Protective effect of rhIL-1β on pancreatic islets of alloxan-induced diabetic rats

AIM:To observe the protective effect of rhIL-1β on pancreatic islets of alloxan-induced diabetic rats. METHODS:Protection of rhIL-1β on pancreatic islets of alloxan-induced diabetic rats(n=5)was demonstrated with methods of immunohistochemistry and stereology.The concentration of serum glucose was measured by GOD method and that of serum insulin by RIA. RESULTS:The concentration of serum glucose increased but that of insulin decreased after administration of alloxan (150 mg/kg),and the volume density and numerical density of the islets were zero.In rhIL-1β pretreated rats, although the concentration of serum insulin decreased(from 11.9±3.0 mIU/L to 6.1±1.6 mIU/L,P<0.05),that of glucose was at normal level compared with the control group. As compared with alloxan group,the concentration of serum glucose in rhIL-1β pretreated rats decreased(from 19.4±8.9 mmol/L to 12.0±4.0 mmol/L,P<0.05)and the volume density increased(0/L to.1/L,P<0.05). CONCLUSION:rhIL-1β pretreatment may have protective effect on the islets of alloxan-induced diabetic rats.     

Effects of N-acetylcysteine on expression of transforming growth factor-β1 in diabetic nephropathy rats

Objective To investigate the effects of N-acetylcysteine (NAC) on the expression of transforming growth factor-β1 (TGF-β1) in renal cortex of diabetic nephropathy rats.Methods A rat model of DN was established.The rats were randomly divided into control group,DN group and NAC group.After 8 weeks treatment,urinary albumin excretion rate (UAER) was determined.The expression of TGF-β1 in renal cortex was detected by immunohistochemistry and RT-PCR analysis.Pathomorphological changes of renal cortex were observed.Results (1)The levels of UA ER were significantly higher in DN group and NAC group [(1268.3±297.5) μg/24 h and (315.9-±86.8) μg/24 h] than in control group [(31.2±8.9) μg/24 h,q-29.85,16.76,both P＜0.01].The groups of DN and NAC versus group of control showed the increased levels of activity of TGF-β1 in renal cortex [immune-histochemistry index of glomerular mesangial area:7.35±1.17 and 3.87 ± 0.71 vs.1.95±0.34,q= 10.75,5.82,both P＜0.01];immune-histochemistry index of renal tubulointerstitium [21.21± 3.78 and 10.67±1.86 vs.3.62±0.79,q=15.20,11.36,both P＜0.01];the expression of mRNA in renal cortex[0.72±0.06 and 0.45±0.05 vs.0.23±0.04,q=9.13,7.45,both P＜0.01].The pathomorphological changes were significant in DN group and NAC group.(2)The NAC group versus DN group showed a decreased levels of UAER (q=8.17,P＜0.01),activity of TGF-β1 in renal cortex [immune-histochemistry index of glomerular mesangial area:q= 4.97,P＜0.01]immune-histochemistry index of renal tubulointerstitium (q = 6.86,P ＜ 0.01 );the expression of mRNA in renal cortex (q= 3.69,P＜0.05) and showed improvement of pathomorphology in renal cortex.(3) There was a significantly positive correlation between expression quantity of TGF-β1 mRNA in renal cortex and UAER level in NAC group(r= 0.749,P＜0.05).Conclusions The protective effects of NAC on the kidney of DN rats may be partly related with inhibition on the expression of TGF-β1.     

Effects of N-acetylcysteine on expression of transforming growth factor-β1 in diabetic nephropathy rats

Objective To investigate the effects of N-acetylcysteine (NAC) on the expression of transforming growth factor-β1 (TGF-β1) in renal cortex of diabetic nephropathy rats.Methods A rat model of DN was established.The rats were randomly divided into control group,DN group and NAC group.After 8 weeks treatment,urinary albumin excretion rate (UAER) was determined.The expression of TGF-β1 in renal cortex was detected by immunohistochemistry and RT-PCR analysis.Pathomorphological changes of renal cortex were observed.Results (1)The levels of UA ER were significantly higher in DN group and NAC group [(1268.3±297.5) μg/24 h and (315.9-±86.8) μg/24 h] than in control group [(31.2±8.9) μg/24 h,q-29.85,16.76,both P＜0.01].The groups of DN and NAC versus group of control showed the increased levels of activity of TGF-β1 in renal cortex [immune-histochemistry index of glomerular mesangial area:7.35±1.17 and 3.87 ± 0.71 vs.1.95±0.34,q= 10.75,5.82,both P＜0.01];immune-histochemistry index of renal tubulointerstitium [21.21± 3.78 and 10.67±1.86 vs.3.62±0.79,q=15.20,11.36,both P＜0.01];the expression of mRNA in renal cortex[0.72±0.06 and 0.45±0.05 vs.0.23±0.04,q=9.13,7.45,both P＜0.01].The pathomorphological changes were significant in DN group and NAC group.(2)The NAC group versus DN group showed a decreased levels of UAER (q=8.17,P＜0.01),activity of TGF-β1 in renal cortex [immune-histochemistry index of glomerular mesangial area:q= 4.97,P＜0.01]immune-histochemistry index of renal tubulointerstitium (q = 6.86,P ＜ 0.01 );the expression of mRNA in renal cortex (q= 3.69,P＜0.05) and showed improvement of pathomorphology in renal cortex.(3) There was a significantly positive correlation between expression quantity of TGF-β1 mRNA in renal cortex and UAER level in NAC group(r= 0.749,P＜0.05).Conclusions The protective effects of NAC on the kidney of DN rats may be partly related with inhibition on the expression of TGF-β1.     

Effects of N-acetylcysteine on expression of transforming growth factor-β1 in diabetic nephropathy rats

Objective To investigate the effects of N-acetylcysteine (NAC) on the expression of transforming growth factor-β1 (TGF-β1) in renal cortex of diabetic nephropathy rats.Methods A rat model of DN was established.The rats were randomly divided into control group,DN group and NAC group.After 8 weeks treatment,urinary albumin excretion rate (UAER) was determined.The expression of TGF-β1 in renal cortex was detected by immunohistochemistry and RT-PCR analysis.Pathomorphological changes of renal cortex were observed.Results (1)The levels of UA ER were significantly higher in DN group and NAC group [(1268.3±297.5) μg/24 h and (315.9-±86.8) μg/24 h] than in control group [(31.2±8.9) μg/24 h,q-29.85,16.76,both P＜0.01].The groups of DN and NAC versus group of control showed the increased levels of activity of TGF-β1 in renal cortex [immune-histochemistry index of glomerular mesangial area:7.35±1.17 and 3.87 ± 0.71 vs.1.95±0.34,q= 10.75,5.82,both P＜0.01];immune-histochemistry index of renal tubulointerstitium [21.21± 3.78 and 10.67±1.86 vs.3.62±0.79,q=15.20,11.36,both P＜0.01];the expression of mRNA in renal cortex[0.72±0.06 and 0.45±0.05 vs.0.23±0.04,q=9.13,7.45,both P＜0.01].The pathomorphological changes were significant in DN group and NAC group.(2)The NAC group versus DN group showed a decreased levels of UAER (q=8.17,P＜0.01),activity of TGF-β1 in renal cortex [immune-histochemistry index of glomerular mesangial area:q= 4.97,P＜0.01]immune-histochemistry index of renal tubulointerstitium (q = 6.86,P ＜ 0.01 );the expression of mRNA in renal cortex (q= 3.69,P＜0.05) and showed improvement of pathomorphology in renal cortex.(3) There was a significantly positive correlation between expression quantity of TGF-β1 mRNA in renal cortex and UAER level in NAC group(r= 0.749,P＜0.05).Conclusions The protective effects of NAC on the kidney of DN rats may be partly related with inhibition on the expression of TGF-β1.     

Protective effects of tumor necrosis factor α antibody and ulinastatin on liver ischemic reperfusion in rats

AIM: To study the protective effects of tumor necrosis factor α (TNFα) antibody and ulinastatin on liver ischemic reperfusion in rats.METHODS: One hundred and twenty male SD rats were randomly divided into four groups: normal control group, ischemic group, TNFα antibody group and TNFα antibody + ulinastatin group. The animals were killed at 0, 3, 6, 9, 12 h after ischemia for 60 min and followed by reperfusion. Serum alanine aminotransferase (ALT), malondialdehyde (MDA) and liver histopathology were observed.RESULTS: After ischemic reperfusion, the serum ALT and MDA were remarkably increased, and the hepatic congestion was obvious. Treatment of TNFα antibody and ulinastatin could significantly decrease serum ALT and MDA levels, and relieve hepatic congestion.CONCLUSION: Ulinastatin and TNFα antibody can suppress the inflammatory reaction induced by hepatic ischemic reperfusion, and have protective effects on rat hepatic ischemic reperfusion injury.     

对暴发性1型糖尿病的探索仍在继续

暴发性1型糖尿病（FT1DM）是2000年Imagawa等[1]提出的1型糖尿病（T1DM）的新亚型,以胰岛β细胞呈超急性、完全不可逆性破坏、血糖急骤升高、糖尿病酮症酸中毒进展迅速、可缺乏糖尿病相关自身抗体为特征.FT1DM自首次被提出以来,引起了广泛关注,国内也相继有报道[2-5].目前有关FT1 DM的报道多集中在东亚人群,初步流行病学研究表明FT1DM占以酮症或糖尿病酮症酸中毒起病的T1DM患者的10％～20％[6].由于起病急骤、代谢紊乱极其严重,并可合并肝、肾、心脏、肌肉等多脏器的功能损害,如未及时诊断和治疗,常导致患者在短期内死亡.因此,作为内分泌代谢疾病中的急危重症,FT1DM应引起高度重视.     

Changes of gastric and intestinal blood flow, serum phospholipase A2 and interleukin-1β in rats with acute necrotizing pancreatitis

AIM: To explore the relationship between gastric and intestinal microcirculatory impairment and inflammatory mediators released in rats with acute necrotizing pancreatitis (ANP). METHODS: A total of 64 rats were randomized into control group and ANP group. ANP model was induced by injection of 5% sodium taurocholate under the pancreatic membrane. Radioactive biomicrosphere technique was used to measure the gastric and intestinal tissue blood flow at 2 and 12 h after the induction of ANP, meanwhile serum phospholipase A2 (PLA2) activities and interleukin-lβ levels were determined. Pathologic changes in pancreas, gastric and intestinal mucosae were studied. RESULTS: The gastric blood flow in ANP group (0.62&#177;0.06and 0.35&#177;0.05) mL/(min&#183;g) was significantly lower than that in control group (0.86&#177;0.11 and 0.85&#177;0.06) mL/(min&#183;g) (P&lt;0.01) at 2 and 12 h after induction of ANP. The intestinal blood flow in ANP group (0.80&#177;0.07 and 0.50&#177;0.06) mL/(min&#183;g) was significantly lower than that in control group (1.56&#177;0.18 and 1.61&#177;0.11) mL/(min&#183;g) (P&lt;0.01). Serum PLA2 activities (94.29&#177;9.96 and 103.71&#177;14.40) U/L and IL-Iβ levels (0.78&#177;0.13 and 0.83&#177;0.20) μg/Lin ANP group were higher than those in control group (65.27&#177;10.52 and 66.63&#177;9.81) U/L, (0.32&#177;0.06 and 0.33&#177;0.07)μg/L (P&lt;0.01). At 2 and 12 h after introduction of the model, typical pathologic changes were found in ANP. Compared with control group, the gastric and intestinal mucosal pathologic changes were aggravated significantly (P&lt;0.01) at 12 h after induction of ANP. Gastric and intestinal mucosal necrosis, multiple ulcer and hemorrhage occurred. CONCLUSION: Decrease of gastric and intestinal blood flow and increase of inflammatory mediators occur simultaneously early in ANP, both of them are importantpat hogenic factors for gastric and intestinal mucosal injury in ANP.     

Effects of Zuogui Wan on neurocyte apoptosis and down-regulation of TGF-β1 expression in nuclei of arcuate hypothalamus of monosodium glutamate -liver regeneration rats

AIM: To inquire into the effects and mechanism of Zuogui Wan (Pills for Kidney Yin) on neurocyte apoptosis in nuclei of arcuate hypothalamus (ARN) of monosodium glutamate (MSG)-Iiver regeneration rats, and the mechanism of liver regeneration by using optic microscope, electron microscope and in situ end labeling technology to adjust nerve-endocrine-immunity network.METHODS: Neurocyte apoptosis in ARN of the experiment rats was observed by using optic microscope, electron microscope and in situ end labeling technology. Expression of TGF-β1 in ARN was observed by using immunohistochemistry method.RESULTS: The expression of TGF-β1 in rats of model group was increased with the increase of ARN neurocyte apoptosis index (AI) (t = 8.3097, 12.9884, P&lt;0.01). As compared with the rats of model group, the expression of TGF-β1 in rats of Zuogui Wan treatment group was decreased with the significant decrease of ARN neurocyte apoptosis (t = 4.5624, 11.1420, P&lt;0.01).CONCLUSION: Brain neurocyte calcium ion overexertion and TGF-β1 protein participate in the adjustment and control of ARN neurocyte apoptosis in MSG-liver regeneration-rats. Zuogui Wan can prevent ARN neurocyte apoptosis of MSG-liver regeneration in rats by downregulating the expression of TGF-β1, and influence liver regeneration through adjusting nerve-endocrine-immunen etwork.     

Protective effect of rhIL-1β on pancreatic islets of alloxan-induced diabetic rats

AIM: To observe the protective effect of rhIL-1β on pancreatic islets of alloxan-induced diabetic rats.METHODS: Protection of rhIL-1β on pancreatic islets of alloxan-induced diabetic rats (n = 5) was demonstrated with methods of immunohistochemistry and stereology. The concentration of serum glucose was measured by GOD method and that of serum insulin by RIA.RESULTS: The concentration of serum glucose increased but that of insulin decreased after administration of alloxan(150 mg/kg), and the volume density and numerical density of the islets were zero. In rhIL-1β pretreated rats,although the concentration of serum insulin decreased (from11.9±3.0 mIU/L to 6.1±1.6 mIU/L, P＜0.05), that of glucose was at normal level compared with the control group.As compared with alloxan group, the concentration of serum glucose in rhIL-1β pretreated rats decreased (from19.4+8.9 mmol/L to 12.0±4.0 mmol/L, P＜0.05) and the volume density increased(0/L to. 1/L, P＜0.05).CONCLUSION: rhIL-1β pretreatment may have protective effect on the islets of alloxan-induced diabetic rats.     

Protective effect of brain-derived neurotrophic factor on pancreatic islets in obese diabetic mice

We have previously demonstrated that brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and energy expenditure in obese diabetic db/db mice. In the present study, the effect of BDNF treatment on pancreatic islets of db/db mice was examined, using vehicle-treated pair-fed db/db mice as controls. Brain-derived neurotrophic factor (10 mg/kg) or vehicle was subcutaneously administered to male db/db mice for 4 weeks. The food intake of vehicle-treated db/db mice was restricted and precisely synchronized with that of BDNF-treated db/db mice using a pellet pair-feeding apparatus because BDNF decreases food intake in hyperphagic mice. Repetitive administration of BDNF significantly lowered the blood glucose concentration compared with pair-fed vehicle-treated db/db mice. The pancreatic insulin and glucagon concentrations were measured in db/db mice to evaluate the effect of BDNF on the pancreas. Although the insulin concentration in the pancreas of pair-fed vehicle-treated db/db mice was lower than in nondiabetic control +m/+m mice, it was higher in BDNF-treated db/db mice than in vehicle-treated pair-fed db/db mice and comparable to the concentration in +m/+m mice. The glucagon concentration in the pancreas of vehicle-treated pair-fed db/db mice was higher than in +m/+m mice, and BDNF partially decreased the glucagon concentration in the pancreas of db/db mice compared with vehicle. Histologic analyses of pancreatic sections were performed to characterize the mechanism through which BDNF modulates the hormonal concentration in the pancreas of db/db mice. Although there were no significant differences in the number and total area of islets between the BDNF- and vehicle-treated groups, immunostaining with an anti-insulin antibody indicated that the islet beta-cell area in BDNF-treated db/db mice was larger than that in vehicle-treated pair-fed db/db mice. Furthermore, immunostaining with an antiglucagon antibody indicated that BDNF normalized the delocalization of non-beta cells in islets of db/db mice. Electron microscopic images of beta cells indicated a decrease in secretory granules in vehicle-treated pair-fed db/db mice; this change was reversed in BDNF-treated db/db mice and reached a level comparable to that found in +m/+m mice. These findings suggest that BDNF prevents exhaustion of the pancreas in diabetic mice by maintaining the histologic cellular organization of beta cells and non-beta cells in pancreatic islets and restoring the level of insulin-secreting granules in beta cells.     

罗格列酮对糖尿病大鼠残存胰岛β细胞的保护作用

目的观察罗格列酮（RSG）对糖尿病大鼠残存胰岛β细胞功能的影响。方法SD大鼠48只随机分为3组,正常对照（NC）组8只,糖尿病对照（DM）组20只,罗格列酮干预（RSG）组20只。DM、RSG两组成模糖尿病大鼠,RSG组即以罗格列酮灌胃（5mg&#183;kg^-1&#183;d^-1）,此后1、2、4、7、10周时,分别测定各组的FBG和FIns,DM、RSG两组分别在每个时间点各处死动物4只。透射电镜观察胰岛β细胞超微病变,免疫组化法检测胰岛中胰岛素水平。结果（1）与DM组相比,RSG组血清胰岛素水平逐渐上升,血糖水平逐渐下降。（2）RSG组β细胞数量增加,分泌颗粒增多。（3）RSG组胰岛表达胰岛素水平逐渐增高,并明显大于DM组（P〈0.05）。结论罗格列酮对糖尿病大鼠残存胰岛β细胞具有一定的保护作用。     

Sequential morphological changes in pancreatic islets of spontaneously diabetic rats

This study describes the sequential morphological changes in pancreatic islets from 1-, 6-, and 18-month-old male eSS rats, as compared to aged-matched control animals. Spontaneous diabetes mellitus was confirmed in 6- and 18-month-old eSS rats after an oral glucose tolerance test. Light microscopic immunocytochemical and morphometric techniques were used to study islet-cell populations. The pancreas was normal, and the morphometric methods did not reveal significant changes in islets from 1-month-old rats. However, 6-month-old eSS animals showed disruption of islet architecture and fibrosis in the stroma. The volume density (Vvi) of endocrine tissue and the Vvi and percentage of B cells were increased, whereas the Vvi of exocrine tissue and the Vvi and percentage of A cells were diminished. Eighteen-month-old eSS rats also exhibited conspicuous islet lesions. Nevertheless, the Vvi of endocrine tissue and the Vvi and percentage of B cells were diminished, while the Vvi of exocrine tissue and the Vvi and percentage of D cells were increased. Our results provide further quantitative evidence for the sequential morphological events occurring in the pancreatic islets of a useful animal model of diabetes mellitus.     

硝基酪氨酸在糖尿病大鼠胰岛中的表达及普罗布考的干预作用

目的观察硝基酪氨酸（NT）在糖尿病大鼠胰岛中的表达,以及普罗布考的干预对其表达和对胰岛β细胞的影响。方法大鼠高脂高糖饲料喂养4周后,腹腔注射链脲佐菌素30mg／kg复制2型糖尿病大鼠模型,普罗布考组（PB组）每天同时灌胃普罗布考500mg／kg,10周后测定空腹血糖（FPG）、空腹胰岛素（Fins）、总胆固醇（TC）、甘油三酯（TG）、丙二醛（MDA）、超氧化物歧化酶（SOD）,计算胰岛素敏感指数（ISI）,用免疫组化的方法观察NT在胰岛中的表达。结果糖尿病组（DM组）及PB组大鼠的FPG、TG、TC及MDA水平较正常对照组（NC组）明显增加（P〈0．01）,NT的平均光密度也明显高于NC组（P〈0．01）,但PB组上述指标的测定显著低于DM组（P〈0．01）;DM组和PB组大鼠的SOD水平、ISI明显低于NC组（P〈0．01）,PB组这些指标的测定显著高于DM组（P〈0．01）;NC组和PB组的Fins比较差异没有统计学意义,但都明显高于DM组（P〈0．01）。结论NT在胰岛的表达增强,普罗布考作为抗氧化剂,对于STZ引起的或糖尿病引起的氧化应激,均在一定程度上减轻其损伤,保护了胰岛功能。     

胎鼠胰腺干细胞体外对胰岛的保护作用观察

目的观察胎鼠胰腺干细胞体外对胰岛功能的保护作用。方法将孕16d的sD大鼠胎鼠胰腺干细胞分离、纯化、培养传代,免疫细胞化学法及流式细胞术鉴定;分离纯化sD大鼠胰岛,双硫腙鉴定后分为A组和B组,分别行单纯胰岛培养及胰岛与胰腺干细胞联合培养14d,期间观察胰岛形态变化、检测胰岛存活率及细胞凋亡率,ELISA法检测胰岛素分泌量、计算刺激指数。取两组培养7d后悬浮生长的胰岛移植入糖尿病大鼠左肾包膜下,术后每天尾静脉采血以快速血糖测试仪检测血糖。结果胎鼠胰腺干细胞培养传代3代后免疫细胞化学可见巢蛋白（Nestin）阳性细胞,流式细胞术测定其含量占74．1％;培养第7、14天时B组胰岛存活率显著高于A组（P均〈0．01）,培养第7天时B组胰岛细胞凋亡率显著低于A组（P〈0．05）;培养第7、14天时B组高糖刺激后胰岛素分泌量及刺激指数均显著高于A组（P均〈0．01）;B组移植后大鼠血糖第5天降至正常。结论胎鼠胰腺干细胞与胰岛联合培养可明显延长胰岛体外存活时间并使其保持良好的活性。     

Hypoglycaemic effect of Artemisia sphaerocephala Krasch seed polysaccharide in alloxan-induced diabetic rats

The purpose of this study was to examine the hypoglycaemic activity of a new polysaccharide extracted from seed polysaccharide (ASP) was administered orally for 4 weeks and the blood glucose changes were determined in fasted rats. Plasma insulin, cholesterol and triglycerides levels were also determined. The ASP at a dose of 200 mg/kg body weight (bw) produced a significant decrease in blood glucose levels in diabetic rats (P <0.01). In the other hand, the effect of the ASP on the plasma cholesterol were also significant in diabetic rats (P <0.05). Furthermore, there was a significant effect of ASP on plasma triglycerides in both normal and diabetic groups. In order to characterise the active principle(s), which could be responsible for the therapeutic effect, a preliminary phytochemical analysis of the ASP was performed. The monosaccharides of ASP were composed of L-Ara, D-Xyl, D-Lyx, D-Man, D-Glc, D-Gal. Their molar proportions were 1, 4.98, 1.69, 27.86, 3.76 and 13.92, respectively.     

槲皮素对糖尿病大鼠肾脏的保护作用

目的探讨槲皮素对糖尿病大鼠肾脏保护作用.方法对链脲佐菌素诱导糖尿病大鼠动物模型,给予槲皮素100mg*kg-1*d-1,治疗共8周.放免法测定尿白蛋白排泄率,测定内生肌酐清除率及肾小球蛋白激酶C活力.RT-PCR检测方法观察槲皮素对糖尿病大鼠肾脏皮质TGF-β1基因表达的影响,观察槲皮素对肾小球形态及病理改变.结果糖尿病大鼠存在肾小球高滤过,尿白蛋白排泄率、肾重/体重、肾小球细胞膜蛋白激酶C活力明显升高.肾脏皮质TGF-β1基因表达显著增加,肾小球肥大.给予槲皮素治疗2周及8周时,糖尿病大鼠肾小球滤过率、尿白蛋白排泄率、肾小球肥大均较糖尿病未治疗组显著降低,肾小球细胞膜蛋白激酶C活力及TGF-β1基因表达显著下降.肾脏病理改变不显著.结论槲皮素通过抑制糖尿病大鼠肾脏蛋白激酶C活力可以纠正糖尿病早期肾脏高滤过、高灌注,并同抑制肾脏皮质TGF-β1基因过度表达有关,抑制蛋白激酶C活性对防治糖尿病肾病尤为重要.     

解聚复肾宁对糖尿病大鼠肾脏的保护作用

目的 观察中药复方解聚复肾宁(JJFSN)对糖尿病 (DM)大鼠肾脏的保护作用.方法 建立链脲佐菌素(STZ)诱导的DM大鼠模型,将成模大鼠随机分成4组:模型组、JJFSN组、厄贝沙坦组、JJFSN+厄贝沙坦组,并设正常对照组.各组大鼠采用相应的干预措施处理12 w.常规方法检测各组大鼠尿白蛋白排泄率(UAER)等指标,免疫组化法检测肾血管内皮生长因子(VEGF)和骨形成蛋白7(BMP-7)表达,Western印迹检测肾组织血小板衍化生长因子B(PDGF-B)的表达,透射电镜观察肾脏超微结构.结果 模型组大鼠除肾BMP-7表达显著减少外,其余指标均显著增高,肾脏超微结构改变明显;JJFSN组、厄贝沙坦组和JJFSN+厄贝沙坦组除肾BMP-7显著高于模型组(P＜0.05)外,其余指标均显著低于模型组(P＜0.05),肾脏超微结构改变明显改善;JJFSN+厄贝沙坦组各项指标改善明显优于模型组、JJFSN组和厄贝沙坦组(P＜0.05),但未达到正常对照组水平.结论 JJFSN对DM大鼠肾脏有明显保护作用.     

血红素氧合酶-1对糖尿病大鼠视网膜神经节细胞的保护作用

目的探讨血红素氧合酶(HO)-1对糖尿病(DM)大鼠视网膜神经节细胞(RGC)保护作用及其机制。方法清洁级雄性SD大鼠24只中8只为对照组,余16只腹腔注射链脲佐菌素制作DM大鼠模型,将血糖浓度大于16.7 mmol/L的大鼠定为DM模型,随机分为DM组8只,另外8只腹腔注射HO-1特异性诱导剂正铁血红素为实验组,对照组及DM组腹腔注射等剂量生理盐水。12 w后,HE染色观察RGC密度,硫代巴比妥酸法检测丙二醛(MDA)含量,氮蓝四唑光化还原法测定超氧化物歧化酶(SOD)活性,免疫组化染色和Western印迹法检测视网膜HO-1、Caspase-3表达情况。结果与对照组相比,DM组RGC密度显著降低(P<0.01),而实验组无明显变化(P>0.05)。与对照组相比,DM组MDA含量明显升高、SOD活性明显降低(P<0.01),而实验组无明显变化(P>0.05)。HO-1在对照组仅微量表达于内核层,DM组阳性表达在节细胞层及内核层有所增加,而实验组阳性染色显著增加,特别是节细胞层。Caspase-3在对照组视网膜几乎无表达,而DM组阳性表达显著增多,主要分布于节细胞层及内核层,实验组与DM组相比阳性表达有所减弱。与对照组相比,HO-1在DM组及实验组蛋白表达量均增加(P<0.01),且实验组增加更明显(P<0.05);与对照组相比,Caspase-3在DM组蛋白表达显著增加(P<0.01),而实验组无明显变化。结论通过正铁血红素诱导HO-1在视网膜的高表达,下调了DM大鼠视网膜Caspase-3的表达,抑制了氧化应激,恢复了视网膜RGC密度;提示HO-1可能对DM大鼠RGC具有保护作用。