Objective To observe the expression of p53, bcl-2 genes, vascular endothelial cell growth factor（VEGF）, basic fibroblast growth factor（bFGF）, insulin-like growth factor-I （IGF-I）, and the receptors of these factors of retinal vascular endothelial cells (VECs) of 1- to 20-week diabetic rats, and the relationship between the expressions and cell cycle arrest.Methods Retinal sections of diabetic rats induced by alloxan were immunohistochemically stained and observed by light microscopy (LM) and electron microscopy (EM). Dot blotting and Western blotting were used to determine the expression of mRNA, proteins of p53 and bcl-2. Results Under LM, immunohistochemical positive expression of p53 and bcl-2 were found on the vessels of ganglion cell layer and inner nuclear layer of retinae of 8- to 20-week diabetic rats; under EM, these substances were observed depositing in VECs. The retinal VECs also expressed VEGF, bFGF, IGF-I and their receptors. There was no positive expression of other cell types in these retinae, all cell types of retinae in control group, or all cells of retinae of diabetic rats with the course of disease of 1 to 6 weeks. The result of dot blotting revealed that retinal tissue of 20-week diabetic rat expressed p53 and bcl-2 mRNA, and the result of Western blotting revealed that they also expressed p53 and bcl-2 proteins. But retinal tissues of control group did not. Positive expression of bax was not found in the retinae in control group or 1- to 20-week diabetic rats. Conclusion p53, bcl-2 may introduce cell cycle arrest of VECs of retinae in 8- to 20-week diabetic rats. High glucose might stimulate the expression of VEGF, bFGF, IGF-I and their receptors, and the growth factors may keep VECs surviving by self-secretion. (Chin J Ocul Fundus Dis，2003，19：29-33)
【摘要】 目的 探讨血浆内脏脂肪素(visfatin)与2型糖尿病的关系。方法 2007年7月—9月选取2型糖尿病患者和正常对照组各40例。根据体重指数再分为超重肥胖组和非超重肥胖组。检测visfatin水平、空腹血糖、空腹胰岛素、血脂、血压等,计算腰臀比、体重指数、稳态模型胰岛素抵抗指数homeostasis model assessment of insulin resistance,HOMAIR)及胰岛素分泌功能(HOMAβ)。结果 2型糖尿病组血浆visfatin水平显著低于正常对照组(Plt;0.05)。多元逐步相关分析表明,在肥胖的2型糖尿病个体中visfatin与高密度脂蛋白胆固醇、空腹血糖、体重指数呈负相关。二分类Logstic回归分析显示血浆visfatin及胰岛素抵抗指数与2型糖尿病的发生显著相关,回归方程式为Y=7.681+2.417 ln HOMAIR-2.549 visfatin。结论 visfatin的变化可能对2型糖尿病的发生、发展具有一定作用。
ObjectiveTo investigate the effect and mechanism of gastric bypass surgery (GBP) on fasting bloo-glucose (FBG) in type 2 diabetic rats. MethodsThe models of type 2 diabetic rats were induced by stretozotocin and 20 diabetic rats were randomly divided into two groups: diabetes-operation group (DO group, n=10) and diabetes-control group (DC group, n=10). Another twenty normal rats were randomly divided into two groups: normaloperation group (NO group, n=10) and normal-control group (NC group, n=10). The rats underwent GBP in DO group and NO group and sham operation in DC group and NC group. The FBG levels, serum dipeptidyl peptidase Ⅳ (DPPⅣ), and glucagon-like peptide-1 (GLP-1) concentrations of rats in each group were detected before operation and at 72 h, on 1 week, 4 weeks, and 8 weeks after operation. ResultsThe FBG levels of rats before operation were not significantly different between DO group and DC group or between NO group and NCgroup (Pgt;0.05). After operation, the FBG levels of rats in DO group gradually declined, reached the bottom on 4 weeks after operation and rose slightly on 8 weeks; The FBG levels of rats in DO group were lower after operation than before operation (Plt;0.05); After operation the FBG levels of rats in DO group were higher than that in NO group and NC group at the same time point (Plt;0.05); In DC group, the difference of FBG levels of rats at different time point was not statistically significant (Pgt;0.05); The inter-group and intra-group difference of FPG levels of rats for NO group and NC group was not statistically significant (Pgt;0.05). The concentrations of serum DPP-Ⅳ of rats before operation were not significantly different in each group (Pgt;0.05). After operation, the concentrations of serum DPP-Ⅳ of rats in DO group and NO group gradually decreased and markedly lower than that before operation, respectively (Plt;0.05). The concentrations of serum DPP-Ⅳ of rats after operation in DO group and NO group were significantly lower than that at the same time point in DC group and NC group, respectively (Plt;0.05); The intragroup difference of serum DPP-Ⅳ concentrations of rats for DC group and NC group was not statistically significant (Pgt;0.05). The concentrations of serum GLP-1 of rats before operation were not significantly different between DO group and DC group or between NO group and NC group (Pgt;0.05). After operation, the concentrations of serum GLP-1 of rats in DO group and NO group gradually increased, reached the top on 4 weeks after operation and declined slightly on 8 weeks; The concentrations of serum GLP-1 of rats in DO group and NO group were higher after operation than before operation (Plt;0.05);After operation, the concentrations of serum GLP-1 of rats in NO group were higher than that in NC group (Plt;0.05), but the concentrations of serum GLP-1 of rats at different time point in NO group were not different (Pgt;0.05). The intragroup difference of serum GLP-1 concentrations of rats for DC group and NC group was not statistically significant (Pgt;0.05). ConclusionsThere is obvious hypoglycemic effect of GBP on FBG levels of type 2 diabetic rats other than normal rats, in which high secretion of GLP-1 and low secretion of DPP-Ⅳ may be play an important role.
ObjectiveTo systematically evaluate the changes in placental protein expressions in gestational diabetes mellitus (GDM) and their correlations with maternal insulin resistance (IR). Methods PubMed, Cochrane Library, Scopus, Web of Science, Embase, China National Knowledge Infrastructure, VIP database, Wanfang Database and CBMdisc were searched for case-control studies published from January 2009 to November 2021, which reported the placental protein expressions in GDM and their correlations with IR. Two researchers independently reviewed the literature, extracted data and evaluated the literature quality. RevMan 5.4 software was used for meta-analysis, and descriptive analysis was performed on data that cannot be combined. ResultsA total of 19 studies were included, comprising 2 012 patients. The results of meta-analysis showed that: the expression level of retinol binding protein 4 (RBP4) [standard mean difference=2.11, 95% confidence interval (CI) (1.64, 2.58), P<0.000 01] and the positive rate of protein tyrosine phosphatase-1B (PTP1B) [relative risk (RR)=1.56, 95%CI (1.29, 1.88), P<0.000 01] were up-regulated, and the positive rate of insulin receptor substrate 1 (IRS-1) [RR=0.69, 95%CI (0.60, 0.78), P<0.000 01] was down-regulated. The protein expression levels of RBP4 (P<0.000 01) and PTP1B (P<0.000 01) were positively correlated with homeostasis model assessment of insulin resistance (HOMA-IR), while the protein expression levels of IRS-1 (P<0.000 01) and APN (P=0.002) were negatively correlated with HOMA-IR, and glucose transporter 4 (GLUT 4) was not correlated with HOMA-IR (P=0.79). Descriptive analysis found that the expression levels or positive rates of adipocytokines (leptin, resistin), oxidative stress markers (xanthione oxidase, malondialdehyde, 8-isoprostaglandin),inflammatory factors (tumor necrosis factor α, Toll-like receptor 4, Galectin-3, Galectin-2, migration inhibitory factor),fetuin-A, forkhead box transcription factor 1, forkhead box transcription factor 3a and estrogen receptor α in GDM placenta were up-regulated and all were positively correlated with HOMA-IR. The expression levels or positive rates of insulin signaling pathway proteins [phosphoinositide 3-kinase (PI3K), protein kinases B (AKT), phospho-protein kinases B (p-AKT), GLUT 4] were down-regulated, PI3K and AKT were negatively correlatedwith HOMA-IR, while p-Akt had no correlation with HOMA-IR. ConclusionsThe dysregulation of placental protein expressions may mediate maternal IR exacerbation, thus promote the occurrence and development of GDM and other pregnancy complications. The causal relationship and regulatory mechanism are still unclear, which need to be further studied.
Objective To investigate the early influences of laser photocoagulation on retinal function in diabetic retinopathy(DR)． Methods The multifocal electroretinograms (MERG) of 30 eyes with DR (phase Ⅲ～Ⅳ) were tested with visual evoked response image system IV b efore,and the 3rd day and the 7th day after laser photocoagulation． Results Three days after photocoagulation, the latency of N1 prolonged in the central macula 5deg; area and superionasal quadrant．Th e response densities of N1,P1 and N2 markedly reduced, and most significant changes occurred in the central macula 5deg; area and then in the central 10deg;area． There were also differences in the changes of the amplitude of N1 and P1 in diff erent quadrants ．The changes of visual acuity were positively related to the de crease of amplitudes of N1,P1 and N2 in the macula． Conclusion The reduction of response densities in MERG reveals functional damage in diabetic retina occurring early after photocoagulation．The functional damage in macula induced indirectly by photocoagulation may explain the reduction of visual acuity after panretinal photocoagulation in some degree． (Chin J Ocul Fundus Dis, 2001,17:181-183)
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)
ObjectiveTo evaluate the efficacy and safety of piolitazone combined with metformin for type 2 diabetes mellitus. MethodsThe Cochrane Library (Issue 9, 2015), PubMed, EMbase, CNKI, WanFang Data and VIP databases were searched up to September 2015 for randomized controlled trials (RCTs) about pioglitazone combined with metformin versus sulfonylurea combined with metformin for type 2 diabetes mellitus. Two reviewers independently screened literature, extracted date, and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.3 software. ResultsA total of 7 RCTs involving 3 005 patients were included. The results of metaanalysis showed that when the course of treatment was ≤24 weeks, no significant difference was found in the level of HbA1c between the piolitazone plus metformin group and the sulphonylurea plus metformin group (MD=-0.04, 95%CI -0.26 to 0.19, P=0.74), but the piolitazone plus metformin group had lower risk of hypoglycemia (RR=0.39, 95%CI 0.15 to 1.01, P=0.05); when the course of treatment >24 weeks, only one RCT was included, we didn't conduct pool analysis. ConclusionPiolitazone combined with metformin has similar effect to sulphonylurea combined with metformin in controlling blood sugar, but piolitazone combined with metformin has lower incidence of hypoglycemia. Due to limited quality and quantity of the included studies, the above conclusion need to be verified by more high quality studies.