Purpose To study changes of cell cycle of vascular endothelial cell in non-proliferative diabetic retinopathy. Methods Alloxan induced Wistar-rats were employed and immunohistochemistry,Western blotting methods were used. Results The vascular endothelial cells of retinas of 8～20 weeks diabetic rats were observe to be cyclinD1,cyclinD3,cyclinB1,p21 and p27 positive stained with light and electronmicroscopies.CyclinE immuno-stained vascular endothelial cells was observed occasionally.Meanwhile,the evidences of morphologic changes of the vascular en dothelial cells were proved:less plasma,thinner cell,more bubble organelles than those of controls.But,the ultra-structures of pericytes and other type of retinal cells did not change and they also immunostain negative.Komas blue and Western blotting methods also proved that the vascular endothelial cells of retina of 20th week diabetic rats expressed cyclinD1,cyclinB1,p21 and p27 protein. Conclusion Glucose induced retinal vascular endothelial cells of 8～20th weeks diabetic rats enter cell cycle and were arrested at G1/S restriction point.This study also suggested that retinal vascular endothelial cells may possess the ability to resist glucose damage and mechanism of selfstability during very early stage of diabetes. (Chin J Ocul Fundus Dis,2000,16:173-176)
Objective To observe the effect of intravitreal injection of mouse nerve growth factor (NGF) on interphotoreceptor retinoid-binding protein (IRBP) in the vitreous of diabetic rats at early stages. Methods Ninety-six male Sprague Dawley (SD) rats were divided into control group (group A, 24 rats) and experimental group (72 rats). The rats in experimental group were induced with streptozotocin injection for diabetic retinopathy model, and then randomly divided into positive control group (group B), normal saline group (group C) and NGF group (group D), 24 rats in each group. The rats in the group A and B were not intervened. The rats were received intravitreal injection with 4mu;l normal saline (group C) or 4 mu;l (0.5 mu;g/mu;l) NGF (group D). At 2, 4, 6 and 8 weeks after injection, IRBP levels were detected by enzymelinked immunosorbent assay (ELISA); hematoxylin-eosin (HE) staining and light microscope were used to observe the morphological changes of the retina; transmission electron microscope was used to observe the retinal ultrastructure.Results At 2 weeks after injection, there was no significant difference in IRBP expression between group A,B,C and D (F=2.833，P=0.052). At 4, 6, 8 weeks after injection, the differences of IRBP expression between group A, B, C and D were significant (F=22.252, 108.459, 105.726; P=0.000). At different time points after injection, there was no significant difference in IRBP expression of group A (F=1.462, P=0.241), but there were significant differences in IRBP expression of group B, C and D (F=150.98, 63.519, 64.604; P=0.000). Light microscope found that the retinal structure was clear in group A and in group B, C, D at 2, 4 weeks after injection; the retinal thickness were thinner in group B, C, D at 8 weeks after injection. Transmission electron microscope displayed that the structure of rod outer segments was clear in group A and in group B, C, D at 2 weeks after injection; partly unclear structure of rod outer segments and slightly enlarged gap were observed in group B, C, D at 4, 8 weeks after injection. Conclusion Intravitreal injection with NGF can stabilize the IRBP expression in the vitreous of diabetic rats at early stages effectively.
ObjectiveTo explore the relationship of the level of inflammation and nutritional status with the occurrence and prognosis of refractory diabetic foot.MethodsA total of 70 patients with refractory diabetic foot between August 2015 and August 2017 were randomly selected as the observation group. Another 70 patients with diabetes mellitus (without foot ulcer) who visited the hospital in the same period were set as the control group. The observation group was subgrouped into the non-amputation group and the amputation group according to the follow-up endpoint events, and into the grade Ⅲ, Ⅳ, and Ⅴ groups according to Wagner classification method. The blood levels of inflammatory markers and nutritional markers between groups were compared.ResultsIn the observation group, vascular cell adhesion molecule-1 (VCAM-1), fibroblast growth factor 2 (FGF2), fibrinogen (FIB), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-18, lipoprotein phospholipase A2 (LP-PLA2), C-reactive protein (CRP) levels were significantly higher than those in the control group, and albumin (ALB), prealbumin (PA), and transferrin (TRF) levels were significantly lower than those in the control group, with statistically significant differences (P<0.01). The blood levels of FGF2, FIB, IL-6, IL-18, LP-PLA2, and CRP in the amputation group were significantly higher than those in the non-amputation group, and the levels of TRF, ALB, and PA were significantly lower than those in the non-amputation group (P<0.01). There were statistically significant differences in the levels of FGF2, FIB, IL-6, IL-18, LP-PLA2, CRP, TRF, ALB, and PA in patients with diabetic foot with different Wagner grades (P<0.05). The result of multiple logistic regression analysis showed that IL-6 [odds ratio (OR)=1.487, 95% confidence interval (CI) (1.023, 2.120), P<0.001], IL-18 [OR=1.274, 95%CI (1.052, 1.665), P<0.001], LP-PLA2 [OR=1.478, 95%CI (1.126, 1.789), P<0.001], and CRP [OR=2.085, 95%CI (1.574, 2.782), P<0.001] were independent risk factors for the occurrence of refractory diabetic foot, and TRF [OR=0.645, 95%CI (0.002, 0.898), P<0.001], ALB [OR=0.838, 95%CI (0.429, 0.923), P<0.001], and PA [OR=0.478, 95%CI (0.201, 0.984), P<0.001] were independent protective factors for the occurrence of refractory diabetic foot.ConclusionIn the clinical treatment of diabetic foot, we should pay attention to the monitoring of the level of inflammatory factors and nutritional status, and it is necessary to timely carry out anti-inflammatory treatment and appropriate nutritional support treatment.
Objective To observe whether theograde axial flow of retinal ganglion cells (RGC) in diabetic rats at the early stage was damaged. Methods Diabetic model was induced by streptozotocin in 6 adult male Sprague-Dawley (SD)rats. Fluorogold (FG) was injected to the superior colliculi 4 weeks later.Streched preparation of retina was made 12 and 72 hours after the injection, and was stained after photographed by fluorescent microscope. The proportion of RGC with different sizes labeled by FG was calculated. Other 6 normal adult male SD rats were in the control group. Results Twelve hours after injection with FG, there was no difference of the total number of RGC in experimental and control group, but the ratio of small RGC was lower in experimental group than that in the control group; 72 hours after injection with FG, The number of RGC, especially the small RGC, decreased obviously in experimental group compared with the control group. Conclusion The speed of the retrograde axial flow of RGC in diabetic rats at the early stage is affected, and the small RGC are damageable. (Chin J Ocul Fundus Dis, 2006, 22: 4-6)
Objective To investigate the effect of the damage and functional change of vascular endothelial cells (VEC) on diabetic retinopathy(DR). Methods Circulating endothelial cell (CEC) number and plasma endothelin(ET) level were measured in 18 normal control subjects and 55 patients with diabetes mellitus (DM) consisting of 20 cases of DM with out retinopathy,20 cases of DM with-background diabetic retinopathy and 15 cases of DM with proliferative diabetic retinopathy. Results CEC number and plasma ET level in DM were significantly higher than those in normal subjects(Plt;0.001)respectively.With the progression of DR,CEC number was significantly elevated and plasma ET level was gradually elevated.There was significant positive correlation between CEC number and plasma ET level (r=0.738,Plt;0.001,n=55). Conclusion VEC damage and elevated plasma ET level induced by VEC damage may play an important role in the development and progression of DR. (Chin J Ocul Fundus Dis,2000,16:166-168)
Objective To probe the relationship between the levels of two hormone,growth hormone (GH) and insulin-I like growth factor-I(IGF-I),and diabetic retinopathy (DR) in the patients with noninsulindependent diabetic mellitus (NIDDM)． Methods The direct radioimmunoassay was used to determine GH and IGF-I in the serum of 38 normal cotrols,61 NIDDM patients without DR,77 patients with the simple DR and 48 patients with the proliferative DR．Difference among these groups were analysed and compared by the methods of t test,F test and correlation analysis． Results The results showed that the levels of GH and IGF-I in the patients with diabetes [GH(1.659plusmn;1.509)ng/ml，IGF-I(118.7plusmn;52.0) ng/ml] were significantly higher than those in the normal controls [GH(0.619plusmn;0.351)ng/ml，IGF-I (63.6plusmn;30.6) ng/ml)] (P＜0.01),and those in the DR group were higher than those in the NIDDM without retinopathy group (P＜0.01),and levels of GH and IGF-I in the proliferative DR group [GH(2.953plusmn;1.648) ng/ml，IGF-I (159.2plusmn;47.5) ng/ml] ) were significantly higher than those in the simple DR group [GH(1.742plusmn;1.523) ng/ml，IGF-I (123.6plusmn;40.6) ng/ml] (P＜0.01)．SeveritY of DR was positively correlated with the levels of GH and IGF-I(P＜0.01)． Conclusion The results indicate that GH and IGF-I levels in the serum of patients with diabetes might be correlated with mechanisms and development of DR． (Chin J Ocul Fundus Dis,2000,16:30-31)
Objective To observe the relationship between retinal microglial activations and ganglion cell (RGC) damages in early-stage diabetic rats. Methods A total of 20 SpragueDawley（SD）rats were randomly divided into 4 groups (each with 5 rats): 1 month control group, 1 month diabetes group, 3 month control group, 3 month diabetes group. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ). The RGCs of all rats were retrograde labeled by carbocyanine dye DiI injected at the superior colliculi.Microglial cells and RGCs in retinal flat-mounts and sections were stained immunohistochemically and recorded under confocal microscope.Results The diabetic microglial cells were amoeboid and ovoid with fewer processes on retinal flat mounts. The density of microglial cells which phagocytosed DiI particles in the RGC layer significantly increased in the 3month diabetes group（P＜0.01）. The density of microglial cells in the RGC layer significantly increased in the 1- and 3- month diabetes group（P＜0.05）. However there were more microglial cells in the RGC layer in the 3- month diabetes group than the 1-month diabetes group（P＜0.0001）. Significant correlation was found between the amount of microglial cells and that of RGCs in the early-stage of diabetes. Conclusions Microglial cell activation has close relationship with the RGC damages in early-stage diabetic rats.
ObjectiveTo systematically evaluate the correlation between type-2 diabetes mellitus (T2DM) and T/C polymorphism in 190 locus ofβ3-adrenergic receptor (β3-AR) gene in Chinese population. MethodsThe following databases such as CNKI, VIP, CBM, PubMed, EMbase, the Cochrane Library (Issue 8, 2012) and WanFang Data were searched to collect case-control studies on the correlation between T2DM and T/C polymorphism in 190 locus of β3-AR gene. The retrieval time was from October 1980 to October 2013. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data and assessed the quality. Then the meta-analysis was conducted by using RevMan 5.0 and Stata 12.0 software, and the publication bias was analyzed by means of Egger's linear regression. ResultsA total of 11 studies involving 1 602 T2DM patients and 1 773 healthy volunteers were included. The results of meta-analyses showed that, for Chinese population, TC genotype in case group was more than that in control group[OR=1.19, 95%CI (1.01, 1.40), P=0.04]. CC+TC genotype in case group was more than that in control group[OR=1.23, 95%CI (1.05, 1.45), P=0.01]. Allele C in case group was more than that in control group[OR=1.24, 95%CI (1.08, 1.43), P=0.003]. ConclusionsThe allele C in 190 locus of β3-AR gene in Chinese population is significantly associated with T2DM. For the quantity and quality limitation of the included studies, this conclusion has to be further proved by more studies.
Objective To assess the effectiveness of bariatric surgery for obese type 2 diabetes mellitus (T2DM) in Mainland China. Methods Such databases as the Cochrane Central Register of Controlled Trials (Issue 2, 2012), MEDLINE (1990 to February 2012), EMbase (1990 to February 2012), CBM (1990 to February 2012), CNKI (1990 to February 2012), WanFang Data (1999 to February 2012) and VIP (1996 to February 2012) were searched, and the references of the included literature were also retrieved. The studies were screened according to the predefined inclusion and exclusion criteria, the data were extracted, the quality was evaluated, and then the meta-analysis was performed using RevMan 5.2 software. Results A total of 6 controlled before-and-after studies involving 100 patients were included. The overall quality of all literature was as low as grade C. The results of meta-analysis showed that the following indexes after operation obviously decreased than before: 1-month postoperative fasting plasma glucose (MD= –2.27, 95%CI ?4.12 to ?0.42, P=0.02), 6-month postoperative fasting plasma glucose (MD= ?2.73, 95%CI ?2.91 to 2.56, Plt;0.000 01), and 6-month postoperative glycated hemoglobin (SMD= ?1.97, 95%CI ?2.98 to ?0.96, P=0.000 1), and the differences were statistically significant. The sensitivity analysis indicated the results of meta-analysis were credible and stable, but the funnel-plot analysis displayed publication bias might exist in the included studies. Conclusion Current studies show that bariatric surgery is effective for obese T2DM patients in mainland China. However, due to small sample size and low methodological quality of the included studies, its effect has to be proved by high quality, large sample, and long follow-up studies.
Diabetes is characterised by hyperglycaemia resulted as the relative or absolute insulin deficiency which is closely related to islet beta cell failure. Apoptosis is the core mechanism of beta cell failure according to the studies on human islet. However, apoptosis can’t fully explain the loss of beta cell mass in the process of type 2 diabetes or the protective effect of early intervention. Recently, some other possible mechanisms of beta cell dysfunction have been proposed and dedifferentiation of beta cell draws extensive attention. Evidences of beta cell dedifferentiation in type 2 diabetes patients and animal models outlined and the transcription factors which determine beta cells of identity during this procedure are discussed in this review.