响

目的通过观察缬沙坦体外干预高糖环境培养的小鼠足细胞nephrin、podocin和CD2AP的表达,探讨RAS抑制剂治疗糖尿病肾病蛋白尿的机制。方法用不同浓度的缬沙坦干预高糖(25mmol/L的葡萄糖)培养24h后的小鼠足细胞,以RT-PCR方法检测干预前后足细胞nephrin、podocin和CD2AP mRNA的表达水平;以间接免疫荧光法检测2×10-5mol/L缬沙坦干预后nephrin、podocin蛋白的表达。结果①与对照组相比,高糖诱导的足细胞nephrin、podocin和CD2AP mRNA表达显著减弱(P<0.01);②缬沙坦能显著上调高糖诱导的足细胞nephrin、podocin和CD2AP mRNA的表达(P<0.05或P<0.01);③2×10-5mol/L缬沙坦能显著上调高糖对足细胞nephrin和podocin(P<0.05)蛋白表达的抑制。结论缬沙坦显著上调髙糖诱导的足细胞nephrin、podocin和CD2AP的表达,可能是其独立于降压作用以外的降低糖尿病肾病蛋白尿的机制之一。     

复方益肾胶囊对糖尿病大鼠肾组织中TNF-α表达的实验研究

目的：研究复方益肾胶囊对糖尿病肾病保护作用。方法：将雄性Wistar大鼠手术切除右肾后合并注射小剂量链脲佐菌素诱导糖尿病大鼠模型;应用免疫组化SABC法检测左肾TNF-α的表达。结果：TNF-α在正常肾组织中呈弱阳性表达,在DN组表达明显增强（与正常对照组相比,P〈0．01））,复方益肾胶囊高剂量组大鼠肾组织TNF-α表达与模型组比较明显降低（P〈0．05）,且与西药对照组效果接近（P〉0．05）。结论：复方益肾胶囊能一定程度下调肾组织TNF-α的表达,有利于改善DN大鼠肾小球滤过率以及控制血糖,并阻断糖尿病大鼠肾脏病变发展的作用。     

Systematic Reviews Published in the April 2013 Issue of the Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD and monthly online (http://www.thecochranelibrary.com). The April 2013 issue (2nd DVD for 2013) contains 5484 complete reviews, 2341 protocols for reviews in production, and 22,600 short summaries of systematic reviews published in the general medical literature. In addition, there are citations of 692,000 randomized controlled trials, and 15,700 cited papers in the Cochrane methodology register. The health technology assessment database contains some 12,000 citations. Ninety-four new reviews have been published in the previous 3 months, of which four have potential relevance for practitioners in pain and palliative medicine. The impact factor of the Cochrane Library stands at 5.715. Readers are encouraged to access the full report for any articles of interest, as only a brief commentary is provided.     

LEVOMEPROMAZINE FOR NAUSEA AND VOMITING IN PALLIATIVE CARE

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD and monthly online (http://www.thecochranelibrary.com). The April 2013 issue (2nd DVD for 2013) contains 5484 complete reviews, 2341 protocols for reviews in production, and 22,600 short summaries of systematic reviews published in the general medical literature. In addition, there are citations of 692,000 randomized controlled trials, and 15,700 cited papers in the Cochrane methodology register. The health technology assessment database contains some 12,000 citations. Ninety-four new reviews have been published in the previous 3 months, of which four have potential relevance for practitioners in pain and palliative medicine. The impact factor of the Cochrane Library stands at 5.715. Readers are encouraged to access the full report for any articles of interest, as only a brief commentary is provided.     

益气活血剂对糖尿病患者的血流特点及肾小球的超滤状态的影响

目的：探讨益气活血剂对糖尿病患者血流特点及肾小球超滤状态的影响。方法：选取2005年9月—2009年6月2型糖尿病肾病（DN）患者87例,根据治疗方法不同分为两组,对照组42例予以降糖药物等基本治疗,观察组45例在对照组的基础上采用益气活血剂治疗,8周后,对比两组患者的疗效和血流特点及肾小球滤过功能。结果：观察组治疗有效率77.8%（35/45）显著高于对照组52.4%（22/42）,治疗后甲组血流特点显著优于对照组,24 h尿蛋白定量和Scr显著低于对照组,Ccr显著高于对照组,差异均具有统计学意义（均P〈0.05）。结论：益气活血剂显著改善糖尿病患者的血流特点及肾小球的超滤状态。     

Attenuation of diabetic nephropathy by Chaihuang-Yishen granule through anti-inflammatory mechanism in streptozotocin-induced rat model of diabetics

Ethnopharmacological relevance

Traditional Chinese medical herbs have been used in China for a long time to treat different diseases. Based on traditional Chinese medicine (TCM) principle, Chaihuang-Yishen granule (CHYS) was developed and has been employed clinically to treat chronic kidney disease including diabetic nephropathy (DN). The present study was designed to investigate its mechanism of action in treatment of DN.

Materials and methods

Diabetic rats were established by having a right uninephrectomy plus a single intraperitoneal injection of STZ. Rats were divided into four groups of sham, diabetes, diabetes with CHYS and diabetes with fosinopril. CHYS and fosinopril were given to rats by gavage for 20 weeks. Samples from blood, urine and kidney were collected for biochemical, histological, immunohistochemical and molecular analyses.

Results

Rats treated with CHYS showed reduced 24 h urinary protein excretion, decreased serum TC and TG levels, but CHYS treatment did not affect blood glucose level. Glomerular mesangial expansion and tubulointerstitial fibrosis in diabetic rats were significantly alleviated by CHYS treatment. Moreover, CHYS administration markedly reduced mRNA levels of NF-κB p65 and TGF-β1, as well as decreased protein levels of NF-κB p65, MCP-1, TNF-α and TGF-β1 in the kidney of diabetic rats.

Conclusions

CHYS ameliorates renal injury in diabetic rats through reduction of inflammatory cytokines and their intracellular signaling.     

短膜虫试验—HRP—SPA免疫组化法检测SLE患者抗双股DNA抗体

本文介绍几种简易的培养短膜虫的培养基,以此培养的短膜虫动基体作抗原基质,用HRP—SPA免疫组化法检测抗双股DNA抗体,取得良好效果。45例SLE病人阳性率为84.4％,其中32例活动性SLE病人阳性率达96.9％;30名正常人和19例其他结缔组织病患者均为阴性。结果表明该方法,敏感、特异而又简便。     

糖尿病肾病患者D-二聚体和脂蛋白(a)的变化及其相关性研究

目的:观察血浆D-二聚体(D-dimer,DD)和血清脂蛋白(a)[Lp(a)]在糖尿病肾病(DN)中的变化并 探讨两者之间的关系。方法:根据尿白蛋白排泄率(UAER)将126例2型糖尿病(DM)患者分为单纯糖尿病组(SDM 组)、早期糖尿病肾病组(EDN组)和临床糖尿病肾病组(CDN组),45名健康者作为对照组,分别测定各组血浆DD和 血清Lp(a)的水平。结果:DD、Lp(a)水平SDM组与对照组比较无统计学差异(P>0.05),但EDN和CDN组显著高 于SDM组和对照组(P<0.01),CDN组显著高于EDN组(P<0.01)。DD和Lp(a)分别与UAER呈显著正相关(r= 0.523,0.426,P<0.01)。结论:DN患者血浆DD和血清Lp(a)水平随着UAER的增加而升高,两者之间关系密切,可 能与DN的进展有关。     

慢性脑缺血大鼠海马中APE的表达与神经元凋亡的实验研究

目的研究慢性脑缺血大鼠海马中DNA损伤修复相关蛋白脱嘌呤／脱嘧啶核酸内切酶／氧化还原因子-1(APE／Ref-1)的活性变化与神经元的凋亡,并探讨两者之间的相关性。方法成年雄性Wistar大鼠40只,随机分为假手术组,持久性双侧颈总动脉结扎(2-VO)1周组、3周组、8周组,每组各10只,用Western blotting检测其APE蛋白表达水平的变化,并用流式细胞仪定量检测海马神经元的凋亡程度。结果 2-VO 1周组APE蛋白的表达量明显下降,与对照组相比差异有显著性(P<0．01), 随后其蛋白表达水平逐渐上升,但仍低于对照组水平(P<0．05);用流式细胞仪检测各组的凋亡率发现 2-VO 1周组、3周组凋亡率较高,与对照组相比差异有显著性(P<0．01)。结论慢性脑缺血早期DNA 修复蛋白APE活性下降,同时其神经元凋亡率较高,后期蛋白表达水平逐渐上升,神经元的凋亡程度也逐渐下降,表明DNA损伤与修复失衡所致的神经元凋亡是慢性缺血性脑损伤发病的重要机制。     

Pro‐inflammatory self‐reactive T cells are found within murine TCR‐αβ+CD4−CD8−PD‐1+ cells

TCR‐αβ⁺ double negative (DN) T cells (CD3⁺TCR‐αβ⁺CD4^?CD8^?NK1.1^?CD49b^?) represent a minor heterogeneous population in healthy humans and mice. These cells have been ascribed pro‐inflammatory and regulatory capacities and are known to expand during the course of several autoimmune diseases. Importantly, previous studies have shown that self‐reactive CD8⁺ T cells become DN after activation by self‐antigens, suggesting that self‐reactive T cells may exist within the DN T‐cell population. Here, we demonstrate that programmed cell death 1 (PD‐1) expression in unmanipulated mice identifies a subset of DN T cells with expression of activation‐associated markers and a phenotype that strongly suggests they are derived from self‐reactive CD8⁺ cells. We also found that, within DN T cells, the PD‐1⁺ subset generates the majority of pro‐inflammatory cytokines. Finally, using a TCR‐activation reporter mouse (Nur77‐GFP), we confirmed that in the steady‐state PD‐1⁺ DN T cells engage endogenous antigens in healthy mice. In conclusion, we provide evidence that indicates that the PD‐1⁺ fraction of DN T cells represents self‐reactive cells.