糖尿病大鼠肾脏水通道蛋白-2mRNA的表达及黄芪的调节作用

目的观察黄芪注射液(astragalus membranaceus,AM)对链脲佐菌素(streptozotocin,STZ)诱导糖尿病(diabetes mellitus,DM)大鼠肾脏髓质水通道蛋白-2(aquaporin-2,AQP-2)基因表达的影响,以探讨黄芪治疗糖尿病的分子生物学机制。方法实验大鼠分为4组:正常组、糖尿病模型组、AM小剂量组和AM大剂量组,后两组应用AM5、10g·kg-1·d-1腹腔注射6周,测定各组大鼠血糖、血清胰岛素及C肽水平,用代谢笼法测定各组大鼠24h尿量,RT-PCR方法测定各组大鼠肾AQP-2 mRNA的表达。结果糖尿病大鼠血糖水平明显增高,血清胰岛素及C肽水平明显下降,单用黄芪注射液治疗对血糖、血清胰岛素和C肽水平无明显影响,但黄芪治疗可使糖尿病大鼠尿量明显增加。RT-PCR检测发现糖尿病大鼠肾髓质AQP-2 mRNA的表达明显上调,黄芪治疗可使其表达下降。结论黄芪治疗糖尿病利水消肿、改善水平衡代谢紊乱的作用可能与其降低肾髓质AQP-2 mRNA的表达有关。     

紫背天葵提取物对糖尿病肾病大鼠的作用

目的研究紫背天葵提取物对糖尿病肾病大鼠的作用。方法 SD大鼠一次性腹腔注射链脲佐菌素(STZ),建立糖尿病肾病大鼠模型。紫背天葵提取物(5 g/kg)灌胃4周后,收集大鼠24 h尿液,检测尿液中尿蛋白(UP)、N-乙酰β-D-氨基葡萄糖苷酶(NAG)和β2-微球蛋白(β2-MG)的含量;测定肾脏指数;测定血清中尿素氮(BUN)、肌酐(Cr)和β2-MG的含量。结果紫背天葵提取物能明显降低糖尿病肾病大鼠24 h排尿量、尿蛋白、β2-MG和NAG(P<0.01或0.05);使肾脏指数下降(P<0.05);同时能够降低血清中BUN、Cr和β2-MG含量(P<0.01或0.05)。结论紫背天葵提取物可以改善肾脏滤过功能,明显改善糖尿病肾病大鼠临床症状。     

益肾汤对糖尿病大鼠肾组织转化生长因子β_1表达的影响

目的观察中药复方益肾汤对实验性糖尿病(DM)大鼠肾脏的保护作用及对转化生长因子-β1(TGF-β_1)表达的影响,探讨其作用机制。方法用链脲菌素诱发、建立糖尿病大鼠模型,通过益肾汤干预治疗,并以血管紧张素Ⅱ受体阻断剂(ARB)缬沙坦作为对照,观察糖代谢(血糖、胰岛素)、大鼠肾功能[包括:肾重/体重、尿总蛋白(24h)、尿白蛋白(24h)、血尿素氮]、肾小球毛细血管基底膜厚度(GBM)、血及肾组织的TGF-β1表达等指标的变化。结果①成功诱发大鼠DM。②各治疗组与糖尿病未治疗组比较均明显降低糖尿病大鼠血糖、尿素氮、尿总蛋白(24h)及微量白蛋白,升高胰岛素水平,抑制肾皮质TGF-β_1表达及GBM的增厚。③相关分析:肾脏TGF-β_1表达量与尿总蛋白(24h)、尿白蛋白(24h)浓度、GBM厚度呈显著正相关。结论益肾汤具有减少尿微量白蛋白排出、血尿素氮浓度、减少肾脏TGF-β_1表达、延缓GBM增厚的作用;益肾汤防治糖尿病肾病(DN)的作用与ARB相仿。益肾汤防治DN及保护肾功能的作用与其降低肾脏TGF-β_1表达有关。     

Melatonin reduces urinary excretion of N-acetyl-beta-D-glucosaminidase, albumin and renal oxidative markers in diabetic rats

1. Increased oxidative stress has an important role in the pathogenesis of diabetic nephropathy. The aim of the present study was to evaluate diabetic nephropathy by determining markers of oxidative stress and the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), albumin and to investigate the possible protective effects of in vivo melatonin on renal tubular oxidative damage in diabetic rats. 2. Twenty-six rats were randomly divided into three groups: (i) group I, control, non-diabetic rats (n = 9); (ii) group II, untreated diabetic rats (n = 8); and (iii) group III, melatonin-treated diabetic rats (n = 9). In groups II and III, diabetes developed 3 days after administration of a single dose of streptozotocin (35 mg/kg, i.p.). Thereafter, whereas the rats in group II received no treatment, rats in group III began to receive 10 mg/kg per day, i.p., melatonin for 8 weeks. Malondialdehyde (MDA), an index of lipid peroxidation, NAG and microalbumin in the urine, markers of renal tubular damage, were the parameters used for oxidative stress-induced renal injury. Superoxide dismutase (SOD), xanthine oxidase (XO) and glutathione peroxidase (GSH-Px) activities were determined to evaluate changes in the anti-oxidant status of kidney tissue. 3. In untreated diabetic rats, urinary NAG, albumin and renal MDA levels were markedly increased compared with control rats (P < 0.0001). However, these parameters were reduced in diabetic rats by melatonin treatment (P < 0.0001). Urinary excretion of NAG was positively correlated with the microalbuminuria and renal MDA levels (r = 0.8; P < 0.0001). The SOD and XO activities in the untreated diabetic group were found to be significantly higher than those of the control group (P < 0.0001). Superoxide dismutase and XO activities decreased in melatonin-treated rats compared with untreated diabetic rats (P < 0.002 and P < 0.023, respectively). However, the decrease did reach levels seen in control rats. There were no significant differences in GSH-Px activity between the three groups. 4. Therefore, on the basis of these data, we suggest that urinary NAG, albumin excretion, XO activity and MDA levels are more valuable parameters showing the degree of renal tubular injury than classical markers of oxidative stress, including SOD and GSH-Px, in diabetic rat kidneys. Melatonin has an ameliorating effect on oxidative stress-induced renal tubular damage via its anti-oxidant properties. Thus, it may be suggested that urinary NAG excretion and microalbuminuria may be important markers showing the degree of renal changes and the success of long-term treatment of renal impairment with melatonin.     

保肾降糖胶囊对糖尿病大鼠降糖及肾保护作用研究

目的：探讨保肾降糖胶囊对糖尿病大鼠肾脏的保护作用及其机制。方法：将SD大鼠分为6组,测定第1、8周血清肌酐及血清胰岛素、胰高血糖素、糖化血红蛋白等生化指标和尿液各项指标;取肾上腺皮质测定SOD、GSH-Px、MDA、NO2-/NO3-和NOS,评价保肾降糖胶囊的降糖作用及对糖尿病肾病的保护作用。结果：给药保肾降糖胶囊60d后,高剂量组和中剂量组大鼠的血糖值明显降低,血清肌酐清除率显著增加,尿微量清蛋白排泄率明显降低,血清胰岛素明显升高,胰高血糖素、糖化血红蛋白、尿微量清蛋白均显著降低;肾上腺皮质中的T-SOD、GSH-Px、NO^2-/NO^3-、NOS含量增加,MDA含量显著降低。结论：保肾降糖胶囊可降低糖尿病大鼠的血糖,明显减轻糖尿病大鼠蛋白尿,改善肾小球滤过率。通过提高抗氧化酶活性、清除ROS、增加NOS活性从而延缓肾小球硬化进程,减轻糖尿病肾病并发症。     

氨基胍对糖尿病大鼠肾损害的治疗作用

目的通过探讨氨基胍（AG）对早期糖尿病（DM）大鼠一氧化氮（NO）、一氧化氮合酶（ni-tric oxi desynthase,NOS）活性及24h尿蛋白排泄量（24hUPE）的影响,了解氨基胍对糖尿病肾病的治疗作用。方法健康清洁级Wistar大鼠40只,检测24hUPE、血清NO水平、总一氧化氮合酶（total nitric oxide synthase,tNOS）和诱导型一氧化氮合酶（inducible nitric oxide synthase,iNOS）及结构型一氧化氮合酶（constructive nitric oxide synthase,cNOS）活性等5项指标后,用链脲佐菌素（Streptozotocin,STZ）60mg/kg制备成糖尿病大鼠模型,将糖尿病鼠随机分为糖尿病对照组、氨基胍组（AG组）。于8周末时再检测大鼠的上述5项指标并进行统计分析。结果①与造模前比较,DM对照组在8周末时24hUPE、NO和iNOS升高（P〈0.01,P〈0.05）;AG组24hUPE增加（P〈0.01）,tNOS、iNOS、cNOS降低（P〈0.01,P〈0.05）。②与DM对照组比较,8周末时AG组5项指标均下降（P〈0.05）。结论在糖尿病肾病（DN）的发展进程中,早期阶段应用AG可通过降低血NOS活性、NO生成量及其他机制,使24hUPE减少,减轻肾脏的损害。     

Hypoglycemic activity of Eugenia jambolana and Ficus bengalensis: mechanism of action.

The extract of jaman pulp from fruit of Eugenia jambolana showed hypoplycemic activity. This report is the first evidence of such activity in relation to pulp. The effect of pulp was seen in 30 min, while the seeds of the same fruit required 24 hr. The extracts of bark of Ficus bengalensis caused reduction in blood sugar level. These results were confirmed in streptozotocin-induced diabetic animals. The oral administration of the extract resulted in enhancement in serum insulin levels in normoglycemic and diabetic rats. The incubation of isolated islets of Langerhans from normal as well as from diabetic animals with each of these plant extracts stimulated insulin secretion. These extracts inhibited insulinase activity from liver and kidney.     

Effects of insulin treatment on heart rhythm, body temperature and physical activity in streptozotocin-induced diabetic rat

1. Streptozotocin (STZ)-induced diabetic cardiomyopathy is frequently associated with depressed diastolic/systolic function and altered heart rhythm. 2. The effects of insulin treatment on heart rhythm, body temperature and physical activity in STZ-induced diabetic rats were investigated using biotelemetry techniques. 3. Transmitter devices were surgically implanted in the peritoneal cavity of young adult male Wistar rats. Electrodes from the transmitter were arranged in Einthoven bipolar - Lead II configuration. Electrocardiogram, physical activity and body temperature data were recorded with a telemetry system for 10 days before STZ treatment, for 20 days following administration of STZ (60 mg/kg) and thereafter, for 30 days while rats received daily insulin. 4. Heart rate, physical activity and body temperature declined rapidly 3-5 days after administration of STZ. Pre-STZ heart rate was 362 +/- 7 b.p.m., falling to 266 +/- 12 b.p.m. 5-15 days after STZ with significant recovery to 303 +/- 14 b.p.m. 10-20 days after commencement of insulin. Pre-STZ body temperature was 37.5 +/- 0.1C, falling to 37.2 +/- 0.2C 5-15 days after STZ with significant recovery to 37.5 +/- 0.1C 10-20 days after commencement of insulin. Physical activity and heart rate variability were also reduced after STZ but there was no significant recovery during insulin replacement. 5. Defective autonomic regulation and/or mechanisms of control that are intrinsic to the heart may underlie disturbances in heart rhythm in the STZ-induced diabetic rat.     

Effects of Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) on hyperglycemia in streptozotocin-induced diabetic rats

The present study investigated the effects of Hachimi-jio-gan (HJ) on diabetic hyperglycemia in streptozotocin (STZ)-induced diabetic rats. After STZ administration, rats had free access to pellets containing 1% HJ extract powder for four weeks. HJ markedly suppressed hyperglycemia in STZ-induced diabetic rats at three and four weeks after the start of administration. There were also significant increases in serum and pancreatic immunoreactive insulin levels in STZ and HJ co-administering rats. However, in the present study, the number of beta cells in the pancreatic Langerhans' islets did not increase. Next, in order to investigate the action mechanism besides the glycemic control action of insulin, the expression of glucose transporter 2 (GLUT2) protein, which is involved in glucose uptake and release in the liver, was investigated. GLUT2 protein expression was increased by STZ administration but was normalized after four weeks of HJ administration. Therefore, irrespective of the structural changes in pancreatic beta-cells due to STZ, HJ increased insulin production and secretion by the pancreas and significantly suppressed GLUT2 synthesis in the liver. Amylase secretion from the pancreas was measured to assess pancreatic secretion. Amylase activity was decreased by STZ but was increased by HJ. Therefore, the effects of HJ on STZ-induced hyperglycemia in rats could be summarized as follows: besides increasing insulin synthesis and release, HJ normalizes GLUT2 protein expression in the liver to suppress hyperglycemia. Hence, the results of the present study suggest for the first time that HJ affects not only the production and secretion of insulin, but also the release of glucose from the liver.     

Enzymes of renal origin in urine as indicators of nephrotoxicity.

One of the first ultrastructural changes seen after treatment with many nephrotoxins is sloughing of proximal tubule brush borders. Maltase and alkaline phosphatase in the kidney are localized in the brush border of the proximal tubule. Thus, increased activity of these enzymes in the urine should follow sloughing of brush border into the urine. The object of this investigation was to test the hypothesis that, following treatment with known nephrotoxins, increased urinary maltase and alkaline phosphatase activities could be measured prior to the development of other signs of nephrotoxicity. Male Sprague-Dawley rats were treated with HgCl₂ (1 mg/kg), K₂Cr₂O₇ (15 mg/kg), or saline, ip. Total enzyme activity was determined in fresh (maltase) or dialyzed (alkaline phosphatase) urine. Maltase and alkaline phosphatase activities were both elevated in the 0- to 4-hr urine samples after K₂Cr₂O₇. After HgCl₂, increased enzymuria first occurred at 9–24 hr. In both cases, these effects appeared to be reversible, returning to control values by 48 hr. Urine enzymes and blood urea nitrogen (BUN) were compared 24 hr after several doses of HgCl₂. Urinary enzyme activity was significantly increased after 1 mg/kg, before BUN was increased (2 mg/kg). After K₂Cr₂O₇, uranyl acetate, neomycin, folic acid, and carbon tetrachloride, BUN was increased without affecting urinary enzyme activity or at the same dose that increased enzyme excretion. Thus, it appears that increased activities of maltase and alkaline phosphatase in the urine could be used as noninvasive, nondestructive indexes of renal damage, but may be no more sensitive than methods currently available.     

Influence of umbelliferone on membrane-bound ATPases in streptozotocin-induced diabetic rats

The activities of membrane-bound ATPases are altered both in erythrocytes and tissues of streptozotocin (STZ)-induced diabetic rats and diabetic patients. Umbelliferone (UMB), a natural antioxidant, is a benzopyrone occurring in nature, and it is present in the fruits of golden apple (Aegle marmelos Correa) and bitter orange (Citrus aurantium). Earlier we evaluated and reported the effect of UMB on plasma insulin and glucose, and this study was designed to evaluate the effect of umbelliferone on membrane-bound ATPases in erythrocytes and tissues (liver, kidney and heart) of STZ-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 180-200 g, were made diabetic by an intraperitonial administration of STZ (40 mg/kg). Normal and diabetic rats were treated with UMB dissolved in 10% dimethyl sulfoxide (DMSO) and diabetic rats were also treated with glibenclamide as drug control, for 45 days. In our study, diabetic rats had increased level of blood glucose and lipid peroxidation markers, and decreased level of plasma insulin and decreased activities of total ATPases, (Na(+)+K(+))-ATPase, low affinity Ca(2+)-ATPase and Mg(2+)-ATPase in erythrocytes and tissues. Restoration of plasma insulin and glucose by UMB and glibenclamide seemed to have reversed insulin, glucose and lipid peroxidation markers, and diabetes-induced alterations in the activities of membrane-bound ATPases. Thus, our results show that the normalization of membrane-bound ATPases in various tissues, is due to improved glycemic control and antioxidant activity by UMB.     

Protective effect of Umbelliferone on membranous fatty acid composition in streptozotocin-induced diabetic rats

Umbelliferone (UMB), a natural antioxidant, is benzopyrone in nature, and it is present in the fruits of golden apple and bitter orange. Earlier we evaluated and reported the effect of Umbelliferone on antidiabetic, antioxidant and antihyperlipidemic properties, and this study was designed to evaluate the effect of Umbelliferone on membrane fatty acid composition and histopathology of liver and kidney of control and streptozotocin (STZ) diabetic rats. Male albino Wistar rats (180-200 g) were made diabetic by an intraperitonial administration of STZ (40 mg/kg). The control and diabetic rats were treated with Umbelliferone and glibenclamide dissolved in 10% dimethyl sulfoxide for 45 days. Diabetic rats had decreased insulin and increased glucose, and increased levels of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes. The levels of palmitic, stearic and oleic acids increased and the levels of linolenic and arachidonic acids decreased in diabetic rats as compared with control rats. Thus, the saturated fatty acids and monounsaturated fatty acids increased and the polyunsaturated fatty acids decreased in diabetic rats. Diabetic rats had decreased liver weight and increased activities of alanine transaminase and aspartate transaminase; increased kidney weight and urine albumin, and decreased levels of urea, uric acid and creatinine in the urine. Histopathological studies of liver and kidney in diabetic rats showed fatty changes surrounding portal triad; enlargement of lining cells of tubules, fatty infiltration, large area of hemorrhage and lymphocyte infiltration. Treatment with Umbelliferone and glibenclamide reversed these changes to near normalcy. Our results showed that Umbelliferone has a protective effect on membrane fatty acid composition of liver and kidney as supported by antioxidant and antihyperlipidemic effects of Umbelliferone reported earlier as evidenced by improved histopathological changes, hepatic and nephritic markers, indicating recovery from the risk of diabetic complications.     

Insulin-induced immunohistochemical and morphological changes in pancreatic beta-cells of streptozotocin-treated diabetic rats

This study was undertaken to investigate insulin-induced changes in the immunohistochemistry and morphometry of pancreatic beta-cells, plasma insulin and blood glucose concentrations of streptozotocin (STZ)-treated diabetic rats. Fifty male Wistar rats (200-250 g) were randomly divided into three experimental groups (viz., A: control group, B: STZ-treated group, and C: STZ+insulin-treated group). Diabetes was induced in group B and group C rats by single intraperitoneal injections of STZ (75 mg/kg body weight), while each animal in the "control" group A received equal volume of citrate buffer solution (pH 6.3) intraperitoneally. STZ+insulin-treated group C diabetic rats were additionally treated with subcutaneous injections of lente insulin (0.5 U/kg body weight) daily from Day 10 to Day 30 of our 40-day study period. The rats used were sacrificed at different time intervals (10th, 20th, 30th and up to the 40th day) following STZ treatment. Fragments of endocrine pancreas of each rat were randomly processed for immunohistochemistry staining and pancreatic insulin content. In diabetic state, pancreatic beta-cells showed a weak immunostaining for insulin on Day 10. Thereafter, insulin administration (in the group C rats) caused a significant decrease (p < 0.05) in the elevated blood glucose levels, and a significant increase (p < 0.05) in the serum insulin concentrations. The surviving beta-cells regenerated and virtually regained their normal immunostaining and functional status for insulin. On the 30th day, the pancreatic insulin contents of the insulin-treated group C rats showed approximately 45-fold increase in immunoreactivity when compared with the immunoreactivity of the same STZ+insulin-treated rats on Day 10 of the 40-day study period. The present study illustrates the sequence of morphological changes that occur in the islets of Langerhans following STZ administration and subsequent insulin treatment. The study also suggests that administration of a moderate single dose of STZ in Wistar rats produces specific necrosis of beta-cells, typical of type 1 insulin-dependent diabetes. The experimental evidence obtained in this study appears to suggest that induction of regenerative stimulus (by insulin treatment) in diabetic state triggers pancreatic regenerative processes, thereby restoring functional activities of the pancreas.     

Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and beta-cell damage in rat pancreas.

The aim of the present study was the evaluation of possible protective effects of quercetin (QE) against beta-cell damage in experimental streptozotocin (STZ)-induced diabetes in rats. STZ was injected intraperitoneally at a single dose of 50 mg kg(-1) for diabetes induction. QE (15 mg kg(-1) day, intraperitoneal (i.p.) injection) was injected for 3 days prior to STZ administration; these injections were continued to the end of the study (for 4 weeks). It has been believed that oxidative stress plays a role in the pathogenesis of diabetes mellitus (DM). In order to determine the changes of cellular antioxidant defense system, antioxidant enzymes such as glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and catalase (CAT) activities were measured in pancreatic homogenates. Moreover we also measured serum nitric oxide (NO) and erythrocyte and pancreatic tissue malondialdehyde (MDA) levels, a marker of lipid peroxidation, if there is an imbalance between oxidant and antioxidant status. Pancreatic beta-cells were examined by immunohistochemical methods. STZ induced a significant increase lipid peroxidation, serum NO concentrations and decreased the antioxidant enzyme activity. Erythrocyte MDA, serum NO and pancreatic tissue MDA significantly increased (P < 0.05) and also the antioxidant levels significantly decreased (P < 0.05) in diabetic group. QE treatment significantly decreased the elevated MDA and NO (P < 0.05), and also increased the antioxidant enzyme activities (P < 0.05). QE treatment has shown protective effect possibly through decreasing lipid peroxidation, NO production and increasing antioxidant enzyme activity. Islet cells degeneration and weak insulin immunohistochemical staining was observed in STZ induced diabetic rats. Increased staining of insulin and preservation of islet cells were apparent in the QE-treated diabetic rats. These findings suggest that QE treatment has protective effect in diabetes by decreasing oxidative stress and preservation of pancreatic beta-cell integrity.     

Quercetin, an anti-oxidant bioflavonoid, attenuates diabetic nephropathy in rats

1. Diabetic nephropathy is an important microvascular complication and one of the main causes of end-stage renal disease. Many in vivo and in vitro studies have indicated that oxidative stress is one of the major pathophysiological mechanisms involved in the development of diabetic nephropathy. In the present study, we examined the effect of an anti-oxidant bioflavonoid quercetin on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. 2. Diabetes was induced in Sprague-Dawley rats with a single intravenous injection of STZ (45 mg/kg). Four weeks after STZ injection, quercetin (10 mg/kg per day) was given orally for 4 weeks in both control and diabetic rats. Plasma glucose levels and bodyweights were measured at 4 and 8 weeks after the STZ injection. At the termination of the experiments, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. The renal oxidative stress marker malonaldehyde, glutathione levels and the anti-oxidant enzymes superoxide dismutase and catalase were measured in kidney homogenate. 3. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria, proteinuria and a decrease in bodyweight compared with age-matched control rats. After 8 weeks, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance, and proteinuria along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key anti-oxidant enzymes. Treatment with quercetin significantly attenuated renal dysfunction and oxidative stress in diabetic rats. 4. These results confirm the role of oxidative stress in the development of diabetic nephropathy and point to the possible anti-oxidative mechanism being responsible for the nephroprotective action of quercetin.     

The influences of endogenous bile acids on maltase and alkaline phosphatase activities in intrahepatic cholestasis rats

The activities of lysosomal maltase in the serum, bile and liver were determined in intrahepatic cholestasis rats induced by alpha-naphtylisothiocyanate (ANIT, 200 mg/kg, i.p.), and compared with changes in alkaline phosphatase (ALP) activity. Moreover, the influences of endogenous bile acids on the release of maltase activity from the liver in intrahepatic cholestasis rats were studied. The maltase activities in the serum and bile significantly increased from 4 and 8 h after the intraperitoneal administration of ANIT, respectively. Conversely, a significant decrease in liver maltase activity was observed from 4 h after the injection of ANIT. On the other hand, total bile acid concentrations in the serum and bile significantly increased immediately after the treatment of ANIT, when biliary bile acid, exogenous bile acid or Triton X-100 was added to lysosomal fraction in the liver, the maltase activity in the supernate after the reaction significantly increased in proportion to the concentration of each substance added to the liver lysosome. These results suggested that maltase might be released from liver lysosomal membrane by surface active-action of bile acid accumulated in the liver after the administration of ANIT. Moreover, the changes in ALP activities in the serum, bile and liver after the administration of ANIT were almost similar to those in maltase activity.     

yy大黄酸对糖尿病大鼠肾脏还原型辅酶Ⅱ基因表达的影响

目的 观察大黄酸对糖尿病大鼠肾脏氧化应激的影响.方法链脲佐菌素(STZ)诱导的糖尿病肾病大鼠模型随机分为模型组与治疗组,治疗6周后,比较各组大鼠肾组织中丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性,同时检测各组大鼠血糖、血肌酐、尿素氮、24 h尿蛋白定量等.采用逆转录-聚合酶链反应(RT-PCR)方法检测p22phox及p47phox的表达.结果治疗组较模型组明显改善尿清蛋白、尿素氮水平和肾脏肥大指数.肾脏MDA含量明显下降(P<0.05),SOD活性显著上升(P<0.05).与对照组比较,模型组p47phox和p22phox mRNA表达明显增多,大黄酸干预使其表达明显降低.结论大黄酸对2型糖尿病肾脏病变有一定的保护作用,其机制可能是通过抑制氧化应激反应,下调糖尿病大鼠p22phox及p47phox的表达对2型糖尿病模型大鼠肾脏产生保护作用.     

The influence of rutin on the extracellular matrix in streptozotocin-induced diabetic rat kidney

We previously reported that rutin administration to streptozotocin (STZ)-induced diabetic rats decreased plasma glucose and increased plasma insulin levels. In this study, we have examined the role of rutin on matrix remodelling in the kidney of STZ-induced diabetic rats. STZ was administered intraperitoneally (50 mg kg(-1)) to male albino Wistar rats to induce experimental diabetes. Rutin (100 mg kg(-1)) was orally administered to normal and STZ-induced diabetic rats for a period of 45 days and its influence on the content of hydroxyproline and collagen and on the activity of matrix metalloproteinases (MMPs) were studied. We have also studied the levels of tissue inhibitors of metalloproteinases (TIMPs) in the kidney. STZ-induced diabetic control rats showed increased content of hydroxyproline and collagen, decreased activity of MMPs and increased levels of TIMPs in the kidney. These changes were positively modulated by rutin treatment in STZ-induced diabetic rats, thereby protecting the kidney. In normal rats treated with rutin, none of the parameters studied were significantly altered. From the results obtained, we could conclude that rutin influences MMPs and effectively protects kidney against STZ-induced damage in rats. The effects observed are due to the reduction of plasma glucose levels by rutin.     

Effect of streptozotocin-induced hyperglycaemia on intravenous pharmacokinetics and acute cardiotoxicity of doxorubicin in rats.

The present study was designed to investigate the pharmacokinetics and acute cardiotoxicity of doxorubicin (DOX) after intravenous (i.v.) administration (15 mg kg(-1)) to streptozotocin (STZ)-induced hyperglycaemic and normoglycaemic male Wistar albino rats. In STZ diabetic rats the area under the serum DOX time-concentration curve (AUC(0-24 h)) increased (13.35+/-1.33 compared with 7.13+/-0.71 microg h(-1) ml(-1); P<0.0001) and plasma and renal DOX clearance decreased. The DOX accumulation in STZ-induced diabetic rat heart (12.7+/-1.2 microg g(-1)) was increased (P<0.05) compared with non-diabetic hearts (11.0+/-0.9 microg/g), 24 h after DOX administration. Serum creatine phosphokinase (CPK) activity showed 25% increase in peak level in STZ diabetic rats compared to non-diabetic rats. DOX produced a reduction in heart rate of anaesthetized non-diabetic (20%) and diabetic (14%) rats 1 and 2 h after its administration, respectively. Isolated atria of diabetic rats were more sensitive to the negative chronotropic effect of DOX (150 microm). These preliminary results indicate that hyperglycaemia may alter the pharmacokinetics and acute cardiotoxicity of DOX and suggest that i.v. doses of DOX in diabetic patients may need to be modified if the present data could be extrapolated to humans.     

Metabolic alterations in normal and streptozotocin-diabetic rats in vivo: influence of prolonged starvation

We studied the influence of prolonged starvation on carbohydrate metabolism in streptozotocin-diabetic rats compared with normal rats. In streptozotocin (STZ)-diabetic rats, the plasma glucose concentration decreased gradually during prolonged starvation, while it did not change in normal rats. In normal rats, glycogen depletion in the liver occurred within 24 hr of starvation, while in STZ-diabetic rats, glycogen content did not change even after 72 hr of starvation. Impaired glucose tolerance and glycogen deposition in response to oral administration of glucose were observed in STZ-diabetic rats compared with normal animals. STZ-diabetic animals generally had lower glycogen synthase and phosphorylase activities compared with normal rats during starvation. In normal animals, there is a significant correlation between the plasma concentration of free fatty acids and 3-hydroxybutyrate. On the basis of these findings, metabolic alterations in chemically-induced diabetic animals were discussed.