链霉素诱导的2型糖尿病大鼠模型的肾脏功能变化

目的通过观察链霉素诱导的2型糖尿病大鼠模型肾脏功能的变化,以探讨此种模型是否适用于糖尿病肾损害的研究。方法采用链脲佐菌素(streptozotocin,STZ)辅以高脂饮食建立2型糖尿病大鼠模型,筛选造模成功的大鼠为糖尿病组,并与正常大鼠比较,造模后8周观察两组大鼠血糖、血尿素氮(blood urea nitrogen,BUN)、血肌酐(creatinine,CR)、血糖基化终末产物(Advanced glycation end products,AGE)、尿微量白蛋白、肾重指数的变化以及AGE受体(Receptor of AGE,RAGE)、蛋白激酶C(protein kinase C,PKC)、蛋白激酶A(protein kinase A,PKA)在肾脏的表达变化。结果糖尿病组的血糖、血尿素氮、血肌酐、血AGE、尿微量白蛋白以及肾重指数均明显高于正常组(P0.05),RAGE、PKC的mRNA以及蛋白表达水平均较正常组高(P0.05),PKA的mRNA和蛋白表达水平则较正常组低(P0.05)。结论 STZ诱导的2型糖尿病大鼠模型在造模后第8周肾脏功能存在明显的损害,并且导致肾脏损害的上游重要介质RAGE、PKC、PKA在第8周都有着明显的变化。此种模型能够用于糖尿病肾损害的研究,并且是观察中早期糖尿病肾病的较好的模型。     

解聚复肾宁对糖尿病肾病大鼠TNF—OL、MCP-1的影响

目的观察解聚复肾宁（Jiejufushenning,JJFSN）对糖尿病（Diabetes mellitus,DM）大鼠肾组织肿瘤坏死因子-α（Tumorneerosisfactor-alpha,TNF-α）、单核细胞趋化蛋白-1（Monocyte chemoattractant protein-1,MCP-1）和血清TNF-α的影响,探讨其肾保护作用机制。方法腹腔注射链脲佐菌素（Streptozotocin,STZ）建立SD大鼠DM模型,将成模DM大鼠随机分为3组：DM模型组（B组）、JJFSN组（C组）、厄贝沙坦（Irbesartan）组（D组）,另设正常对照组（A组）。采用相应干预措施处理12周。常规方法测定12周末各组大鼠空腹血糖（FBG）、血尿素氮（BUN）、血肌酐（Scr）、肾重／体重（KW／BW）、24h尿蛋白（24huFro）;放免法测血清TNF-α含量：免疫组织化学方法测肾组织TNF—Ot、MCP-1的表达;PAS染色评估细胞外基质;电镜观察肾组织超微结构改变。结果与A组相比．B组大鼠FBG、BUN、Scr、KW／BW、24huPro及血清TNF-α升高（P〈0．05）,肾组织TNF—Ot、MCP-1表达明显增高（P〈0．05）;肾组织超微结构明显异常;C组和D组上述指标显著改善（P〈0．05）,肾组织超微结构异常改善。结论竹FSN能延缓DM大鼠肾损害进程,其机制可能与抑制TNF-α、MCP-1上调有关。     

脂联素对1型糖尿病小鼠视网膜节细胞和血管的影响

目的:研究脂联素对1型糖尿病小鼠视网膜节细胞和血管的影响.方法:使用玻璃体腔内注射脂联素,腹腔内注射链脲佐菌素(STZ),免疫荧光,非侵入性眼压测量等实验方法,对1型糖尿病的视网膜节细胞数量的改变和血管形态的变化做研究.结果:1型糖尿病鼠脂联素组的眼压比1型糖尿病鼠对照组明显低(p＜0.01),而与正常鼠脂联素组相比明显升高(p＜0.01).与1型糖尿病鼠对照组相比,1型糖尿病鼠脂联素组的视网膜血管管径更粗一点.Brn3a+视网膜神经节细胞在1型糖尿病鼠脂联素组明显比1型糖尿病鼠对照组要多(p＜0.05),而与正常鼠脂联素组比较明显低一些(p＜0.01).结论:脂联素可明显改善1型糖尿病小鼠视网膜神经节细胞数量的下降,并可延缓视网膜血管形态的变化.APN有成为一种治疗糖尿病性视网膜病变的潜在可能性.     

Pituitary response to gonadotropin-releasing hormone in diabetic male rats

Summary The rise in serum luteinizing hormone concentration after treatment with gonadotropin-releasing hormone was less in diabetic castrated male rats than control castrates. In intact male rats, gonadotropin-releasing hormone treatment resulted in higher serum luteinizing hormone concentrations in diabetic than in control rats.Acknowledgments. This work was supported in part by a grant from the Medical Research Council of Canada. The authors are grateful to Dr G.D. Niswender, Dr L.E. Reichert, Jr. and the National Institute of Arthritis, Metabolism and Digestive Diseases, Rat Pituitary Hormone Program for providing radioimmunoassay materials. The streptozotocin was kindly provided by Dr W.E. Dulin, The Upjohn Company. D.B. Beaton and J. Brunka provided excellent technical assistance.     

Glomerular filtration rate and kidney blood flow in alloxan and streptozotocin diabetic rats.

Glomerular filtration rate (GFR), cardiac output, regional blood flow and kidney weight were measured in alloxan and streptozotocin diabetic rats at different times after the administration of diabetogen. A high GFR was found together with increased kidney weight and reduced blood flow.     

Structural relationships between the endogenous volatile urinary metabolites of experimentally diabetic rats and certain neurotoxins

Summary High resolution glass capillary gas chromatography and GC/MS were utilized to examine qualitative and quantitative variations from normal of urinary volatile metabolites of long-term alloxan and streptozotocin diabetic rats. Volatile metabolites were structurally compared with known neurotoxins to examine any possible relationship between these metabolites and the development of the diabetic polyneuropathy.Acknowledgment. This research was supported by grant No. 24349 from the National Institute of General Medical Sciences, U.S. Public Health Service.     

Glomerular filtration rate and kidney blood flow in alloxan and streptozotocin diabetic rats

Summary Glomerular filtration rate (GFR), cardiac output, regional blood flow and kidney weight were measured in alloxan and streptozotocin diabetic rats at different times after the administration of diabetogen. A high GFR was found together with increased kidney weight and reduced blood flow.     

Distal axonopathy in streptozotocin diabetes in rats

Summary We noted the earliest morphological changes in the motor endplates 8 weeks after the induction of streptozotocin diabetes in rats. Morphometric measurements showed reduced axonal areas of the lateral plantar and the sicatic nerves in the diabetic rats 28 but not 2 and 8 weeks after the experiment. These findings suggested distal axonopathy.     

Distal axonopathy in streptozotocin diabetes in rats

We noted the earliest morphological changes in the motor endplates 8 weeks after the induction of streptozotocin diabetes in rats. Morphometric measurements showed reduced axonal areas of the lateral plantar and the sciatic nerves in the diabetic rats 28 but not 2 and 8 weeks after the experiment. These findings suggested distal axonopathy.     

C-peptide fragments stimulate glucose utilization in diabetic rats

Studies of C-peptide cellular effects show that not only the full-length native peptide but also specific C-terminal fragments are biologically active in in vitro systems. In the present study, the effect of five C-peptide fragments and the native peptide on whole-body glucose turnover was studied in streptozotocin diabetic rats using the insulin clamp technique. Insulin was infused intravenously at 18 pmol kg^–1 min^–1 for 90 min and blood glucose concentration was clamped at 8 and 4 mM in diabetic and non-diabetic animals. A steady state was reached during the last 30 min of the study period. Rat C-peptide II and fragments comprising residues 27–31 and 28–31 were effective in augmenting glucose turnover in diabetic rats (+100% to 150%), while no significant effects were seen for segments 1–26, 11–19 and 11–15. The metabolic clearance rate for glucose during infusion of C-peptide or fragments 27–31 and 28–31 in diabetic rats was similar to that seen in non-diabetic animals. We conclude that C-terminal tetra- and pentapeptides, but not fragments from the middle segment of C-peptide, are as effective as the full-length peptide in stimulating whole-body glucose turnover in diabetic rats.Received 18 December 2003; received after revision 19 January 2004; accepted 21 January 2004     

Autophagy in diabetic kidney disease: regulation,pathological role and therapeutic potential

Diabetic kidney disease, a leading cause of end-stage renal disease, has become a serious public health problem worldwide and lacks effective therapies. Autophagy is a highly conserved lysosomal degradation pathway that removes protein aggregates and damaged organelles to maintain cellular homeostasis. As important stress-responsive machinery, autophagy is involved in the pathogenesis of various diseases. Emerging evidence has suggested that dysregulated autophagy may contribute to both glomerular and tubulointerstitial pathologies in kidneys under diabetic conditions. This review summarizes the recent findings regarding the role of autophagy in the pathogenesis of diabetic kidney disease and highlights the regulation of autophagy by the nutrient-sensing pathways and intracellular stress signaling in this disease. The advances in our understanding of autophagy in diabetic kidney disease will facilitate the discovery of a new therapeutic target for the prevention and treatment of this life-threatening diabetes complication.     

外源性干细胞因子对糖尿病胃轻瘫大鼠胃窦Cajal细胞的影响

目的探讨外源性干细胞因子（SCF）能否改善糖尿病胃轻瘫（DGP）大鼠胃窦Cajal细胞（ICC）的异常病变。方法sD大鼠随机分为实验组和对照组，实验组腹腔注射链脲佐菌素（STZ）50mg／kg并高糖高脂饲料不规律喂养构建DGP模型，对照组腹腔注射等量生理盐水并普通饲料规律喂养。成模后随机分为糖尿病组（DM组）、糖尿病＋外源性干细胞因子治疗组（DM＋SCF组）；DM＋SCF纽腹腔注射SCF0．4ug／（kg·d），共15天，对照组和DM纽每天腹腔注射等量的磷酸盐缓冲液（pH=7．4）。RT-PCR、Wester Dblot检测胃窦组织中SCF及c—kit的mRNA及蛋白表达；免疫组化、透射电镜观察胃窦组织中Cajal细胞的变化。结果DM组大鼠胃窦组织SCF及c—kit的mRNA及蛋白表达下降，Cajal细胞数量减少，细胞内线粒体肿胀、内质网扩张；予外源性SCF干预后，胃窦组织中SCF及C—kjf的mRNA及蛋白表达上调，caial细胞数量增多、超微结构明显改善。结论外源性SCF能在一定程度上改善或逆转糖尿病胃轻瘫大鼠胃窦Cajal细胞的异常病变：     

Nicotinamide and streptozotocin diabetes in the rat. Factors influencing the effectiveness of the protection

Summary The effectiveness of nicotinamide in protecting against streptozotocin diabetes does not only depend on streptozotocin dosage but also on the age of the rats. Also, the extent of the protection suddenly decreases when the interval between streptozotocin and nicotinamide injections exceeds 1 h.     

Zur Frage der glomerulären Permeation höhermolekularer Proteine

Summary Haptoglobin and isoagglutinin were found in the urine of diabetic patients, and their renal excretion was higher in patients with diabetic angiopathy. It is concluded from these results (the biological activity of the two polypeptides in urine was intact) that the mechanism of proteinuria can perhaps be explained only by an extension of pores of the renal glomerular filter.     

Isolated rat hepatocytes. Simultaneous study of variations in sialic acid content of glycoconjugated membranes and asialotransferrin uptake]

Hepatocytes isolated from streptozotocin treated Rats bind less asialotransferrin than hepatocytes isolated from normal rats. This decrease is parallel with a decrease in the sialic acid content. Insulin therapy restored simultaneously membrane sialic acid content and asialotransferrin binding capacity.     

解聚复肾宁对糖尿病大鼠肾脏HGF表达的影响

目的观察解聚复肾宁（JJFSN）对糖尿病大鼠肾HGF表达的影响及肾保护作用。方法SD大鼠腹腔注射链尿佐菌素法建立糖尿病模型,随机分为正常对照组、模型组、解聚复肾宁治疗组、依那普利治疗组、JJFSN＋依那普利治疗组。12周后,检测各组空腹血糖（FBG）、尿素（BU）、24h尿β2微球蛋白（β2-MG）、肌酐清除率（Ccr）;免疫组化法检测肾组织HGF表达,放射免疫法测定大鼠血清胰岛素（Ins）含量,透射电镜观察肾脏超微结构。结果与模型组比较,各治疗组大鼠FBG、BU、β2-MG明显降低,Ccr明显升高,血清Ins含量增加,肾组织HGF表达明显上调,肾组织病理变化减轻,其中以J＋Y组改善最显著（P〈0．05）。结论JJFSN对DM大鼠肾脏形态争功能有明显保护作用,其机制可能与其上调肾脏HGF表达、保护胰岛β细胞、延缓肾脏纤维化进程有关。     

Activators of serum lipoprotein lipase in alloxan diabetic rats

Summary The amount of free fatty acid (FFA) liberated with intralipid in post-heparin guinea-pig serum, when serum from alloxan diabetic rat is incubated, is higher than that liberated when serum from healthy rats is used. The above effect is probably due to larger quantities of lipoprotein lipase present in the diabetic serum.     

Testosterone derivatives are neuroprotective agents in experimental diabetic neuropathy

In this study we have assessed the effect of testosterone (T), dihydrotestosterone (DHT) and 5αandrostan-3α, 17β-diol (3α-diol) therapies on diabetic neuropathy. Diabetes was induced in adult male rats by the injection of streptozotocin and resulted in decreased T and increased 3α-diol levels in plasma and in decreased levels of pregnenolone and DHT in the sciatic nerve. Moreover, a reduced expression of the enzyme converting Tinto DHT (i.e., the 5α-reductase) also occurs at the level of sciatic nerve, suggesting that the decrease of DHT levels could be due to an impairment of this enzyme. Chronic treatment for 1 month with DHT or 3α-diol increased tail nerve conduction velocity and partially counteracted the increase of thermal threshold induced by diabetes. Treatment with DHT increased tibial Na⁺,K⁺-ATPase activity and the expression of myelin protein P0 in the sciatic nerve.DHT, 3α-diol and T reversed the reduction of intra-epidermal nerve fiber density induced by diabetes. These observations indicate that T metabolites can reverse behavioral, neurophysiological, morphological and biochemical alterations induced by peripheral diabetic neuropathy. I. Roglio, R. Bianchi: These authors contributed equally to this study. Received 4 January 2007; received after revision 13 February 2007; accepted 27 March 2007     

Effect of niacin/nicotinamide deficiency on the diabetogenic effect of streptozotocin

Summary Weanling CD-1 mice were fed either a control diet or a diet deficient in niacin/nicotinamide for one month and then injected i.v. with 60, 80, 100, 120, 140, or 160 mg/kg streptozotocin. Mice on the deficient diet developed a higher incidence of diabetes and more severe hyperglycemia than those on the control diet.     

Effect of niacin/nicotinamide deficiency on the diabetogenic effect of streptozotocin

Weanling CD-1 mice were fed either a control diet or a diet deficient in niacin/nicotinamide for one month and then injected i.v. with 60, 80, 100, 120, 140, or 160 mg/kg streptozotocin. Mice on the deficient diet developed a higher incidence of diabetes and more severe hyperglycemia than those on the control diet.