灵菊七提取物对糖尿病大鼠治疗作用的实验研究

目的 观察灵菊七提取物对糖尿病大鼠的治疗作用。方法 给大鼠腹腔注射链脲佐菌素，造成糖尿病动物模型，观察不同剂量的灵菊七提取物对正常和糖尿病大鼠体重、血糖、血脂的影响及肾保护作用。结果 灵菊七提取物可显著增加糖尿病大鼠体重，降低血糖，治疗效果优于阳性药物对照组；无明显降血清胆固醇（TC）作用，高剂量组可显著降低甘油三酯（TG）；显著降低糖尿病大鼠Cr、BUN。结论 灵菊七提取物对糖尿病大鼠具一定治疗作用。     

白细胞对早期糖尿病视网膜病变作用的研究

目的探讨白细胞在早期糖尿病大鼠视网膜毛细血管中粘附、堆积及其与视网膜微血管形态学变化的关系。方法健康成年雄性Wistar大鼠90只，随机分成正常对照组和链脲佐菌素（streptozotocin, STZ）诱导的糖尿病组各45只（3、7、14 d组各5只，30、90、180 d组各10只）。取大鼠右眼制备视网膜消化铺片，进行形态学观察及白细胞共有抗原（leukocyte common antigen, CD45）单克隆抗体免疫组织化学研究。结果正常对照组视网膜毛细血管中有少许CD45阳性细胞；糖尿病发生3 d后，CD45的表达明显增加，病程第14 d达高峰，以后基本稳定。病程90 d时，视网膜毛细血管已出现节段性膨大、囊样扩张及闭锁等形态学改变；病程180 d时，上述病变进一步加重。结论白细胞粘附发生在糖尿病视网膜病变（diabetic retinopathy, DR）的早期阶段，是DR在微血管水平病理变化的开端。白细胞粘附可能作为视网膜微血管形态学改变的基础，在DR的发生发展中起着重要作用。(中华眼底病杂志,2003,19:344-347)     

Axonal transport and tissue contents of substance P in rats with long-term streptozotocin-diabetes. Effects of the aldose reductase inhibitor ‘statil’

This study examined the axonal transport of substance P-like immunoreactivity (SPLI) and its content in dorsal root ganglion, trigeminal ganglion, stomach and ileum of non-diabetic rats and two groups of rats with streptozotocin-induced diabetes of 9 months duration. One diabetic group received the aldose reductase inhibitor ‘Statil’ throughout the period of study. To reduce morbidity all diabetic animals were given twice-weekly injections of a long-acting insulin which restricted weight loss but did not prevent regular and severe hyperglycaemia. Axonal transport of SPLI was studied by measurement of accumulation at 12 h ligatures on the left sciatic nerve. There were no differences between the 3 groups either in the calculated anterograde and retrograde mean rates of accumulation (ranges 6.0 to 7.6 and 0.38 to 0.72 mm/h respectively) or mobile fractions of SPLI (means from 0.54 to 0.58). There were, however, marked reductions in anterograde and retrograde accumulations of SPLI in the constricted nerves of the ‘untreated’ diabetics (respectively 57 and 33% of controls;P < 0.01 for both). In the ‘Statil’-treated rats these deficits were attenuated (80 and 75% of controls). Diabetes also reduced the SPLI content of unligated sciatic nerve and trigeminal ganglion (65 and 75% of controls). ‘Statil’ prevented the deficit in the ganglion, but not in the nerve. ‘Statil’ treatment prevented themyo-inositol depletion and attenuated the sorbitol and fructose accumulation seen in the sciatic nerves of the untreated diabetic animals suggesting effective inhibition of aldose reductase in this tissue. The total SPLI content of the stomach and 1-cm segments of ileum were unaltered in the diabetic animals but due to the increased weights of these tissues the SPLI content per unit weight was reduced. These changes were unaffected by ‘Statil’.     

Hepatic changes in the acute phase of streptozotocin (SZ)-induced diabetes in mice

We have reported the streptozotocin (SZ)-induced hepatic lesions in the subacute phase (4 to 12 weeks after the treatment), which are characterized by appearance of oncocytic hepatocytes, cytomegalic hepatocytes and bile duct hyperplasia. In this study, we focused on the acute phase (6 to 48 hours after the treatment) of the SZ-induced hepatic lesions of mice to clarify the onset of the hepatic alterations, especially before the induction of hyperglycemia. Livers were taken from 8-week-old Crj:CD-1 (ICR) male mice at 6,12, 24, 36 and 48 hours after the 200 mg/kg b.w. of SZ-injection. SZ-induced hyperglycemia was noted at 36 and 48 hours after the treatment, but the hepatic changes including lipid peroxidation, mitochondrial swelling, peroxisome proliferation and inhibition of hepatocyte proliferation occurred before the elevation of the serum glucose levels. The present findings indicate the direct effects of SZ on hepatocytes rather than the secondary effects of diabetes, and certain correlations between the hepatocytic changes in the acute phase and those in the subacute one. In addition, ulcer and submucosal edema of the gallbladder were observed at 36 or 48 hours after the SZ-treatment, which can be a novel finding in SZ-treated animal.     

Hypoglycaemic Activity of Nauclea Latifolia Sm. (Rubiaceae) in Experimental Animals

Aqueous, ethanolic and hexane extracts of the leaves of Nauclea latifolia (Rubiaceae) were assessed for their fasting blood glucose lowering effect in normoglycaemic and streptozotocin - diabetic rats. Wistar strain albino rats were given different doses of the extracts after 18 hrs fast and their blood glucose measured at 0,1,2,4 and 6 hours after treatment. The aqueous and ethanolic extracts significantly lowered the fasting blood glucose levels of the STZ-diabetic rats in a dose-dependent manner. The highest dose administered (400mg/kg) lowered the fasting blood glucose of the diabetic rats by 31.7% (aqueous) and 36.1% (ethanolic) extracts. The aqueous extract did not significantly lower the glucose levels of normoglycaemic rats (maximum 6.6%), nor was any significant decrease seen in the rats administered with the hexane (maximum of 4.0% for normoglycaemic and 2.4% for diabetics) extract. The hypoglycaemic and antihyperglycaemic potentials of the aqueous and ethanolic extracts were comparable to that of glibenclamide (1mg/kg).These results further support the traditional use of the plant in the treatment of diabetes mellitus.     

糖尿病小鼠胸主动脉环对血管收缩剂和内皮依赖性舒张剂反应的变化

目的：探讨糖尿病（DM）小鼠在不同时期离体胸主动脉环对血管收缩剂和内皮依赖性舒张剂反应的变化。 方法： 用腹腔注射链脲佐菌素（STZ）40 mg/kg诱导C57BL/6J小鼠产生糖尿病，在17、22和28周分批处死糖尿病和同年龄对照（control）组小鼠，测定其离体胸主动脉环对血管收缩剂：苯肾上腺素（PE）、60 mmol/L KCl的反应及对内皮依赖性舒张剂乙酰胆碱（ACh）的反应。 结果： DM组小鼠2周后空腹血糖≥11.1 mol/L并在整个实验过程中维持这一水平，显著高于control组，而体重显著低于control组；17、22和28周DM组胸主动脉环对PE的反应性分别高于、接近、高于control组，各时期对60 mmol/L KCl都表现高于control组；17、22和28周DM组胸主动脉环对ACh的反应性分别高于、接近、低于control组。 结论： DM组小鼠胸主动脉环对血管收缩剂的反应增强，而内皮功能先代偿性增强，然后降低，表现为内皮损伤。     

Cystometric changes in the early phase of streptozotocin-induced diabetes in rats: evidence for sensory changes not correlated to diabetic neuropathy

Summary 1. The effect of streptozotocin (STZ) induced diabetes on rat urinary bladder function was investigated by means of in vivo cystometry and in vitro recording of bladder strips contractility. A group of sucrose-fed animals was included to determine to what extent the STZ-induced changes were ascribable to the increased diuresis. 2. After 7–9 weeks from STZ injection there was a marked increase in weight of bladder and ureters. Cystometry revealed a marked increase in bladder capacity (volume threshold) although pressure threshold and amplitude of micturition contraction were unaffected. Sucrose-fed animals, having normal blood glucose levels but a similar increase in urine production exhibited cystometric changes identical to those of STZ animals. 3. In vitro experiments indicated that the response to field stimulation (0.1–20 Hz) is reduced in STZ-pretreated but increased in sucrose-fed animals, as compared to controls. 4. The content of urinary bladder and ureters in sensory neuropeptides (substance-P, neurokinin-A and calcitonin-gene related peptide-like immunoreactivity) was increased by STZ diabetes when values were corrected for the increased weight of these organs. 5. The capsaicin-induced contraction of the rat isolated bladder strips, presumably caused by neuropeptides released from intramural sensory nerves, is unaffected by STZ diabetes. 6. These findings indicate that STZ diabetes produces, at an early stage, changes similar to those reported to occur in the human disease, e. g. a greater bladder capacity with unimpaired voiding function. The increased bladder capacity of STZ-rats seems largely, if not solely, ascribable to changes in physical properties of the detrusor muscle, thereby allowing accomodation of greater than normal volumes with similar increase of intraluminal pressure. No sign of diabetic neuropathy of the capsaicin-sensitive sensory nerves can be observed at this stage (7–9 weeks) of STZ diabetes. Send offprint requests to P. Santicioli at the above address     

The effect of streptozotocin-induced diabetes mellitus on urinary excretion of sodium and renal Na+−K+-ATPase activity

Renal sodium handling and microsomal Na⁺–K⁺-ATPase activity in kidney cortex, medulla and papilla of rats with streptozotocin-induced diabetes mellitus (DM) was studied.During 7 days following the administration of streptozotocin GFR, urinary excretion, filtered load and tubular reabsorption of Na⁺ averaged (mean±SE) 1.18±0.016 ml/min, 1.74±0.14, 177.3±8.9 and 175.6±8.9 mEq/min respectively in experimental rats as compared to corresponding rates of 0.85±0.04 (P<0.001), 0.85±0.03 (P<0.001), 129.8±5.8 (P<0.001) and 129±5.8 (P<0.001) respectively in the control rats.The activity of microsomal Na–K-ATPase in the kidney cortex, medulla and papilla of the control group was (mean±SE) 44.7±1.7, 150±7.5 and 37.4±3.6 (moles Pi/mg prot/h) respectively. 24 h after DM induction Na–K-ATPase activity in the cortex rose to 59.3±2.4 (P<0.001) and remained high after 3 and 7 days. Medullary Na–K-ATPase activity was unchanged 24 h after streptozotocin administration but was markedly increased to 260±9 (P<0.001) after 3 days and remained high after 7 days.These findings show that stretozotocin-induced DM in rats causes a substantial increase in GFR which is associated with a net increase in filtered and reabsorbed load of Na⁺ and natriuresis. These alterations are accompanied by a marked increase in Na–K-ATPase activity in renal medulla and in the cortex.This study was supported by the Morton S. Kaufman Hemodialysis Foundation and by the Joint Research Fund of the Hebrew University and Hadassah     

Comparison of in situ hybridization and immunocytochemistry for the detection of residual beta cells in the pancreas of streptozotocin-treated diabetic rats

The relative efficacy of immunocytochemistry versus in situ hybridization in identifying residual beta cells was studied in rats with streptozotocin-induced diabetes. Consecutive sections of pancreas of streptozotocin-treated diabetic rats and control animals were alternately subjected to in situ hybridization (synthetic oligonucleotides complementary to rat preproinsulin mRNA) and immunocytochemistry (monoclonal antibodies to insulin). The results obtained with both methods were quantitated with the use of computer-assisted image analysis, and the ratio of cells positive by immunocytochemistry to those positive by in situ hybridization was determined. Under normoglycaemic conditions the values obtained by immunocytochemistry correlated well with those obtained by in situ hybridization (immuno/in situ > 95%). In the streptozotocin diabetic animals, however, immunocytochemistry resulted in a distinct underestimation of the number of residual beta cells (immuno/in situ < 80%). This difference was even more striking in small islet cell clusters (<100 m) immuno/in situ 20%). These results suggest that in situ hybridization for prohormone mRNA is the method of choice for the identification of residual or regenerating beta cells with very low insulin content. Caution should be used when interpreting quantitative data in diabetic conditions that are based exclusively on immunocytochemical detection methods.     

两种糖尿病肾病大鼠模型的比较

目的 :比较两种糖尿病肾病大鼠模型的优劣。方法 :采用单侧肾切除合并尾静脉注射链尿佐菌素(Streptozotocin ,STZ) (STZ加单侧肾切除组 )及单纯腹腔注射链尿佐菌素 (STZ) (STZ组 )两种方法 ,分别将Wister大鼠造成糖尿病肾病大鼠模型 ,然后检测二种方法在空腹血糖 ,尿 β2 -微球蛋白 (β2 -microglobulin ,β2 -MG)及尿微量白蛋白 (albulin ,Alb)的排出量方面的差异。结果 :STZ组空腹血糖 (33 5 9mmol/L)明显高于STZ加单侧肾切除组 (16 12mmol/L) ;STZ +单侧肾切除组β2 -微球蛋白 ,尿微量白蛋白的排出量较STZ组有明显增加 ,其病理改变也较明显。结论 :STZ合并单侧肾切除更符合糖尿病肾病的病理改变。