婴儿血管瘤发病过程中的关键信号通路

婴儿血管瘤是婴幼儿期最常见的良性肿瘤,其发病机制尚未阐明.研究证实,异常的血管发生与血管生成是导致婴儿血管瘤增殖的病理学基础.多条关键的信号通路参与婴儿血管瘤的血管发生与血管生成的调控,包括血管内皮生长因子/血管内皮生长因子受体信号通路、Notch信号通路、血管紧张素/Tie信号通路、哺乳动物西罗莫司靶蛋白信号通路、肾素-血管紧张素系统信号通路以及β受体信号通路.这些信号通路相互作用,共同促进婴儿血管瘤的异常增殖.     

他克莫司与西罗莫司根据细胞周期序贯用药对阿霉素肾病大鼠的影响

目的 观察他克莫司、西罗莫司根据细胞周期序贯联合用药对阿霉素肾病大鼠的治疗效果.方法 将24只雄性SD大鼠模型完全随即分为正常对照组、肾病组及治疗组,各8只;测定3组大鼠的尿蛋白定量、血生化指标;免疫组化、定时定量聚合酶链反应检测肾组织Nephrin、Podocin表达以及肾组织结缔组织生长因子(CTGF)的表达.结果 ①肾病组在12周末可见肾小球出现局灶节段性硬化,治疗组病理变化明显减轻.②肾病组4、8、12周末尿蛋白定量[分别为(276.41±11.12)、(355.76±14.10)、(338.92 ±15.87)mg]均明显高于对照组[分别为(12.18±1.38)、(12.98 ±2.07)、(13.56±2.70)mg,P<0.01)],治疗组大鼠尿蛋白定量在8、12周末[分别为(160.64±13.72)、(126.30±14.65)mg]均明显低于肾病组(P<0.05),但高于对照组;肾病组TP、ALB明显低于对照组(P<0.01),肾病组TG、胆固醇明显高于对照组(P<0.01),治疗组TP、ALB明显高于肾病组(P<0.05).③在12周末肾病组大鼠Nephrin、Podocin蛋白和mRNA表达明显减少(P<0.01),治疗组表达较肾病组上调(P<0.05).④在12周末肾病组CTGF蛋白表达较对照组明显增加(P<0.01),治疗组较肾病组明显减少(P<0.05).结论 他克莫司、西罗莫司根据细胞周期序贯联合用药对阿霉素肾病大鼠肾组织病理学变化均有明显改善,可有效减少阿霉素肾病大鼠的尿蛋白;升高TP和ALB,降低TG和胆固醇;并可恢复足细胞相关蛋白的表达,改善肾脏纤维化.

Abstract：

Objective To assess the therapeutic effects of the sequential thempy regimens according to the theory of cell cycle in adriamycin-induced nephrooathy(AIN)rats.Methods AIN model rats were randomly divided into three groups:control group(n=8),AIN model group(n=8)and treated group(n=8).The level of24hour urinary protein,serum total protein(TP),albumin(ALB),cholesterin(Chol),triglyeride(TG),serum urea nitrogen(BUN),serum creatinine(Scr)were measured.The expression of Nephrin and Podocin were analyzed by 11.12),(355.76±14.10)and(338.92±15.87)mg]were obviously higher than control group[respectively (12.18±1.38),(12.98±2.07)and(13.56±2.70)mg].The level of24 hour urinary protein in model group at 8th and 12 th week[respectively(160.64±13.72)and(126.30±14.65)mg]was obviously lower than model group(P<0.05).The levels of TP and ALB in treatment group were significantly higher in AIN model group,and westemblot indicated the expression of CTGF in treatment group was higher than that in AIN model group(P<0.05).Conclusions The sequential combined regimens can improve the pathological changes in Adriamycin-in-duced nephropathy rats,decrease the excretion of urinary protein,increase the levels of TP and ALB and decrease the levels of TG and Chol.It also can increase the expression of Nephrin and Podocin,and ameliorate kidney fibrosis.     

用庆大霉素抗性筛选法选育西罗莫司高产菌株

用紫外线对吸水链霉菌（Streptomyces hygroscopicus）NP03进行诱变，再采用庆大霉索抗性筛选法进行处理，剂量分别为0、0．01、0．03、0．05和0．08μg／ml，共获得113株抗性突变株，其中西罗莫司产量高于出发菌株的有51株，突变株NP03-74#的生产能力达到出发菌株的134％，且遗传特性稳定。     

UPLC(超高效液相色谱)/MS/MS联用技术测定全血中的西罗莫司

目的 建立全血中西罗莫司的UPLC（超高效液相色谱）／MS／MS测定方法,方法 全血样品中加入他克莫司（FK506）作内标，用叔丁基甲醚进行提取。以乙腈与含千分之五甲酸的水溶液为流动相（40：50），色谱柱为AcquityUPLCTMBEHC。（50mm×2．1mm，1．7μm），流速0．5ml／min。三重四极杆质谱采用正离子模式，离子采集方式为多反应监测模式（MRM），离子源温度105℃，离子源电离电压为3300V，雾化气流速500L／h。采集离子（母离子／子离子）西罗莫司为931．2／864．1，FK506为822．0／577．0。结果 西罗莫司在1～240腿／L浓度范围内呈良好的线性（n=0．9995）。日内、日间精密度均在15％以内，提取回收率大于75．0％，方法回收率为95．0％～98．5％，最低检测限为0．2μg／L。结论 本方法灵敏、准确，适合临床西罗莫司的全血分析。     

RP-HPLC法测定复合洗脱支架中西罗莫司和普罗布考的含量

目的:建立以反相高效液相色谱法测定复合洗脱支架中西罗莫司和普罗布考含量的方法。方法:色谱柱为Kromasil C18,流动相为乙腈-水(梯度洗脱),流速为1.0mL·min-1,检测波长为277nm,柱温为55℃,进样量为20μL。结果:西罗莫司和普罗布考检测浓度的线性范围均为1.0~20.0μg.mL-1(r=0.9999);平均加样回收率分别为99.47%、98.35%,日内、日间RSD均小于5%。结论:本方法简便、准确,可用于西罗莫司-普罗布考复合洗脱支架的含量测定。     

冠状动脉药物涂层支架治疗急性心肌梗死

20世纪80年代以来的研究表明，在冠状动脉粥样硬化斑块破裂的基础上血栓形成，使冠状动脉急性闭塞，是导致ST段抬高的急性心肌梗死的原因。常用的血运重建方法是溶栓治疗和直接冠脉介入术（percutaneous coroanry intervention，PCI）。溶栓治疗与安慰剂对比可明显降低病死率。直接PCI可使梗死相关血管再通率高，达到心肌梗死溶栓试验（TIMI）3级血流者明显多，再闭塞率低。缺血复发少，且出血（尤其脑出血）的危险性低。Keeley等比较了两种方法的23个随机临床对照试验。直接PCI无论是短期死亡、非致死性心肌梗死、卒中．还是联合终点，都好于溶栓治疗。2004年的美国心脏学会／美国心脏协会在治疗急性心肌梗死指南中建议的对早期急性心肌梗死患者中梗塞相关血管的早期支架植入术已成为标准的治疗方案之一。     

雷帕霉素涂层支架与裸金属支架对冠脉病变的疗效

1文献类型治疗。2证据水平1b。3文献来源Schofer J,Schlüter M,G ershlick A H,et al.For the E-SIR IU S Investigators.Sirolim us-elutingstents for treatm ent of patients with longatherosclerotic lesions in sm all coronary arteries:double-blind,random ised cont     

Effect of sirolimus on renal ischaemia/reperfusion injury in normotensive and hypertensive rats

Background. Renal ischaemia/reperfusion (I/R) injury and hypertension represent major alloantigen-independent factors contributing to the development of chronic allograft nephropathy of renal allografts. In the present study, we investigated the effect of the anti-proliferative immunosuppressant, sirolimus (SIR), in a model of accelerated renal injury in hypertensive transgenic rats (TGRs). Twenty anaesthetized uninephrectomized TGRs with renin overproduction [TGR(mREN2)27] and 20 normotensive Han SD (SD) rats as genetic controls had their renal pedicles clipped for 45 min and were subsequently treated with either SIR (0.5 mg/kg per day, orally) or placebo (n=10 in each group) for 16 weeks, after which time the kidneys were harvested for morphological and immunohistochemical analysis. High-renin hypertension aggravated the functional and structural changes induced by I/R in SD animals: both SIR-treated and untreated TGRs exhibited significantly greater proteinuria and suffered from more severe glomerulosclerosis (P<0.01) and vasculopathy (P<0.01), as well as compensatory renal hypertrophy (P<0.01) and tissue TGF-1 expression, than both normotensive SD groups (P<0.01). SIR-treated SD rats showed reduced proteinuria (P<0.01), glomerulosclerosis (P<0.01), and TGF-1 expression in the glomerular epithelium and proximal tubuli (P<0.05) compared with placebo-treated SD rats. SIR-treated TGRs had significantly lower proteinuria at week 4 after I/R (P<0.01) than placebo-treated TGRs, but there were no significant differences thereafter. Morphological patterns were similar in treated and untreated TGRs at week 16. High-renin-induced hypertension aggravated the renal injury induced by I/R. Sirolimus treatment ameliorated some late functional and morphological changes induced by I/R injury in hypertensive TGRs but, particularly, in normotensive SD rats.     

冠状动脉药物涂层支架的晚期血栓

药物涂层支架（drug—eluting stent，DES）被认为是冠心病介入治疗的又一个里程碑，它能够显著降低再狭窄率和再次血管重建率，使过去经皮冠脉腔内成形术（percutaneous transluminal coronary angioplastv．PTCA）最困扰的再狭窄问题得到很大的改善．根除再狭窄终于有了希望。自从美国食品药品监督管理局（Food and Drug Administration，FDA）批准使用两种冠状动脉药物支架（西罗莫司涂层支架，Sirolimus—eluting stents，SES，