Sulodexide protects against hyperglycemia-induced retinal vascular injury via suppressing NOX4/NLRP3 pathway

AIM To investigate the effect of sulodexide (SDX) on high glucose-induced damage in retinal microvascular endothelial cells. METHODS (1) High-fat diet combined with intraperitoneal injection of streptozocin were used to induce type 2 diabetes mellitus (DM) followed by injection of saline or SDX in C57BL/6J male mice. Retinal microvascular leakage and density, and the protein levels of NLRP3 inflammasome-related proteins, zonula occludens-1 (ZO-1) and NADPH oxidase 4 (NOX4) were measured. (2) Human retinal microvascular endothelial cells (HRMECs) were treated with normal glucose or high glucose with or without SDX, and were further transfected with siRNA to knock down NOX4, or infected by adenovirus to over-express NOX4. The protein levels of ZO-1, VE-cadherin (VE-Cad), NOX4 and NLRP3 inflammasome-related proteins as well as the level of reactive oxygen species (ROS) were detected. RESULTS Treatment with SDX increased the protein level of ZO-1, attenuated retinal leakage and NLRP3 inflammasome activation, and enhanced the density of microvasculature and the number of ganglion cells in diabetic retinas. The protein levels of ZO-1 and VE-Cad were decreased, while the levels of NOX4, NLRP3 inflammasome-related proteins and ROS generation were increased in high glucose-treated HRMECs. Silencing of NOX4 inhibited high glucose-induced increases in NLRP3 inflammasome and ROS generation, and decreases in the protein levels of ZO-1 and VE-Cad. Over-expression of NOX4 significantly increased the levels of NLRP3 inflammasome-related proteins and ROS generation in HRMECs, and reduced the protein levels of ZO-1 and VE-Cad. Treatment with SDX partly reversed NOX4 over-expression-induced changes. CONCLUSION SDX alleviates hyperglycemia-induced retinal microvascular endothelial injury via inhibiting NOX4/ROS/NLRP3 pathways.     

Bone morphological analyses in Spontaneously Diabetic Torii (SDT) fatty rats

The Spontaneously Diabetic Torii (SDT) fatty rat, a model for obese type 2 diabetes, shows bone quantitative abnormalities, namely low bone mineral density (BMD). The objective of this study was to evaluate bone morphological changes, in particular identifying the bone qualitative abnormalities, in the SDT fatty rat. Male SDT fatty rats showed increases in total trabecular area and trabecular number and decreases in trabecular thickness in cancellous bones of the proximal tibia, indicating trabecular miniaturization. The SDT fatty rat is useful for investigation of pathophysiological changes in bone quality in diabetic osteoporosis.     

富硒麦芽对链尿佐菌素诱发糖尿病大鼠糖脂代谢的影响

健康SD大鼠 72只随机分成 3组 ,正常对照组 (Ⅰ组 )和试验对照组 (Ⅱ组 )的饲料硒含量均为 0 1mg·kg-1;补富硒麦芽组 (Ⅲ组 )的饲料硒含量 0 3mg·kg-1。饲喂 5周后 ,Ⅱ、Ⅲ组用链尿佐菌素 (streptozotocin ,STZ)按每千克体重 6 0mg的剂量腹腔注射诱发糖尿病 ,Ⅰ组仅注射等剂量的缓冲液。继续饲喂 4周后观察各组大鼠抗氧化功能及糖、脂代谢变化。试验结果表明 ,补饲富硒麦芽能显著提高糖尿病大鼠胰岛素水平 ,降低血糖浓度 ;显著提高正常大鼠全血谷胱甘肽过氧化物酶 (GSH Px)活性 ,延缓糖尿病大鼠GSH Px和血浆超氧化物歧化酶活性下降趋势 ,降低血清胆固醇和甘油三酯浓度。提示补充适量的富硒麦芽 ,可增强STZ致糖尿病大鼠的抗氧化能力 ,降低血糖 ,降低脂质过氧化作用 ,改善糖、脂的代谢状态     

糖尿病性周围血管病患者血清中TM和EDHF的表达及意义

目的通过观察糖尿病性周围血管病患者血清中TM和EHDF的表达,探讨两者在该病中的意义.方法运用ELISA法检测32例糖尿病性周围血管病组、25例糖尿病组及20例正常组血清中TM与EDHF的表达,统计检测相关数据.结果糖尿病性周围血管病组及糖尿病组分别与正常组比较,两组血清中TM与EDHF明显高于正常组（P〈0.01）;糖尿病性周围血管病组与糖尿病组、正常组比较,血清中TM与EDHF显著高于后两组（P〈0.05）.相关性分析结果显示：TM与EDHF在糖尿病各组间血清中表达呈显著性正相关（P〈0.01）.结论 TM与EDHF参与糖尿病性周围血管病的发病过程,并且两者具有相关性,其可能在该病的发生、发展中起重要作用.     

Experimental transmission of encephalopathy and retinopathy induced by nodavirus to sea bream, Sparus aurata L., using different infection models

The transmission of viral encephalopathy and retinopathy (VER) was investigated in juvenile sea bream, Sparus aurata L. Two different infection routes [intraperitoneal (i.p.) and intramuscular injection (i.m.)] were tested at two different temperatures (20 and 26 °C) using sea bream of mean weight 0.7, 2 and 4 g, as well as an immersion challenge performed at 26 °C with sea bream of 0.7 g. Successful transmission of the disease was only achieved by i.m. injection. Mortalities of 100% occurred in sea bream of 0.7 g at day 15 post-infection and 47% in sea bream of both 2 and 4 g at day 30 post-infection in all the experimental infections at 26 °C. No mortalities were ever observed with infections at 20 °C. When mortalities were observed, the virus was detected by immunoperoxidase staining in the SSN-1 cell line inoculated with tissues from infected fish. Histological examination of both normal and infected fish showed a vacuolization in the bipolar and granular layers of the retina of the infected sea bream. This is the first experimentally induced transmission of VER in sea bream. Differences were observed at the time of disease onset depending on water temperature, the route of infection and the age of the juvenile fish.     

Protective immunity of sevenband grouper, Epinephelus septemfasciatus Thunberg, against experimental viral nervous necrosis

This paper describes the protective immune responses of sevenband grouper, Epinephelus septemfasciatus Thunberg, immunized with live piscine nodavirus, the causative agent of viral nervous necrosis (VNN), or the Escherichia coli – expressed recombinant coat protein. Nodavirus-neutralizing antibodies were detected at titres ranging from 1:158 to 1:1257 in serum of sevenband grouper which survived intramuscular injection with the virus, by a cell culture assay system. The virus-neutralizing ability of immune serum was also confirmed by injecting virus previously treated with serum into fish. This indicates establishment of acquired immunity in survivors and thus explains why survivors from natural infection are resistant to recurrence of the disease. Young sevenband grouper were immunized twice by intramuscular injections with the recombinant coat protein. Immunized fish produced neutralizing antibodies at high titres for at least 110 days and showed significantly lower mortalities in virus challenge tests. These results suggest the potential for vaccination against VNN in sevenband grouper, which is susceptible to piscine nodavirus at all life-stages.