二甲双胍对异氟醚麻醉小鼠血糖的影响

目的 观察二甲双胍对异氟醚麻醉小鼠血糖的影响.方法 156只8周龄雄性C57BL/6小鼠分两部分进行实验.①血糖检测:这部分实验分两步进行.首先,28只小鼠按照按随机数字表法分为未禁食组(n组)和禁食12 h组(f组);各组再分为2个亚组,对照组(Cn组/Cf组),麻醉组(An组/Af组).进一步实验使用56只小鼠按随机数字表法分为n组和f组,每组28只.两组均再按随机数字表法分为4个亚组,Cn组/Cf组,An组/Af组,二甲双胍组(Mn组/Mf组)和二甲双胍麻醉组(MAn组/MAf组),每亚组均为7只.Mn组、Mf组、MAn组和MAf组于麻醉前1.5 h腹腔注射二甲双胍40 mg/kg,An组、Af组、MAn组和MAf组均行异氟醚6h麻醉.通过尾静脉取血检测围麻醉期各时间点血糖值.②荧光定量核酸扩增检测系统(quantitative polymerase chain reaction detecting system,Q-PCR)检测:共72只小鼠.各亚组分组方法同上,分别于麻醉1、4、6h取材下丘脑,每组每个时间点取3只.Q-PCR检测腺苷酸活化蛋白激酶(adenosine monophosphate activated protein kinase,AMPK)两个亚型AMPKα1、AMPKα2的mRNA表达水平.结果 血糖水平变化:与n组比较,f组小鼠血糖显著降低[(8.25±1.02) mmol/L比(6.46±0.65) mmol/L,P＜0.05].在f组和n组中,麻醉组小鼠均出现血糖水平升高;与Cn组和Cf组比较,An组和Af组分别在麻醉0.5、1、2h和1、2、3h升高(P＜0.05);分别与Cn组和Cf组比较,Mn组和Mf组血糖水平差异无统计学意义(P＞0.05);MAn组和MAf组均于麻醉2h开始出现低血糖并持续(P＜0.05),这种差异分别在麻醉结束4h和1h后消失.下丘脑AMPK mRNA表达:1h,与Cf组比较,MAf组AMPKα1和AMPKα2mRNA表达下调(P＜0.05);4h,与Cn组和Cf组比较,An组、MAn组和Af组AMPKα1表达下调(P＜0.05),AMPKα2 mRNA表达在MAf组降低(P＜0.05);6h,与Cn组和Cf组比较,AMPKα1和AMPKα2在An组和MAn组、Af组和MAf组mRNA表达都降低(P＜0.05).结论 长时程异氟醚麻醉可使小鼠血糖呈“先高后低”改变,二甲双胍预处理后麻醉小鼠可出现持续低血糖,这一过程与下丘脑AMPK转录活性无明显关联.     

T细胞死亡相关基因8的研究进展

背景 T细胞死亡相关基因8(T cell death associated gene 8,TDAG8)受体是一种质子敏感的G蛋白耦联受体(G protein coupled receptor,GPCR),在机体内广泛表达,但其生物学功能和临床相关性仍不十分清楚.随着对TDAG8的研究不断深入,尤其是TDAG8变构激动剂和变构拮抗剂的发现,为揭示TDAG8的生理功能和作用提供了重要的研究工具.目的 通过论述TDAG8可能介导的作用及其机制,为进一步研究阐述TDAG8的生物学功能及其临床相关性提供重要的理论依据.内容 系统性地综述TDAG8的生理功能及其作用机制.趋向 TDAG8可能是炎症反应的重要调节器.     

The role of procalcitonin as a marker of diabetic foot ulcer infection

Foot ulcers are frequent in diabetic patients and are responsible for 85% of amputations, especially in the presence of infection. The diagnosis of diabetic foot ulcer infection is essentially based on clinical evaluation, but laboratory parameters such as erythrocyte sedimentation rate (ESR), white blood count (WBC), C‐reactive protein (CRP) and, more recently, procalcitonin (PCT) could aid the diagnosis, especially when clinical signs are misleading. Fifteen diabetic patients with infected foot ulcers were admitted to our department and were compared with an additional group of patients with non‐infected diabetic foot ulcers (NIDFUs). Blood samples were collected from all patients in order to evaluate laboratory markers. In the current study, the diagnostic accuracy of PCT serum levels was evaluated in comparison with other inflammatory markers such as CRP, ESR and WBC as an indicator to make the distinction between infected diabetic foot ulcers (IDFUs) and NIDFUs. CRP, WBC, ESR and especially PCT measurements represent effective biomarkers in the diagnosis of foot infections in diabetic patients particularly when clinical signs are misleading.     

C1q binding is not an independent risk factor for kidney allograft loss after an acute antibody‐mediated rejection episode: a retrospective cohort study

After kidney transplantation, C4d is an incomplete marker of acute antibody‐mediated rejection (AMR) and C1q‐binding donor‐specific antibodies (DSA) have been associated with allograft survival. However, the impact on allograft survival of C1q+ DSA after clinical AMR has not been studied yet. We analysed retrospectively in clinical AMR C4d staining and C1q‐binding impact on allograft survival. We compared clinical, histological and serological features of C4d− and C4d+ AMR, C1q+ and C1q− DSA AMR and analysed C4d and C1q‐binding impact on allograft survival. Among 500 for‐cause kidney allograft biopsies, 48 fulfilled AMR criteria. C4d+ AMR [N = 18 (37.5%)] have significantly higher number class I DSA (P = 0.02), higher microvascular score (P = 0.02) and more transplant glomerulopathy (P = 0.04). C1q+ AMR [N = 20 (44%)] presented with significantly more class I and class II DSA (P = 0.005 and 0.04) and C4d+ staining (P = 0.01). Graft losses were significantly higher in the C4d+ group (P = 0.04) but similar in C1q groups. C4d+ but not C1q+ binding was an independent risk factor for graft loss [HR = 2.65; (1.11–6.34); P = 0.028]. In our cohort of clinical AMR, C4d+ staining but not C1q+ binding is an independent risk factor for graft loss. Allograft loss and patient survival were similar in C1q+ and C1q− AMR.     

In situ reprogramming to transdifferentiate fibroblasts into cardiomyocytes using adenoviral vectors: Implications for clinical myocardial regeneration

Objective

The reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells improves ventricular function in myocardial infarction models. Only integrating persistent expression vectors have thus far been used to induce reprogramming, potentially limiting its clinical applicability. We therefore tested the reprogramming potential of nonintegrating, acute expression adenoviral (Ad) vectors.

Effects of Sirt1 gene knockout on chronic kidney disease induced by 5/6 nephrectomy in mice and VEGF/Flk?1 signaling pathway

Objective To investigate the effect of Sirt1 gene knockout on chronic kidney disease induced by 5/6 nephrectomy in mice and vascular endothelial growth factor (VEGF)/fetal liver kinase-1 (Flk-1) signaling pathway. Methods Twenty four male Sirt1+/+ and Sirt1+/- mice were randomly divided into four groups: Sirt1+/+ mice with sham-operation (WT-Sham, n=6), Sirt1+/- mice with sham-operation (KO-Sham, n=6), Sirt1+/+ mice with 5/6 nephrectomy (WT-Nx, n=6) and Sirt1+/- mice with 5/6 nephrectomy (KO-Nx, n=6). Proteinuria was determined by urine collection from 8:00 to 8:00 the next day at 20 weeks. Serum creatinine (Scr), urea nitrogen (BUN) and the renal pathological changes were measured after 20 weeks. Expressions of Sirt1, collagenⅠ and transforming growth factor β (TGF-β) were used to analyze the changes of renal fibrosis by immunohistochemistry staining. Real-time PCR and Western blotting were used to measure the mRNA and protein expressions of Sirt1, fibronectin, collagenⅠ,VEGF and Flk-1 in kidney. Results Sirt1 expressed in glomerular endothelial cells, podocytes, mesangial cells and renal tubular epithelial cells in Sirt1+/+ mice, while Sirt1 expression intensity was significantly reduced in Sirt1+/- mice. Compared with the WT-Sham group, WT-Nx group had increased proteinuria, BUN, Scr, glomerular sclerosis index and tubulointerstitial fibrosis index at 12 weeks after operation (all P＜0.01), and KO-Nx group had exacerbated the above up-regulations (all P＜0.01). Compared with those in WT-Sham group, the expressions of fibronectin, collagenⅠ and TGF-β were up-regulated in WT-Nx group (all P＜0.01), and were significantly augmented in KO-Nx group (all P＜0.01). Compared with those in WT-Sham group, renal mRNA and protein expressions of VEGF and Flk-1 were decreased in WT-Nx group, and KO-Nx group aggravated their down-regulation (all P＜0.01). Conclusions Sirt1 gene knockout can increase proteinuria and Scr, and aggravate renal pathology and renal fibrosis in 5/6 nephrectomized mice, which is associated with the inhibition of VEGF/Flk-1 signaling pathway. It is suggested that Sirt1 may be a potential therapeutic target of chronic kidney disease.     

血清超敏C反应蛋白与急性脑梗死的相关性研究

目的探讨血清超敏C反应蛋白(hsCRP)水平与急性脑梗死病情严重程度及危险因素的关系。方法采用全自动生化分析仪测定186例动脉粥样硬化性血栓性脑梗死(ACI)及155例腔隙性脑梗死(LI)患者的血清hsCRP、血糖、血脂等指标,并与329名健康者进行对照。同时对急性脑梗死患者血清hsCRP水平与病情进行相关分析。结果ACI组和LI组的hsCRP水平显著高于正常对照组(均P<0.05);hsCRP水平与急性脑梗死患者神经功能缺损程度相关(P<0.05);hsCRP水平与ACI组年龄、舒张压、血糖、三酰甘油水平呈正相关(r=0.261、0.222、0.261、0.166,均P<0.05),与LI组患者的年龄、收缩压、血糖、总胆固醇水平呈正相关(r=0.294、0.456、0.245、0.402,均P<0.05),与高密度脂蛋白水平负相关(r=-0.371,P<0.05)。结论hsCRP水平与急性脑梗死的病情严重程度明显相关;并与其危险因素相关。     

DDX家族与肿瘤的相关性研究进展

DEAD-box家族是一类以D(Asp)-E(Glu)-A(Ala)-D(Asp)为保守序列的RNA解旋酶家族,参与需要RNA调节的所有细胞过程.研究表明,DDX家族很多成员在肿瘤组织中表达失调,并且参与肿瘤的发生、发展,在肿瘤细胞的增殖、凋亡、细胞周期、侵袭、转移以及代谢等方面发挥关键作用,可以作为肿瘤的诊断、恶性程度的评价、临床预后的预测等新的分子标志物,也为肿瘤的治疗提供了新的潜在分子靶标.本文就DDX家族的结构、功能、以及与肿瘤的关系作一综述.     

不同水平蛋白质饮食对大鼠Ⅱ期压疮愈合的影响

目的研究不同水平的蛋白质饮食对大鼠Ⅱ期压疮模型创面愈合的影响。方法将140只大鼠随机分为五组,采用磁铁压迫持续缺血损伤复制大鼠Ⅱ期压疮模型,造模成功后分别给予粗蛋白含量为10%、15%、20%、25%、30%的饮食干预。结果 30%蛋白组因死亡较多(12只死亡)被剔除,20%蛋白组愈合时间最短,15%蛋白组次之,10%蛋白组愈合时间最长,四组均在压疮发生后的前1周愈合最快。结论压疮发生后蛋白供给并非越多越好,应制定个体化蛋白质饮食干预计划,在压疮发生前期肉芽组织增长最快时期补充适量蛋白质对于压疮愈合效果最佳。