唐红运用中药内外合治糖尿病周围神经病变经验

介绍唐红主任医师治疗糖尿病周围神经病变的临床经验,主张运用中药内外合治,并自创活血化瘀之糖络宁外敷穴位。     

Genetic susceptibility to type 2 diabetic nephropathy in human and animal models

SUMMARY:   Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in Japan, Western Europe, and the United States. Mega studies such as Diabetes Control and Complication Trial (DCCT), Epidemiology of Diabetes Interventions and Complications (EDIC), and the United Kingdom Prospective Diabetes Study (UKPDS) clarified that poor glycemic and blood pressure control are undoubtedly involved in the development of nephropathy. However, these factors are not sufficient to predict which diabetic patients will develop renal disease, because not all patients with poor glycemic and blood pressure control develop renal disease. Since ethnic variations and familial clustering of diabetic nephropathy have been observed, genetic factors might contribute to susceptibility to this disease. Several methods such as (genome wide) association studies, sib-pair analysis, and quantitative trait loci (QTLs) analysis are available to examine polygenic diseases. However, no mutations that could explain the majority of nephropathy cases have been identified so far. The development of most diabetic nephropathy might be explained by the polygenic effect (i.e. many minor gene-gene interactions might be very important in the development of nephropathy). Identification of candidate genes of nephropathy enables targeting of therapy in patients at risk and development of novel therapeutic agents.     

Antibody Response Against the Glomerular Basement Membrane Protein Agrin in Patients with Transplant Glomerulopathy

Chronic allograft nephropathy (CAN) of renal allografts is still the most important cause of graft loss. A subset of these patients have transplant glomerulopathy (TGP), characterized by glomerular basement membrane (GBM) duplications, but of unknown etiology. Recently, a role for the immune system in the pathogenesis of TGP has been suggested. In 11 of 16 patients with TGP and in 3 of 16 controls with CAN in the absence of TGP we demonstrate circulating antibodies reactive with GBM isolates. The presence of anti-GBM antibodies was associated with the number of rejection episodes prior to diagnosis of TGP. Sera from the TGP patients also reacted with highly purified GBM heparan sulphate proteoglycans (HSPG). Indirect immunofluorescence with patient IgG showed a GBM-like staining pattern and colocalization with the HSPGs perlecan and especially agrin. Using patient IgG, we affinity purified the antigen and identified it as agrin. Reactivity with agrin was found in 7 of 16 (44%) of patients with TGP and in 7 of 11 (64%) patients with anti-GBM reactivity. In conclusion, we have identified a humoral response against the GBM-HSPG agrin in patients with TGP, which may play a role in the pathogenesis of TGP.     

Workshop on Late Renal Allograft Dysfunction

Despite continued improvement in incidence of acute immune injury and short-term graft survival, late allograft dysfunction remains a significant problem in the renal transplant population. Recent reports suggest that rates of renal function decline are quite varied in the overall recipient population, and that individual rates for many recipients may not change substantially over time. Moreover, analyses also reveal distinct predictive factors for both early and late functional decline. Long-term outcome studies for renal transplantation, however, might be significantly limited by incomplete data sets for assessing clinical endpoints. In view of the heterogeneous factors that may cause progressive allograft injury, more routine biopsy sampling would allow a more complete characterization of induced injuries. Elucidating mechanisms of renal fibrosis in response to injury, in experimental systems and humans, is also an important goal in better understanding chronic allograft damage. Regulation of cell senescence genes and epithelial to mesenchymal transition, studied in other models of renal fibrosis, are likely relevant to studies of renal allograft dysfunction. Recent technical advances in analyzing biological samples may play a pivotal role in identifying and validating surrogate markers of allograft function for future interventional trials in transplantation.     

Mycophenolate Mofetil Is Associated with Altered Expression of Chronic Renal Transplant Histology

Mycophenolate mofetil (MMF) reduces acute rejection in controlled trials of kidney transplantation and is associated with better registry graft survival. Recent experimental studies have demonstrated additional antifibrotic properties of MMF, however, human histological data are lacking. We evaluated sequential prospective protocol kidney biopsies from two historical cohorts treated with cyclosporine (CSA)-based triple therapy including prednisolone and either MMF (n = 25) or azathioprine (AZA, n = 25). Biopsies (n = 360) were taken from euglycemic kidney-pancreas transplant recipients. Histology was independently assessed by the Banff schema and electron microscopic morphometry. MMF reduced acute rejection and OKT3 use (p < 0.05) compared with AZA. MMF therapy was associated with limited chronic interstitial fibrosis, striped fibrosis and periglomerular fibrosis (p < 0.05-0.001), mesangial matrix accumulation (p < 0.01), chronic glomerulopathy scores (p < 0.05) and glomerulosclerosis (p < 0.05). MMF was associated with delayed expression of CSA nephrotoxicity, reduced arteriolar hyalinosis, striped fibrosis and tubular microcalcification (p < 0.05-0.001). The beneficial effects of MMF remained in recipients without acute rejection. Retrospective analysis shows that MMF therapy was associated with substantially reduced fibrosis in the glomerular, microvascular and interstitial compartments, and a delayed expression of CSA nephrotoxicity. These outcomes may be due to a limitation of immune-mediated injury and suggest a direct effect of reduced fibrogenesis.     

氯沙坦对糖尿病大鼠肾组织TLR4表达的影响

目的观察氯沙坦对糖尿病大鼠肾组织TOLL样受体4（TLR4）表达的影响。方法采用链脲佐菌素（STZ，65mg·kg^-1）腹腔注射建立糖尿病大鼠模型，将其分为对照组、模型组、治疗组。治疗组在造模成功后1周给予氯沙坦20mg·kg^-1灌胃。12周后测3组24h尿蛋白、血肌酐、肾重／体重、血CRP及TNF-α水平；观察肾脏病理形态学变化；应用免疫组化法检测肾组织TLR4、核因子-κB（NF-κB）的蛋白表达。结果模型组24h尿蛋白、血肌酐、尿素氮、肾重／体重明显升高，肾小球肥大、细胞增生，PAS阳性物质沉积增多。血CRP、TNF-α含量及肾组织TLR4、NF-κB的蛋白表达上调。经氯沙坦治疗后，血CRP、TNF-α含量下降，TLR4、NF-κB的表达下调。结论氯沙坦对糖尿病肾病具有保护作用，其作用机制可能是通过下调NF-κB、TLR4的表达，降低血浆CRP、TNF-α含量来实现的。     

冠状动脉介入诊疗中非离子型对比剂对肾功能的影响和氯沙坦的保护价值

目的评价采用非离子低分子对比剂行冠脉造影和介入治疗对于肾功能的影响,并比较单纯冠脉造影和冠脉介入治疗手术前后肾功能的差异;评价氯沙坦对于冠脉介入治疗前后肾功能(血肌酐)和尿微量白蛋白的影响。方法根据冠状动脉造影的结果将我院收治的171例患者分3组,第1组为造影阴性组(CAG,73例),第2组为常规介入治疗组(PCI,52例),第3组为介入治疗 氯沙坦组(46例);研究对比剂对3组肾脏功能和尿微量白蛋白的影响。在检查前及术后的第1、3、7天分别测试尿微量白蛋白和肾功能(血肌酐),然后比较对比剂碘佛醇应用前后各组的差异。结果各组血肌酐均无明显变化,而PCI组尿微量白蛋白比CAG组的患者高(P<0.05);在氯沙坦干预后,PCI后尿微量白蛋白有明显下降(P<0.05)。结论CAG和PCI时,非离子低分子对比剂对肾功能(血肌酐)无明显影响,而尿微量白蛋白在术后有不同程度的升高,在PCI组中更明显;氯沙坦能降低PCI术后的尿微量白蛋白,可能具有预防对比剂肾病的作用。     

低铁与低热量饮食延缓糖尿病肾病的进展

目的探讨低铁与低热量饮食是否能延缓糖尿病肾病的进展。方法以168例Ⅱ型糖尿病肾病患者为研究对象,随机分为两组,对照组予以常规治疗,治疗组在进行同样常规治疗的同时,予低铁、低热量饮食。结果平均随访37±22个月,治疗组患者血清铁水平显著降低,与对照组比较,有显著差异(P<0.01);治疗组血清肌酐189±78μmmol/L,对照组257±115μmmol/L,两组比较,有显著差异(P<0.01)。治疗组有6例患者达到终止随访目标,血红蛋白低于80g/L和或红细胞压积<33%,需进行促红素治疗,占17.6%;对照组有10例达到终止目标,占35.7%,两组比较,有显著差异(P<0.01)。结论低铁饮食治疗能显著降低糖尿病肾病患者铁负荷,配合低热量饮食治疗,能明显延缓糖尿病肾病的进展。     

刺五加注射液及抗凝剂对糖尿病足的早期干预治疗

目的观察刺五加注射液及抗凝剂(潘生丁、肠溶阿斯匹林)对糖尿病足早期干预治疗的影响。方法将符合1999年WHO诊断标准的100例糖尿病合并早期足病变的患者分为两组:干预治疗组50例,对照组50例。在控制血糖、血压、糖尿病教育的基础上,干预组予以静滴刺五加注射液及口服抗凝剂(潘生丁、肠溶阿斯匹林)治疗,对照组为口服VitB1、VitB6、复方丹参片治疗。观察治疗前后两组患者足背动脉搏动、皮肤颜色、温度,痛、温、触觉等相关指征,血糖、HbA1c、血TG、TC、HDL-C,及血流变学、眼底病变、心脑血管事件发生率等。结果干预组糖尿病足病变治疗好转率高,恶化发展率低,心脑血管事件发生率少。血脂、血流变学、下肢血管多普勒彩超及眼底病变等好转改善明显,与对照组比较差异有统计学意义(P<0.05或P<0.01)。结论刺五加注射液及抗凝剂(潘生丁、肠溶阿斯匹林)对糖尿病足病变的早期干预治疗疗效显著,有重要的临床意义。