Time-dependent changes of calbindin D-28K and parvalbumin immunoreactivity in the hippocampus of rats with streptozotocin-induced type 1 diabetes

The hippocampus is affected by various stimuli that include hyperglycemia, depression, and ischemia. Calcium-binding proteins (CaBPs) have protective roles in the response to such stimuli. However, little is known about the expression of CaBPs under diabetic conditions. This study was conducted to examine alterations in the physiological parameters with type 1 diabetes induced with streptozotocin (STZ) as well as time-dependent changes in the expression of two CaBPs changes of were being evaluated. Rats treated with STZ (70 mg/kg) had high blood glucose levels (>21.4 mmol/L) along with increased food intake and water consumption volumes compared to the sham controls. In contrast, body weight of the animals treated with STZ was significantly reduced compared to the sham group. CB-specific immunoreactivity was generally increased in the hippocampal CA1 region and granule cell layer of the dentate gyrus (DG) 2 weeks after STZ treatment, but decreased thereafter in these regions. In contrast, the number of PV-immunoreactive neurons and fibers was unchanged in the hippocampus and DG 2 weeks after STZ treatment. However, this number subsequently decreased over time. These results suggest that CB and PV expression is lowest 3 weeks after STZ administration, and these deficits lead to disturbances in calcium homeostasis.     

Changes in glial fibrillary acidic protein immunoreactivity in the dentate gyrus and hippocampus proper of adult and aged dogs

Astrocytes perform neuron-supportive tasks, repair and scarring process in the central nervous system. In this study, we observed glial fibrillary acidic protein (GFAP), a marker for astrocytes, immunoreactivity in the dentate gyrus and hippocampus proper (CA1-3 region) of adult (2-3 years of age) and aged (10-12 years of age) dogs. In the adult group, GFAP immunoreactive astrocytes were distributed in all layers of the dentate gyrus and CA1-3 region, except in the stratum pyramidale of the CA1-3 region. In the aged group, GFAP immunoreactivity decreased markedly in the molecular layer of the dentate gyrus. However, GFAP immunoreactivity in the CA1-3 region increased in all layers, and the cytoplasm of GFAP immunoreactive astrocytes was hypertrophied. GFAP protein levels in the aged dentate gyrus decreased; however, GFAP levels in the CA1-3 region increased. These results suggest that the morphology of astrocytes and GFAP protein levels in the hippocampal dentate gyrus and CA1 region are changed, respectively, with age.     

Sequential alterations of glucocorticoid receptors in the hippocampus of STZ-treated type 1 diabetic rats

Type 1 diabetes is a common metabolic disorder accompanied by increased blood glucose levels along with glucocorticoid and cognitive deficits. The disease is also thought to be associated with environmental changes in brain and constantly induces oxidative stress in patients. Therefore, glucocorticoid-mediated negative feedback mechanisms involving the glucocorticoid receptor (GR) binding site are very important to understand the development of this disease. Many researchers have used streptozotocin (STZ)-treated diabetic animals to study changes in GR expression in the brain. However, few scientists have evaluated the hyperglycemic period following STZ exposure. In the present study, we found GR expression in the hippocampus varied based on the period after STZ administration for up to 4 weeks. We performed immunohistochemistry and Western blotting to validate the sequential alterations of GR expression in the hippocampus of STZ-treated type 1 diabetic rats. GR protein expression increased significantly until week 3 but decreased at week 4 following STZ administration. GR expression after 70 mg/kg STZ administration was highest at 3 weeks post-treatment and decreased thereafter. Although STZ-induced increase in GR expression in diabetic animals has been described, our data indicate that researchers should consider the sequential GR expression changes during the hyperglycemic period following STZ exposure.     

N-acetylserotonin increases cell proliferation and differentiating neuroblasts with tertiary dendrites through upregulation of brain-derived neurotrophic factor in the mouse dentate gyrus

In this study, we investigated the effects of N-acetylserotonin (NAS) on cell proliferation and neuroblast differentiation in the mouse dentate gyrus using anti-Ki67 and anti-doublecortin (DCX) antibodies. Ki67 is expressed in the nucleus or on the surface of chromosomes during all of the active phases of the cell cycle, and DCX is expressed in neuronal precursor cells as well as in immature neurons. At 17 weeks of age, 20 mg/kg of NAS or the same volume of vehicle was intraperitoneally administered once a day for 3 weeks. The animals were sacrificed 2 hr after the last vehicle or NAS treatment. NAS treatment significantly increased the number of Ki67-positive nuclei and DCX-immunoreactive neuroblasts with well-developed dendrites (tertiary dendrites) compared to the vehicle-treated group. However, the number of DCX-immunoreactive neuroblasts without tertiary dendrites was not changed. The administration of NAS also significantly increased the protein levels of brain-derived neurotrophic factor (BDNF) in the dentate gyrus. This result suggests that NAS significantly promotes cell proliferation and the number of differentiating neuroblasts with tertiary dendrites through an increase in BDNF levels in the mouse dentate gyrus.     

Changes of calbindin D-28k immunoreactivity in the hippocampus after adrenalectomy in the seizure sensitive gerbil

Calbindin D-28k (CB), a calcium-binding protein, containing neurons in the hippocampus plays an important role in hippocampal excitability in epilepsy. In the present study, we investigated changes of CB immunoreactivity after adrenalectomy (ADX) in the hippocampus and dentate gyrus of the seizure sensitive gerbil, which is susceptible to seizure to identify roles of CB in epileptogenesis. The changes of the CB immunoreactivity after ADX were significant in the hippocampal CA1 region. By 24 h after ADX, CB-immunoreactive CA1 pyramidal cells and CB immunoreactivity increased. At this time, well-stained dendrites projected to the stratum radiatum. Thereafter, the CB immunoreactivity decreased time dependently by 96 h after ADX. In the dentate gyrus, the changes of CB-immunoreactive neurons were mainly observed in the granule cell layer. The number and immunoreactivity of CB-immunoreactive neurons was high at 24 h after ADX, thereafter, those decreased by 96 h after ADX. These results suggest that glucocorticoid has an important role in modulating the seizure activity and CB serves an inhibitory function, which regulates the seizure activity and output signals from the hippocampus.     

Effects of s-allyl-L-cysteine on cell proliferation and neuroblast differentiation in the mouse dentate gyrus

In this study, we investigated the effects of S-allyl-L-cysteine (SAC), a major sulfur-containing compound present in garlic, on Ki67- and doublecortin (DCX)-positive cells, which were used as a marker for cell proliferation and neuroblast differentiation, respectively, in the mouse dentate gyrus. SAC (300 mg/kg) was intraperitoneally administered to 8-week-old mice once a day for 3 weeks. The animals were then sacrificed at 11 weeks of age. SAC administration significantly increased Ki67-positive nuclei and DCX-immunoreactive neuroblasts in the subgranular zone of the dentate gyrus. Furthermore, serotonin 1A receptor (5-HT(1A)) levels in the hippocampus were also increased. These results suggest that SAC significantly increased cell proliferation and neuroblast differentiation by increasing 5-HT(1A) levels in the dentate gyrus.     

Differential effects of treadmill exercise on calretinin immunoreactivity in type 2 diabetic rats in early and chronic diabetic stages

In this study, we investigated the effects of treadmill exercise on calretinin (CR), a marker of early postmitotic neurons, immunoreactivity in the dentate gyrus (DG) of Zucker diabetic fatty (ZDF) rats, before or after diabetes onset, and Zucker lean control (ZLC) rats. For this study, 6-week-old ZLC and prediabetic ZDF rats, and 22-week-old ZLC and ZDF rats were exercised on the treadmill. Sedentary ZLC and ZDF rats of the same age were used as exercise experiment controls. The exercised prediabetic ZDF rats did not show diabetes onset, while the sedentary prediabetic ZDF rats showed significantly increased blood glucose levels. The exercised diabetic ZDF rats exhibited a decrease in their blood glucose levels compared to the sedentary diabetic ZDF rats, but the levels were still above 20 mmol/l. ZLC rats of both ages were in the normoglycemic range. CR immunoreactivity was detected throughout the DG, including the subgranular zone and the polymorphic layer. Diabetic rats exhibited a significant decrease in the number of CR-immunoreactive cells and fibers in the DG. Exercise in the prediabetic ZDF rats significantly increased the number of CR-immunoreactive cells and fibers in the subgranular zone of the DG. In the ZLC and ZDF rats of chronic diabetic phase, exercise increased CR-immunoreactive neurons in the hilar region. These results suggest that diabetes significantly reduces the number of postmitotic CR-immunoreactive neurons and the intensity of immunoreactivity and that exercise increases these CR-related parameters in a diabetic stage-dependent manner.     

Effect of 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, on parvalbumin immunoreactivity after cerebral ischaemia in the hippocampus of the Mongolian gerbil

Previous studies have demonstrated that a loss of parvalbumin-immunoreactive (PV-ir) neurones is observed in the hippocampus after transient cerebral ischaemia. However, whether the loss of parvalbumin (PV) immunoreactivity is related to the over-production of nitric oxide (NO) during cerebral ischaemia has not been evaluated. This study was designed to test the effect of 7-nitroindazole pre-treatment (7-NI, 50 mg/kg), a selective neuronal NO synthase inhibitor, on PV immunoreactivity and its cellular activity following forebrain ischaemia. PV-ir neurones in the hippocampus of the control group were widely distributed in the pyramidal cell layer and stratum oriens of CA1 and CA3, and the granular cell layer of dentate gyrus. 7-NI pre-treatment completely suppressed the reduction of PV immunoreactivity in CA1 that was observed in the ischaemia-induced group. Subsequently, 7-NI pre-treatment also protected against the structural loss of microtubule-associated protein 2 (MAP2) immunoreactivity in CA1 after ischaemic insult. In addition, the Fos-defined neuronal activity of PV-ir neurones was slightly increased by the 7-NI pre-treatment 3 h after ischaemia. Based on these data, we conclude that the neuronal toxicity of NO may be involved in the loss of PV-ir neurones after cerebral ischaemia.     

The enhanced expression of c-Jun immunoreactivity in the adrenalectomized gerbil hippocampus

Recent in vitro and in vivo studies have shown that glucocorticoids have a profound influence on the survival of hippocampal neurones, and that the depletion of glucocorticoids as a result of adrenalectomy (ADX) reduces nerve growth factor levels in the hippocampus. It is also believed that ADX is associated with the seizure susceptibility of the Mongolian gerbil. In the present study, the choronological changes of c-jun immunoreactivity were investigated after ADX in the hippocampal formations in the seizure-prone gerbil model. In the sham hippocampus, c-jun immunoreactivity was not observed in the neurones of the hippocampus proper and dentate gyrus. C-jun immunoreactive neurones appeared 3 h after ADX in the neurones of the CA1 area and dentate gyrus, and these immunoreactivities peaked 24 h after ADX and then gradually decreased. These results suggest that, in the adrenalectomized gerbil, c-jun may be expressed in the neurones of the hippocampus in compensation for glucocorticoid deficit. The result of enhanced c-jun expression of the hippocampal formation provides anatomical support for the hypothesis that c-jun may play a role in the reduction of seizure activity.     

SD大鼠2型糖尿病模型的建立及相关指标的测定

通过链脲佐菌素(STZ)结合高糖高脂饮食诱导建立2型糖尿病大鼠模型。30只健康雄性SD大鼠随机分为模型组(20只)、空白组(10只)。模型组喂饲高糖高脂饲料4周后,用STZ 30mg/kg一次性左下腹腔注射。检测试验第1周、第4周,注射STZ后第1周、第4周、第8周、第12周空腹体重、血清葡萄糖(BG)、甘油三酯(TG)、胆固醇(TC)、胰岛素(INS)、葡萄糖依赖性促胰岛素释放肽(GIP)、胰岛素样生长因子1(IGF-1)、胰高血糖素样多肽-1(GLP-1)等指标,进行统计分析。处死大鼠,取胰腺进行病理切片检查。动物成模率为75%。试验第4周,模型组TG、TC值明显升高,与空白组比较,P<0.01。注射STZ后第1、4、8、12周,模型组BG、TG、TC值均明显升高,与空白组比较,P<0.01;ISI均明显降低,与空白组比较,P<0.01。注射STZ后第1、4、8周,模型组的GLP-1、IGF-1值明显降低,与空白组比较,P<0.01。注射STZ后第12周,模型组的GLP-1、GIP、IGF-1值明显降低,与空白组比较,P<0.01。试验结果表明,STZ一次性左下腹腔注射结合高糖高脂饮食可成功诱导2型糖尿病大鼠模型。GIP、IGF-1、GLP-1等细胞因子参与了2型糖尿病的病理发生。     

补中益气丸对糖尿病大鼠胃组织MUC1、COX、NOS表达变化及相互作用

观察补中益气丸对糖尿病大鼠胃组织MuC1、COX-1、COX-2、cNOS、iNOS不同病程表达变化及其相互作用的影响、大鼠随机分为正常组。模型组和中药组,采用STZ腹腔注射结合乙醇灌胃的方法建立糖尿病大鼠胃黏膜损伤模型．检测胃组织NO、PGE2、6-ketoPC-F1d、MuCl、COX-1、cOX2、cNOS和iNOs随病程的表达变化及其相互作用。结果显示,糖尿病大鼠出现胃黏膜损伤和胃肠功能紊乱,胃组织MUC1、COX2、iNOS发生显著变化．MUC1随病程进展逐渐降低,iNOs和COX-2表现为早期活性降低,晚期活性升高,PGE2、6-keto—PGF1d和NO随病程显著升高,相关分析发现．COX1与cNOS呈显著正相关,与iNOS呈著负相关。补中益气丸能调节MUC1、COX-2、iNOS的表达及其相互作用,阻止胃黏膜损伤。结果表明,STZ腹腔注射结合乙醇灌胃的方法可成功诱导糖尿病大鼠胃黏膜损伤模型,iNOS与COX2可能为相互协作和相互介导的关系,在糖尿病胃黏膜损伤方面起重要作用,补中益气丸通过升高MUC1、降低iNOS和COX-2的表达及其相互作用,阻止胃黏膜损伤和糖尿病的发展。     

Involvement of granulin in estrogen-induced neurogenesis in the adult rat hippocampus

Recent studies have demonstrated the presence of neurogenesis in the adult mammalian hippocampus, and it has been suggested that estrogen and various growth factors influence the processes of adult neurogenesis. The present study assessed cell proliferation in the dentate gyrus and the mRNA expression levels of granulin, insulin-like growth factor-I (IGF-I), and brain-derived neurotrophic factor (BDNF) in the hippocampus 4 h after treatment with estradiol benzoate (EB) in 3- and 12-month old ovariectomized rats. At 3 months of age, mRNA expression of granulin precursor and cell proliferation were increased by EB treatment, although the mRNA expressions of IGF-I and BDNF remained unchanged. At 12 months of age, however, neither mRNA expression of the three genes nor cell proliferation in the dentate gyrus were affected by EB treatment. In addition, 17beta-estradiol enhanced the proliferation of neural progenitor cells derived from hippocampal tissue of 3-month-old female rats in vitro; this was inhibited by neutralization of granulin with specific antibody. These results suggest that estrogen induces granulin gene expression in the hippocampus and that the product of this gene is involved in the mitogenic effects of estrogen in the dentate gyrus, although the responses to estrogen decline with age.     

Time-course changes of hippocalcin expression in the mouse hippocampus following pilocarpine-induced status epilepticus

Hippocalcin participates in the maintenance of neuronal calcium homeostasis. In the present study, we examined the time-course changes of neuronal degeneration and hippocalcin protein level in the mouse hippocampus following pilocarpine-induced status epilepticus (SE). Marked neuronal degeneration was observed in the hippocampus after SE in a time-dependent manner, although neuronal degeneration differed according to the hippocampal subregions. Almost no hippocalcin immunoreactivity was detected in the pyramidal neurons of the cornu ammonis 1 (CA1) region from 6 h after SE. However, many pyramidal neurons in the CA2 region showed hippocalcin immunoreactivity until 24 h after SE. In the CA3 region, only a few hippocalcin immunoreactive cells were observed at 12 h after SE, and almost no hippocalcin immunoreactivity was observed in the pyramidal neurons from 24 h after SE. Hippocalcin immunoreactivity in the polymorphic cells of the dentate gyrus was markedly decreased from 6 h after SE. In addition, hippocalcin protein level in the hippocampus began to decrease from 6 h after SE, and was significantly decreased at 24 h and 48 h after pilocarpine-induced SE. These results indicate that marked reduction of hippocalcin level may be closely related to neuronal degeneration in the hippocampus following pilocarpine-induced SE.     

Thymoquinone enhances the activities of enzymes related to energy metabolism in peripheral leukocytes of diabetic rats

The aim of this study was to examine the effect of glycemic control using thymoquinone (TQ) on energy metabolism related enzymes in leukocytes of streptozotocin (STZ)-induced diabetic rats. The treatment of both TQ and insulin commenced 4 weeks after induction of diabetes. Plasma glucose, cholesterol and triglycerides levels were significantly reduced after TQ treatment, whereas immunoreactive insulin (IRI) showed significant increase. The activities of malate dehydrogenase (MDH) in cytosolic and mitochondrial fractions of peripheral blood leukocytes were significantly higher in rats treated with TQ and insulin as compared to that in diabetic controls. On the other hand the activities of lactic dehydrogenase (LDH) showed no significant changes between groups. ML ratio (cytosolic MDH/LDH specific activity ratio) was restored to those in the control rats. The results of this study demonstrate that TQ significantly increased insulin level and the activities of cytosolic and mitochondrial MDH in leukocytes of STZ-diabetic rats.     

Alteration of the gene and protein levels of insulin-like growth factors in streptozotocin-induced diabetic male rats

Insulin-like growth factor (IGFs: IGF-I and IGF-II) systems have been reported to be associated with the onset of diabetic mellitus. Therefore, we investigated the effect of diabetes on regulation of the IGF system in the liver, kidneys and heart, which are important organs in the pathogenesis of diabetes. The experimental groups were subdivided into three groups: 1) controls, 2) streptozotocin (STZ)-induced untreated diabetic group, and 3) an insulin-treated group (plus diabetic rats). In the present study, starting on the second day after STZ treatment, the diabetic group exhibited hyperglycemia, polyuria, and polydipsia, which are characteristic of diabetes melittus. Serum levels of IGF-I were decreased, but those of IGF-II were increased in the diabetic group compared with the controls. The expression levels of IGF-I and IGF-II protein in the livers of the diabetic group had a similar pattern to the serum. In addition, the expression levels of liver IGF-I mRNA and IGF-II mRNA were decreased in the diabetic groups. In the heart, IGF-I levels were decreased, but IGF-II levels were increased in the untreated diabetic groups, which was consistent with the expression levels of their mRNA. However, both the IGF-I and IGF-II levels in the kidneys were increased in the untreated diabetic groups, but the mRNA levels were decreased. Insulin treatment ameliorated the changes of IGF system in the serum, liver, kidneys, and heart. In conclusion, diabetes induced alteration of the IGF system tissue-specifically, and this was blocked by insulin treatment.     

Electroacupuncture at the Zusanli and Baihui acupoints ameliorates type-2 diabetes-induced reductions in proliferating cells and differentiated neuroblasts in the hippocampal dentate gyrus with increasing brain-derived neurotrophic factor levels

In the current study, we investigated whether electroacupuncture (EA) can inhibit pathological reductions in neurogenesis. Zucker diabetic fatty (ZDF) rats at 7 weeks of age were anesthetized with zoletil, and sham-acupuncture or EA at the Zusanli (ST36) and Baihui (GV20) acupoints was administered once a day for 5 weeks. In the ZDF group that received sham-EA (ZDF-Sham group), the blood glucose level was significantly increased together with age as compared to the control littermates [Zucker lean control (ZLC) rat]. In contrast, proliferating cells and differentiated neuroblasts were significantly decreased in the ZDF-Sham group compared to the ZLC group. Although EA treatment decreased blood glucose levels, this was not statistically significant when compared to blood glucose levels changes in the ZDF-Sham group. However, proliferating cells and differentiated neuroblasts were significantly increased with EA in ZDF rats as compared to those in the ZDF-Sham group. Brain-derived neurotrophic factor (BDNF) levels were significantly decreased in hippocampal homogenates of ZDF-Sham group compared to those in the ZLC group. The EA treatment significantly increased the BDNF levels compared to those in the ZDF-Sham group, and BDNF levels in this group were similar to those in the ZLC group. These results suggest that EA at ST36 and GV20 can ameliorate the reductions in proliferating cells and differentiated neuroblasts in the dentate gyrus induced by type-2 diabetes without significantly reducing blood glucose levels with increasing BDNF levels.     

前列腺素E2和F2α对LPS刺激后奶牛子宫内膜上皮细胞COX-1和COX-2表达的影响

试验旨在阐明前列腺素E₂（prostaglandin E₂,PGE₂）和F_2α（prostaglandin F_2α,PGF_2α）对体外培养的奶牛子宫内膜上皮细胞中环氧合酶-1（cyclooxygenase-1,COX-1））与环氧合酶-2（cyclooxygenase-2,COX-2）表达的影响。培养奶牛子宫内膜上皮原代细胞和传代细胞,第4代细胞以1×10⁶个/孔接种于6孔板,以10^-7mol/L PGE₂和PGF_2α分别预处理细胞24 h,以100 ng/mL细菌脂多糖（lipopolysaccharides,LPS）刺激细胞4、8和12 h后分别提取RNA和总蛋白质,采用实时荧光定量PCR与Western blotting等技术检测COX-1与COX-2 mRNA和蛋白质的表达量。结果表明,与对照组相比,COX-1 mRNA表达量在PGE₂单独作用4、8和12 h后显著上调（P<0.05）;COX-2 mRNA表达量在PGE₂单独作用4和12 h后显著上调（P<0.05）,PGE₂单独处理使COX-1、COX-2蛋白表达量均显著上调（P<0.05）。与对照组相比,LPS刺激8和12 h时COX-1 mRNA表达量显著下调（P<0.05）,LPS刺激后COX-1蛋白表达量无显著变化（P>0.05）;LPS刺激后4、8和12 h时COX-2 mRNA表达量显著上调（P<0.05）,LPS刺激后COX-2蛋白表达量显著上调（P<0.05）。与LPS单独处理组相比,LPS+PGE₂处理组在8和12 h时COX-1和COX-2 mRNA表达量均显著上调（P<0.05）,同时COX-1和COX-2蛋白表达量也显著上调（P<0.05）。PGF_2α在LPS未刺激和刺激后对COX-1和COX-2 mRNA的表达无显著影响（P>0.05）,仅在PGF_2α单独处理8和12 h后COX-1 mRNA表达量上调（P<0.05）。两种激素联合处理与各自单独处理及LPS单独刺激相比,对COX-1和COX-2 mRNA表达具有一定的协同诱导作用。     

Digestive enzyme activities of pancreas and intestinal digesta in streptozotocin-induced diabetic piglets

Six (Landrace × Large White) × Duroc crossbred, castrated weanling piglets were used to evaluate the effect of a streptozotocin (STZ) injection to induce diabetes on the activities of digestive enzymes derived from the pancreas (lipase, amylase, trypsin and chymotrypsin) in the pancreas and intestinal digesta. Fasting plasma glucose after the administration of STZ was maintained at the level of 302–491 mg/dL during this experiment, compared with the level of 89–125 mg/dL in the control group, and they were defined as the STZ‐induced diabetic piglets for about 7 weeks. Although their bodyweight increased in proportion to a quadratic curve (P < 0.0001) during 49 days after the administration of STZ, the growth of the STZ‐induced diabetic piglets was slower compared with the control. The STZ‐injection did not affect the percentage of the pancreas in bodyweight. The administration of STZ in the piglets tended to accelerate the activity of lipase (P = 0.06) and depress the activity of amylase (P = 0.15) or chymotrypsin (P = 0.18), as units/kg bodyweight, in the pancreas. In the case of measurement as units/kg bodyweight, the activities of intestinal digesta in the STZ group showed a tendency to be higher than those in control group, irrespective of the sort of enzymes. In conclusion, STZ‐induced diabetic piglets have a moderate digestive ability and the administration of exogenous digestive enzymes is not necessary when they are used as a diabetic animal model.     

Ribosomal protein s3 immunoreactivity in the young, adult and aged gerbil hippocampus

Ribosomal protein S3 (rpS3) is well known to participate in DNA repair mechanisms. In the present study, we compared rpS3 immunoreactivity and its protein levels in the hippocampus among young, adult and aged gerbils. In the postnatal month (PM) 3 group as the young, rpS3 immunoreaction was observed in pyramidal and non-pyramidal cells of the hippocampus proper and in granule and polymorphic cells of the dentate gyrus. In the PM 12 group as adult and 24 group as the aged, rpS immunoreactivity in the hippocampus was decreased compared to the PM 3 group. Western blot analysis showed that rpS3 levels were decreased with time; lowest at PM 24. These results indicate that rpS3 immunoreactivity and protein levels were markedly decreased in the aged gerbil hippocampus.     

2型糖尿病合并肾性高血压模型的建立及评价

制备一种发病过程类似于人类2型糖尿病合并肾性高血压疾病的大鼠模型。大鼠高脂高糖膳食4周后,予快速腹腔注射链脲佐菌素(STZ)溶液28mg/kg,制作成2型糖尿病模型。2周后,连续3d均测得空腹血糖(FBG)≥7.8mmoL/L或随机血糖(RBG)≥16.7mmol/L,为2型糖尿病成模标准。待血糖稳定后,再用改良的"两肾一夹法"结扎肾动脉,造成一侧肾动脉狭窄,形成肾性高血压。2周后,连续3d均测得大鼠收缩压(SBP)≥140mmHg,同时FBG≥7.8mmol/L或RBG≥16.7mmol/L,确定为2型糖尿病合并肾性高血压模型制作成功。4周后,模型大鼠血糖、血压稳定。与空白对照组相比,复合模型组大鼠出现体重减轻、空腹血糖升高、糖化血红蛋白值升高(P0.01),血压升高(P0.01);与糖尿病组和假手术组相比,复合模型组大鼠血肌酐,尿素氮变化不明显(P0.05),但血压明显升高(P0.01);同时,彩超结果显示,复合模型组大鼠左侧肾脏、肾动脉直径均变小,血流速增快。大鼠高脂高糖膳食后,用低剂量链脲佐菌素(STZ)溶液腹腔注射,再用改良的"二肾一夹"法制备的2型糖尿病合并肾性高血压大鼠模型,在一定程度上较好地模拟出该疾病的发病特点,可为2型糖尿病合并肾性高血压后的临床及试验研究提供一个稳定、实用、有效的新模型。