滋阴活血汤治疗早期糖尿病肾病临床研究

目的:观察滋阴活血汤治疗早期糖尿病肾病的临床疗效。方法:选取130例早期糖尿病肾病患者,随机分为对照组和观察组,各65例。对照组给予降糖等西医对症治疗,观察组在对照组基础上给予滋阴活血汤,两组疗程均为4周。观察两组治疗前后血液流变学变化,采用全自动生化分析仪进行检测;核因子(nuclear factor,NF)-κB变化,采用双抗体夹心酶联免疫吸附试验测定;24小时尿蛋白变化,采用放射免疫法测定;两组治疗前后症状总积分变化。结果:治疗后,观察组治疗后全血黏度、红细胞压积比、纤维蛋白原水平均明显低于对照组(P0.05);观察组治疗后NF-κB及24小时尿蛋白水平均低于对照组(P0.05);观察组治疗后症状总积分明显低于对照组(P0.01);对照组有效率为81.5%,观察组为93.8%,组间比较,差异有统计学意义(χ~2=4.561,P0.05)。两组治疗中未见严重不良反应。结论:滋阴活血汤治疗早期糖尿病肾病疗效确切,安全;能有效改善患者血液流变学,降低NF-κB及24小时尿蛋白水平。     

Relationship between diabetic retinopathy and diabetic nephropathy; A longitudinal follow-up study from a tertiary care unit of Karachi,Pakistan

ObjectiveTo determine the development and progression of diabetic retinopathy in subjects with diabetic nephropathy.MethodologyThis retrospective longitudinal follow up study was conducted in outpatient department of Baqai Institute of Diabetology and Endocrinology (BIDE), a tertiary care diabetes unit of Karachi Pakistan, from January 2005 to December 2016. Type 2 diabetic subjects with newly diagnosed diabetic nephropathy (DN) and sex-age matched controls were identified from the electronic database of the institute, Health Management System (HMS). Subjects with type 1 diabetes, gestational diabetes and subjects with diabetic retinopathy (DR) at the baseline of both DN and non-DN group were excluded from the study. Statistical analyses were conducted by using SPSS version 20.ResultOut of 3056 type 2 diabetic subjects, 2389 were with DN and 667 were without DN. The incidence of retinopathy was found to be 21.7 per 1000 person years. The incidence rate ratio (IRR) of 2.57 (1.92–3.43) showed that retinopathy was significantly higher in subjects with DN as compared to subjects without DN. Kaplan-Meier survival plot confirmed that subjects with DN had a worse diabetic retinopathy-free survival than subjects without DN.ConclusionDiabetic nephropathy is an independent risk factor for the development and progression of diabetic retinopathy.     

中成药联合普利或沙坦类药物治疗糖尿病肾病的网状Meta分析＊

目的 运用网状Meta分析方法，以单纯ACEI/ARB（angiotensin receptor blockers，ARB；angiotensin-converting enzyme inhibitor，ACE）治疗为共同参照，对比海昆肾喜胶囊、黄葵胶囊、尿毒清颗粒、肾衰宁胶囊、雷公藤多苷片、金水宝胶囊、百令胶囊、火把花根片对糖尿病肾病的临床疗效。方法 计算机检索有关海昆肾喜胶囊、黄葵胶囊，尿毒清颗粒、肾衰宁胶囊、雷公藤多苷片、金水宝胶囊、百令胶囊、火把花根片联合ACEI/ARB治疗糖尿病肾病的随机对照试验。由2名研究人员独立筛选，包括质量、评估，数据采用R、Gemtc、ＲevMan 5.3软件进行网状Meta分析和传统Meta分析。最终纳入86篇RCTs，共7413例患者，涉及9种干预措施。结果 Meta分析结果显示：①在综合疗效方面，金水宝胶囊、雷公藤多苷片、肾衰宁胶囊联合ACEI/ARB排序靠前，其中雷公藤多苷片联合ACEI/ARB降低24 h尿蛋白（24 h UPQ）和尿微量蛋白（UAER）的疗效最佳，肾衰宁胶囊联合ACEI/ARB降低血肌酐（Scr）、糖化血红蛋白（HBA1C）和空腹血糖（FPG）的疗效最佳；②在安全性方面，联合中成药均较单纯ACEI/ARB治疗有一定改善，因临床异质性较大无法定量合并，所有纳入研究未发生严重不良反应。由于纳入文献质量相对偏低，得出的结论尚有待临床验证。结论 结合网状Meta分析结果和文献信息，在治疗有效率方面，金水宝胶囊联合ACEI/ARB疗效最优；在降低24 h尿蛋白（24 hUPQ）和尿微量蛋白（UAER）方面，均为雷公藤多苷片联合ACEI/ARB疗效最优；在降低血肌酐（Scr）、糖化血红蛋白（HBA1C）和空腹血糖（FPG）方面，均为肾衰宁胶囊联合ACEI/ARB疗效最优。     

黄芪和山药配伍微粉对糖尿病肾病大鼠抗氧化能力的影响

目的:观察黄芪和山药配伍微粉对糖尿病肾病大鼠抗氧化能力的影响,探讨其保护大鼠肾功能的作用机制。方法:采用单侧肾脏切除合并腹腔注射链脲佐菌素的方法诱导建立糖尿病肾病大鼠模型,将造模成功的45只大鼠随机分为模型对照组12只、卡托普利组11只、微粉低剂量组11只和微粉高剂量组11只,另取10只作为假手术对照组。卡托普利组灌胃卡托普利溶液剂量为13.5 mg·kg-1,微粉低剂量组灌胃微粉溶液,剂量为5.4 g·kg-1,微粉高剂量组灌胃微粉溶液,剂量为10.8 g·kg-1,假手术对照组和模型对照组大鼠灌胃等容积蒸馏水,每日1次,连续给药6周。给药结束后,采用免疫浊度法于计算24 h尿微量白蛋白量,运用全自动生化仪测定血清血尿素氮(Blood urea nitrogen,BUN)、血肌酐(Serum creatinine,Scr)含量,采用黄嘌呤氧化酶法测定血清超氧化物歧化酶(Superoxide Dismutase,SOD)活性,硫代巴比妥酸法测定血清丙二醛(malonaldehyde,MDA)含量。结果:微粉高剂量组能明显改善糖尿病肾病大鼠的一般状况,体质量较模型对照组明显增加,肾脏肥大指数明显减小,差异具有统计学意义(P0.05)。与假手术组比较,模型对照组大鼠24 h尿蛋白定量、血清BUN、血清Scr均明显升高,微粉高剂量组和卡托普利组较模型对照组降低,差异具有统计学意义(P0.05)。与假手术组比较,模型对照组血清SOD活性明显降低,血清MDA含量明显升高,微粉高剂量组和卡托普利组与模型对照组比较,血清SOD活性升高,血清MDA含量降低,差异具有统计学意义(P0.05)。结论:黄芪和山药配伍微粉可明显降低糖尿病肾病大鼠尿蛋白的排泄,降低血清BUN和Scr水平,升高血清SOD活性,降低MDA含量,具有明显的肾脏保护作用,黄芪和山药微粉对糖尿病肾病大鼠肾脏的保护作用与提高抗氧化能力有关。     

应用全基因组拷贝数变异方法探索参芪膜肾方治疗特发膜性肾病基因水平机制的研究

目的：探索特发膜性肾病患者全基因组拷贝数变异与参芪膜肾方疗效的关系。方法：选取80例经参芪膜肾方或经典的激素联合环磷酰胺方案治疗后完全缓解和无效的IMN病例,分为中药有效组（36例）、中药无效组（11例）、西药有效组（18例）和西药无效组（15例）。提取外周血基因组DNA并应用Affymetrix Genome-Wide Human SNP Array 6.0芯片检测全基因组基因拷贝数,应用CNVhac软件进行拷贝数变异（ CNV）分析。结果：中药有效组与中药无效组在第5、第6及第8染色体上检测到的CNVs差异具有统计学意义（P＜0.05）。其中位于6号染色体上的HLA族基因在中药有效组多数病例中表现为拷贝数扩增,而中药无效组的多数病例则表现为拷贝数缺失。西药有效组与西药无效组之间未检测到具有统计学差异的CNVs。结论：基因背景差异可能是导致参芪膜肾方取得不同疗效的基因水平机制,HLA的同族基因拷贝数变异影响参芪膜肾方疗效的发挥,前者有望成为该方治疗IMN的疗效预测因子,值得进一步深入研究。     

Expression of NLRP3 inflammasome in the BSA-overloaded rats kidney

Objective To observe NLRP3 inflammasome expression and inflammatory cells infiltration in the BSA-overloaded rats kidney, and to investigate the potential mechanism of renal injury induced by proteinuria. Methods After unilateral right nephrectomy, eighteen healthy male Wistar rats were randomly divided into two groups: protein overload nephropathy model group (n=10), treated with intraperitoneal injections of bovine serum albumin (BSA); control group (n=8), treated with intraperitoneal injections of 0.9% saline for 9 weeks. Body weigh were measured every week and 24 h urine were collected in 0, 2, 5, 7, 9 week. The plasma levels of blood total protein (TP), albumin (Alb), serum creatinine (Scr) and blood urea nitrogen (BUN) were determined by automatic analyzers. Renal pathological changes were evaluated by PAS and Masson stains. Immunohistochemical staining was used to detect the expression of NLRP3, caspase-1, IL-1β, and IL-18, as well as the types of inflammatory cells. The NLRP3, caspase-1, IL-1β, and IL-18 protein and mRNA levels were also analyzed by Western blot and real-time PCR in two groups. Results It was found that there was a significant increase of proteinuria and BUN in model group compare to that in control group (all P＜0.05). However, there were no significant changes in body weight, TP, Alb and Scr between the two groups. Morphological study demonstrated that renal tubular epithelial cell injury, proteinaceous casts in tubular lumen, accompanying with the dominant macrophages and lymphocytes infiltration in interstitium in model group. The immunohistochemistry showed that there were more T (CD3+), B cells (CD20+) and macrophages (CD68+) in renal interstitium in model group than that in control group (P＜0.05). Tubulointerstitial injury score was higher than that of the control group (P＜0.05). Immunohistochemistry, Western blot and real-time PCR all showed that the expression of NLRP3, caspase-1, IL-18 and IL-1 β were significantly increased compared to those in control group (P＜0.05). Furthermore, there were significant correlations between proteinuria and IL-1β/IL-18 expression (P＜0.05). Conclusion NLRP3 inflammasome activation is involved in tubulointerstitial inflammation caused by proteinuria.     

高糖、胰岛素影响肾小球系膜细胞葡萄糖转运蛋白4 mRNA表达的研究

目的:探讨高糖、胰岛素对肾小球系膜细胞葡萄糖转运蛋白4 mRNA表达的影响,进一步研究GluT4在糖尿病肾病发病中的作用。方法:将培养的鼠1097系膜细胞分为8组:正常对照组,生理浓度胰岛素组(10-9M),低浓度胰岛素组(10-8M),高浓度胰岛素组(10-6M),高糖组(30mM),甘露醇组,高糖加高浓度胰岛素组,高糖加生理浓度胰岛素组。采用RT-PCR法检测GluT4 mRNA含量。结果:①正常系膜细胞可检测到GluT4mRNA。②高糖组GluT4 mRNA表达为对照组的58.7%(p<0.05);10-8M胰岛素组、10-6M胰岛素组分别为对照组的230.2%和297.2%(P<0.01);高糖加10-6M胰岛素组,高糖加10-9M胰岛素组分别为高糖组的170.6%和140.3%(p<0.05)。结论:①正常系膜细胞有GluT4 mRNA表达。②高糖可抑制GluT4 mRNA表达,胰岛素有一定拮抗作用,且呈剂量依赖性。③GluT4是糖尿病肾病发生发展中的重要因子。