2型糖尿病肾病与血浆 tPA、PAI-1水平及HOMA- IR的关系研究

目的：探讨2型糖尿病肾病患者蛋白尿程度与血浆中组织型纤溶酶原激活物（tPA）及其抑制物（PAI-1）水平、胰岛素抵抗指数（HOMA- IR）的关系。方法根据患者24h尿白蛋白量将91例患者分为3组,2型糖尿病尿白蛋白正常组（G1组）33例、持续微量白蛋白尿组（G2组）33例和临床蛋白尿组（G3组）25例;选择健康体检者30例作为对照组（G0组）,以ELASA法检测4组的tPA、PAI-1水平,采用HOMA模型评估HOMA- IR,并比较各组间的差异。结果与G0组相比,G1组的tPA和PAI-1水平无明显变化（P＞0.05）;G2组、G3组的tPA水平明显下降（P＜0.05或0.01）,PAI-1水平明显升高（P＜0.05或0.01）;与G0组相比, G1组的HOMA- IR无明显变化（P＞0.05）;G2组、G3组的HOMA- IR明显升高（P＜0.05或0.01）;相关危险因素分析显示血浆tPA、PAI-1水平及HOMA- IR是2型糖尿病肾病的独立危险因素。结论2型糖尿病肾病患者蛋白尿程度与tPA、PAI-1水平密切相关,血浆PAI-1和胰岛素抵抗在降低2型糖尿病纤溶活性,并在2型糖尿病肾病发生、发展中发挥了重要作用。     

NEPHRIN EXPRESSION IN THE POST-NATAL DEVELOPING KIDNEY IN NORMOTENSIVE AND HYPERTENSIVE RATS

Nephrin is a slit diaphragm protein and its expression in the developing kidney is largely unknown. In this study, we explored the expression of nephrin in the developmental kidney in spontaneously hypertensive (SHR) and in Wistar-Kyoto (WKY) rats at different time points, from day 5 after birth to adulthood. Real time RT-PCR, in situ hybridization and immunohistochemistry were used to assess and quantify gene and protein expression of nephrin in the kidney. SHR had hypertension at week 10 and albuminuria at week 20. Nephrin expression in both SHR and WKY increased from day 5 to adulthood. Furthermore, both gene and protein expression of nephrin were significantly lower in SHR after birth when compared to WKY at the same age. These findings suggest that both in normotensive and hypertensive rats, nephrin expression increased from birth to the adult age and that down-regulation of nephrin in SHR evident from the early developmental kidney to adulthood may contribute to the development of albuminuria in adult SHR.     

百令胶囊对糖尿病肾病大鼠生化指标及肾组织病理学改变的影响

目的:观察百令胶囊对糖尿病肾病大鼠血压、血糖、24 h尿蛋白定量、肾功能及大鼠肾组织病理变化的作用.方法:24只大鼠随机分为对照组、模型组、治疗组,每组各8只.复制糖尿病肾病大鼠模型成功2 d后,治疗组每日灌胃百令胶囊(2.5 g/kg),模型组及对照组每日给予等量的饮用水,测定血糖及24 h尿蛋白定量;通过全自动生化分析仪检测血肌酐(Scr)、尿素氮(BUN),并计算内生肌酐清除率(Ccr);通过光镜观察肾脏病理变化.结果:给药12周后,模型组大鼠血糖、平均动脉压、24 h尿蛋白定量、Scr、BUN及左肾/体重均明显高于对照组大鼠,而Ccr低于对照组大鼠,均P＜0.05,且肾组织出现了较明显的病理损伤;经百令胶囊治疗后,大鼠平均动脉压、24 h尿蛋白定量、Scr、BUN及左肾/体重均明显减低,均P＜0.05,血糖减低,Ccr显著增高,P＜0.05,肾组织病理损伤明显减轻.结论:百令胶囊对糖尿病肾病大鼠具有肾保护作用.     

卡维地洛对原发性高血压患者肾功能的影响

目的探讨卡维地洛对原发性高血压患者肾功能的影响。方法选择1999年2月至2003年2月在我院确诊为原发性高血压患者88例，随机分为对照组与治疗组。治疗组口服卡维地洛，同时保留其他原有抗高血压药物；对照组保留原抗高血压药物治疗，除外卡维地洛。两组患者均随访12个月，血压控制目标均为〈140／90mmHg，在入选时及入选后12个月两组均检测血肌酐（Cr）、血浆肾素活性（PRA）及24h尿微量白蛋白量（Alb）。结果入选本临床研究时，Cr、PRA及Alb在两组问的比较均无显著性差异；入选治疗12个月后，治疗组Cr、PRA、Alb水平较对照组显著降低。结论卡维地洛不仅具有降压功能，更重要的是对原发性高血压患者具有独特的保护肾功能的作用。     

ACE inhibitors and proteinuria

This review discusses the clinical consequences of uninary protein loss and the effects of inhibitors of the angiotensin converting enzyme (ACE) on this clinical finding. Proteinuria appears to be an important risk factor for renal function deterioration and for cardiovascular mortality. ACE inhibitors have been shown to reduce proteinuria more effectively than other antihypertensives. Their antiproteinuric effect seems to be independent of the underlying renal disease, and is mediated by a specific, not yet fully elucidated mechanism. Urinary protein loss related phenomena, such as hypoalbuminemia and aberrant lipoprotein profile, tend to improve also during ACE inhibitor treatment. Furthermore, ACE inhibition has been shown to prevent the renal function deterioration that is frequently observed in patients with renal disease. Interestingly, it has recently been shown that in proteinuric patients with renal disease the initial proteinuria lowering response to ACE inhibition predicts long-term renal function outcome during this treatment: the more proteinuria is lowered during the first months, the better renal function will be preserved over the following years. Because of these favorable effects ACE inhibitors have become a widely used class of agents in nephrology. They are not only prescribed for lowering blood pressure in the hypertensive renal patient, but also as symptomatic treatment of patients with proteinuria, and to prevent renal function loss in patients with both diabetic and non-diabetic renal disease.R.T. Gansevoort, D. de Zeeuw, P.E. de Jong, Ace inhibitors and proteinuria. Pharm World Sci 1996; 18(6): 204–210.     

Renoprotective effects of tea catechin in streptozotocin- induced diabetic rats

Tea catechins, a class of flavonoids, are suggested to have biological effects, possibly mediated through their antioxidative properties. Recent data indicated that tea catechins suppressed proliferative changes in glomeruli and inhibited the development of glomerulosclerosis in partially nephrectomized rats. We thus sought to determine whether tea catechins may protect against renal dysfunction in streptozotocin-induced diabetic rats. Four groups of male Sprague-Dawley rats (n=11–15 per group), with and without streptozotocin-induced diabetes, were treated with and without catechins (5 mg/day) administered in the drinking water for 12 weeks. At the end of the treatment period, 24-hour urinary albumin excretion rate (AER), serum lipid peroxides as thiobarbituric acid reactive substrates (TBARS) and blood pressure were measured. Renal glomerular volume and interstitial fibrosis were assessed morphologically. Albuminuria developed progressively in untreated diabetic rats, resulting in a mean AER of 559±124 (mean±SE) versus 63±7 μg/day/100 g body weight in non-diabetic rats at 12 weeks (P<0.001). Catechin treatment significantly reduced AER to 287±56 μg/day/100 g body weight in diabetic rats (P=0.017 versus untreated diabetic rats). Increased interstitial fibrosis in the kidney, observed in untreated diabetic rats, was completely normalized with catechin treatment. Serum levels of TBARS and blood pressure were comparable among the four groups. In conclusion, administration of tea catechin retards the progression of functional and morphological changes in the kidney of streptozotocin-induced diabetic rats.     

链脲佐菌素诱导的糖尿病大鼠尿podocalyxin排泄的动态变化

目的观察链脲佐菌素(STZ)诱导的糖尿病大鼠足细胞标志蛋白podocalyxin随尿排泄的动态变化并探讨其意义。方法 STZ 65 mg/kg腹腔注射后建立糖尿病大鼠模型,正常大鼠注射等量枸橼酸缓冲液作为对照组(NC组)。分别于0周、2周、4周和8周监测两组大鼠血糖、尿白蛋白(UALB)及尿沉渣中PCX含量(UPCX)和8周末HbA1c,为消除尿量影响分别用尿肌酐(UCr)校正称为UACR(UALB/UCr)及UPCR(UPCX/UCr)。结果 (1)与健康对照组比较,糖尿病大鼠各时间点血糖和8周时HbA1c显著增高,P<0.01;(2)与健康对照组比较,2周时糖尿病大鼠UACR及UPCR即显著增高,并随时间不断增长;(3)糖尿病大鼠UPCR与UACR呈正相关(r=0.86,P<0.01)。结论足细胞损伤参与糖尿病肾脏病变的发生,尿PCX检测可作为反映糖尿病早期肾损害的指标之一。     

High risks of all-cause and cardiovascular deaths in apparently healthy middle-aged people with preserved glomerular filtration rate and albuminuria: A prospective cohort study

Background

The reason why coexistence of preserved estimated glomerular filtration rate (eGFR) and albuminuria contributes to a high risk of death and which cause of death increases all-cause mortality have not been elucidated.

Methods

A total of 16,759 participants aged 40 to 69 years with normal or mildly reduced eGFR (45–119 ml/min/1.73 m²) were enrolled and divided into six groups (group 1, eGFR: 90–119 without albuminuria; group 2, eGFR: 90–119 with albuminuria; group 3, eGFR: 60–89 without albuminuria (reference); group 4, eGFR: 60–89 with albuminuria; group 5, eGFR: 45–59 without albuminuria; group 6, eGFR: 45–59 with albuminuria) based on GFR estimated by using the CKD-EPI study equation modified by a Japanese coefficient and albuminuria (urine albumin–creatinine ratio ≥ 30 mg/g). Outcomes included all-cause death (ACD), cardiovascular death (CVD) and neoplasm-related death (NPD). Multivariable-adjusted mortality rate ratios (RR) and their 95% confidence intervals (CIs) in the groups were estimated by Poisson's regression analysis.

Results

The highest risk of ACD (RR (95% CIs): 3.95 (2.08–7.52)), CVD (7.15 (2.25–22.7)) and NPB (3.25 (1.26–8.38)) was observed in group 2. Subjects in group 2 were relatively young and had the highest levels of body mass index, blood pressure and HbA_1c and the highest prevalence of diabetes and metabolic syndrome.

Conclusion

Coexistence of preserved eGFR and albuminuria increases risks for ACD, CVD and NPD. Relatively young metabolic persons having both preserved eGFR and albuminuria should be considered as a very high-risk population.