血清脂联素水平与2型糖尿病性视网膜病变的关系研究
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摘要
研究背景
脂联素是脂肪细胞特异分泌的蛋白质,在血液中通常以多聚体形式存在。按分子量不同,可分为低分子量脂联素、中分子量脂联素和高分子量脂联素。现有研究多集中在脂联素和肥胖、糖尿病、糖尿病大血管病变、癌症的关系等方面,且发现脂联素具有增强胰岛素敏感性、抗炎、抗动脉粥样硬化、抗癌等多种生物学活性。而对于脂联素与糖尿病性视网膜病变的关系研究较少,且存在很大争议,迄今为止共有三种观点:一种观点认为,随着糖尿病性视网膜病变的加重,血清脂联素水平降低,且显著低于无视网膜病变的2型糖尿病患者;第二种观点认为,随着糖尿病性视网膜病变的发展,血清脂联素水平没有变化,微血管病变不影响2型糖尿病患者的血清脂联素水平;第三种观点认为,随着糖尿病性视网膜病变的加重,血清脂联素水平逐渐增高。通过仔细分析,我们发现这些研究都存在着一定的缺陷,如没有控制其他变量对脂联素的影响、没有观察脂联素从健康人发展到糖尿病性视网膜病变各阶段的整个动态变化过程。
因此,从疾病预防控制的角度出发,通过合理分组、正确运用统计学方法和严格控制影响脂联素分泌的因素,研究2型糖尿病性视网膜病变患者的血清脂联素变化趋势,探索预测糖尿病性视网膜病变的总脂联素和高分子量脂联素水平的最佳截割点,以及分析2型糖尿病性视网膜病变发生的影响因素,对于揭示该病的发病机制和防治都具有较大的理论和实际意义。
研究目的
1.控制影响脂联素分泌的因素后,分析单纯糖尿病、非增殖性糖尿病性视网膜病变和增殖性糖尿病性视网膜病变患者的血清高分子量脂联素、总脂联素以及两者比值的水平。
2.摸索脂联素从健康人发展到糖尿病性视网膜病变各阶段的动态变化过程。
3.探讨血清高分子量脂联素和总脂联素对无视网膜病变的糖尿病和糖尿病性视网膜病变的预警价值;
4.分析2型糖尿病性视网膜病变发生的影响因素。
研究方法
根据设计方案,计算样本含量。从2007年10月至2008年12月期间前往山东施尔明眼科医院就诊和体检的对象中选取增殖性糖尿病性视网膜病变患者88例、非增殖性糖尿病性视网膜病变患者124例、无视网膜病变的糖尿病患者78例和“健康对照”84例。调查每位研究对象的性别、年龄、糖尿病病程、疾病史、家族史、服药史等一般情况;测量身高、体重和血压;实验室检测空腹血糖、胰岛素、甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、肿瘤坏死因子-α、肌酐、总脂联素和高分子量脂联素。
整理数据后,用SPSS16.0建立数据库并进行统计分析。运用协方差分析,控制其他变量对脂联素的影响后,观察比较四组间血清高分子量脂联素、总脂联素和两者比值的水平;运用ROC曲线分析血清总脂联素和高分子量脂联素对无视网膜病变的糖尿病和糖尿病性视网膜病变的预警价值;运用累加Logit模型分析2型糖尿病性视网膜病变发生的影响因素。
研究结果
1.2型糖尿病性视网膜病变患者的血清脂联素水平分析
单因素分析示,高血压病史、服药史、年龄、病程、空腹血糖、胰岛素、甘油三酯、总胆固醇、高密度脂蛋白胆固醇、肿瘤坏死因子-α、血肌酐、高分子量脂联素和总脂联素在四组间的差异有统计学意义(P＜0.05)。
协方差分析示,控制影响脂联素的因素后,四组间总脂联素水平差异有统计学意义(F=18.792,P＜0.01),健康对照组均高于其他三组(P＜0.01),增殖性糖尿病性视网膜病变组水平高于非增殖性糖尿病性视网膜病变组(P＜0.05)。四组间高分子量脂联素水平差异有统计学意义(F=14.025,P＜0.01),对照组均高于其他三组(P＜0.01)。四组间两者比值的差异没有统计学意义(P＞0.05)。
从健康对照到单纯糖尿病、糖尿病性视网膜病变各个阶段的过程中,血清总脂联素和高分子量脂联素都是先降低后升高的变化趋势。
2.脂联素对2型糖尿病性视网膜病变的预警价值
血清总脂联素预测单纯糖尿病发生的价值较大,其最佳截割点是4.796μg/ml,此处灵敏度是89.7%,特异度是81.0%。
血清总脂联素预测非增殖性糖尿病性视网膜病变的价值较大,其最佳截割点是3.406μg/ml,此处灵敏度是66.9%,特异度是72.2%。
没有找到预测增殖性糖尿病性视网膜病变发生的血清脂联素的最佳截割点,为避免发生较大的假阳性错误,故需要进一步研究。
3.2型糖尿病性视网膜病变发生的影响因素分析
在α=0.05水平上,有7个变量最终保留在累加Logit模型中,包括年龄、病程、服药史、高密度脂蛋白胆固醇、肿瘤坏死因子-α、高分子量脂联素和总脂联素。
结论
1.随着糖尿病和糖尿病性视网膜病变的发展,血清总脂联素和高分子量脂联素都是先降低后升高的变化趋势。在非增殖性糖尿病性视网膜病变阶段,两者的水平都较低,提示低脂联素水平可能参与非增殖性糖尿病性视网膜病变的发生。
2.血清总脂联素对单纯糖尿病和非增殖性糖尿病性视网膜病变的预测有一定的价值。
3.服药史、高水平的高密度脂蛋白胆固醇、高分子量脂联素和总脂联素水平对非增殖性糖尿病性视网膜病变具有保护作用;年龄大、糖尿病病程长、高水平的肿瘤坏死-α是非增殖性糖尿病性视网膜病变的危险因素。
BACKGROUND
Adiponectin is an adipocyte-specific secreted protein that usually exists as polymers in blood.By different molecular weight,it can be divided into three isforms, including the low-molecular-weight trimer,the middle-molecular-weight hexamer and the high-molecular-weight form composed of 12-18 molecules.Most researches focus on the relationship between adiponectin and obesity/diabetes/diabetic macrovascular diseases/cancer and indicate that adiponectin possesses many biological activities, such as enhanced insulin sensitivity,anti-inflammatory,anti-atherosclerosis, anti-cancer,etc.
So far,a few researches are done about the relationship between adiponectin and diabetic retinopathy.And three types of controversial opinions are held.The first opinion is that with the severity of diabetic retinopathy,the serum adiponectin concentration was lower and lower.And it was significantly lower than type 2 diabetic patients without retinopathy.The second view is that as diabetic retinopathy develops, serum adiponectin level does not change.This may indicate that microvascular lesions do not affect serum adiponectin level in type 2 diabetes.The third view is that as the diabetic retinopathy grows more severe,the serum adiponectin concentration increases gradually.By further analysis,we found some defects in these previous studies.For example,they neither control other variables impacting adiponectin nor observe the dynamic trend of adiponectin from healthy people to type 2 diabetic retinopathy patients.
Therefore,from the point of view of disease prevention and control,it has great theoretical and practical significance on revealing the pathogenesis of diabetic retinopathy by making clear that the variation of serum adiponectin in type 2 diabetic retinopathy controlled by diabetes and health group,exploring the cutting point of adiponectin preventing the diabetic retinopathy,and analyzing the influencing factors to type 2 diabetic retinopathy.It is also crucial to do researches through rational division,correct use of statistic methods and controlling factors influencing adiponectin.
OBJECTIVES
1.After controlling the factors influencing adiponectin,to analyze the serum level of the high-molecular-weigh adiponectin(HMW-adiponectin),total-adiponectin and their ratio in simple diabetic,non-proliferative diabetic retinopathy and proliferative diabetic retinopathy.
2.To observe the dynamic variation of adiponectin from healthy people to diabetic retinopathy patients.
3.To explore the waming value of serum level of HMW-adiponectin and total-adiponectin to simple diabetes,non-proliferatibe diabetic retinopathy and prolifeative diabetic retinopathy.
4.To investigate the impacting factors of type 2 diabetic retinopathy.
METHODS
In accordance with the proposed scheme,we calculated the size.In Shandong Shierming Eye Hospital,we chose 88 proliferative diabetic retinopathy patients,124 non-proliferative diabetic retinopathy patients,78 simple diabetes patients and 84 health control objects from October 2007 to December 2008.We investigated their gender,age,diabetes duration,disease history,family history,drug history and measured their height,weight,blood pressure,fasting plasma glucose(FPG),fasting insulin(FINS),triglyceride(TG),total cholesterol(T-C),high-density-lipoprotein cholesterol(HDL-C),low-density-lipoprotein cholesterol(LDL-C),tumor necrosis factor-α(TNF-α),creatinine,total-adiponectin and HMW-adiponectin.
We use SPSS 16.0 to set up the database for statistical analysis.By covariance analysis,after controlling the factors influncing the adiponectin,we observed the serum level of total-adiponectin and HMW-adiponectin within the four groups.By ROC curve analysis,we analyzed the warning value of the serum level total of totaladiponectin and HMW-adiponectin to simple diabetes and diabetic retinopathy.By Cumulative logit model,we analyzed the influencing factors of type 2 diabetic retinopathy.
RESULTS
1.The analysis of serum adiponectin level in patients with type 2 diabetic retinopathy.
Single factor analysis shows that hypertension history,drug history,age,duration, FPG,FINS,T-C,TG,HDL-C,TNF-α,creatinine,HMW-adiponectin and totaladiponectin have significant differences within four groups(P＜0.05).After controlling the factors influencing the adiponectin,covariance analysis shows that total-adiponectin has significant differences within four groups(F=18.792,P＜0.01). The total-adiponectin level of health control group is higher than the groups of simple diabetes,non-proliferative diabetic retinopathy and proliferative diabetic retinopathy (P＜0.01).The total-adiponectin level of proliferative diabetic retinopathy is higher than the group of non-proliferative diabetic retinopathy(P＜0.05).The serum level of HMW-adionectin has significant differences within four groups(F=14.025,P＜0.01). The HMW-adiponectin level of health control group is higher than the groups of simple diabetes,non-proliferative diabetic retinopathy and proliferative diabetic retinopathy(P＜0.01).The ratio of HMW-adiponectin/total-adiponectin has no differences(P＞0.05).
From health control,simple diabetes to each phrases of diabetic retinopathy,also with the severity of retinopathy,the dynamic variations of HMW and totaladiponectin grow down at the beginning and then grow up.
2.The warning value of adiponectin to type 2 diabetic retinopathy.
Total-adiponectin is better to forecast the occurance of simple diabetes.The optimal cut-point is 4.796μg/ml,sensitivity is 89.7%,specificity is 81.0%.To prevent the occurrence of non-proliferative diabetic retinopathy,the optimal cut-point of total-adiponectin is 3.406μg/ml,sensitivity is 66.9%,specificity is 72.2%.We do not find the optimal cut-point of adiponectin to proliferative diabetic retinopathy.To avoid the false-positive mistake,further study is needed.
3.The analysis of influencing factors of type 2 diabetic retinopathy.
Atα=0.05 level,there is finally seven variables retained in the cumulative logit model,including age,duration of disease,drug history,HDL-C,TNF-α,HMWadiponectin and total-adiponectin.
CONCLUSIONS
1.With the severity of diabetic retinopathy,the trends of HMW-adiponectin and total-adiponectin are all first down and then up.In the phase of non-proliferative diabetic retinopathy,both are the lowest.This indicates that lower level of serum adiponectin may participate the happening of non-proliferative diabetic retinopathy.
2.Serum total-adiponectin has greater value to forecast the simple diabetes and non-proliferative diabetic retinopathy.
3.Drug history,the high level of HDL-C,HMW-adiponectin and totaladiponectin have protective effects to the non-proliferative diabetic retinopathy.Older age,long duration of diabetes,high levels of TNF-αare risk factors of nonproliferative diabetic retinopathy.
脂联素是脂肪细胞特异分泌的蛋白质,在血液中通常以多聚体形式存在。按分子量不同,可分为低分子量脂联素、中分子量脂联素和高分子量脂联素。现有研究多集中在脂联素和肥胖、糖尿病、糖尿病大血管病变、癌症的关系等方面,且发现脂联素具有增强胰岛素敏感性、抗炎、抗动脉粥样硬化、抗癌等多种生物学活性。而对于脂联素与糖尿病性视网膜病变的关系研究较少,且存在很大争议,迄今为止共有三种观点:一种观点认为,随着糖尿病性视网膜病变的加重,血清脂联素水平降低,且显著低于无视网膜病变的2型糖尿病患者;第二种观点认为,随着糖尿病性视网膜病变的发展,血清脂联素水平没有变化,微血管病变不影响2型糖尿病患者的血清脂联素水平;第三种观点认为,随着糖尿病性视网膜病变的加重,血清脂联素水平逐渐增高。通过仔细分析,我们发现这些研究都存在着一定的缺陷,如没有控制其他变量对脂联素的影响、没有观察脂联素从健康人发展到糖尿病性视网膜病变各阶段的整个动态变化过程。
因此,从疾病预防控制的角度出发,通过合理分组、正确运用统计学方法和严格控制影响脂联素分泌的因素,研究2型糖尿病性视网膜病变患者的血清脂联素变化趋势,探索预测糖尿病性视网膜病变的总脂联素和高分子量脂联素水平的最佳截割点,以及分析2型糖尿病性视网膜病变发生的影响因素,对于揭示该病的发病机制和防治都具有较大的理论和实际意义。
研究目的
1.控制影响脂联素分泌的因素后,分析单纯糖尿病、非增殖性糖尿病性视网膜病变和增殖性糖尿病性视网膜病变患者的血清高分子量脂联素、总脂联素以及两者比值的水平。
2.摸索脂联素从健康人发展到糖尿病性视网膜病变各阶段的动态变化过程。
3.探讨血清高分子量脂联素和总脂联素对无视网膜病变的糖尿病和糖尿病性视网膜病变的预警价值;
4.分析2型糖尿病性视网膜病变发生的影响因素。
研究方法
根据设计方案,计算样本含量。从2007年10月至2008年12月期间前往山东施尔明眼科医院就诊和体检的对象中选取增殖性糖尿病性视网膜病变患者88例、非增殖性糖尿病性视网膜病变患者124例、无视网膜病变的糖尿病患者78例和“健康对照”84例。调查每位研究对象的性别、年龄、糖尿病病程、疾病史、家族史、服药史等一般情况;测量身高、体重和血压;实验室检测空腹血糖、胰岛素、甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、肿瘤坏死因子-α、肌酐、总脂联素和高分子量脂联素。
整理数据后,用SPSS16.0建立数据库并进行统计分析。运用协方差分析,控制其他变量对脂联素的影响后,观察比较四组间血清高分子量脂联素、总脂联素和两者比值的水平;运用ROC曲线分析血清总脂联素和高分子量脂联素对无视网膜病变的糖尿病和糖尿病性视网膜病变的预警价值;运用累加Logit模型分析2型糖尿病性视网膜病变发生的影响因素。
研究结果
1.2型糖尿病性视网膜病变患者的血清脂联素水平分析
单因素分析示,高血压病史、服药史、年龄、病程、空腹血糖、胰岛素、甘油三酯、总胆固醇、高密度脂蛋白胆固醇、肿瘤坏死因子-α、血肌酐、高分子量脂联素和总脂联素在四组间的差异有统计学意义(P＜0.05)。
协方差分析示,控制影响脂联素的因素后,四组间总脂联素水平差异有统计学意义(F=18.792,P＜0.01),健康对照组均高于其他三组(P＜0.01),增殖性糖尿病性视网膜病变组水平高于非增殖性糖尿病性视网膜病变组(P＜0.05)。四组间高分子量脂联素水平差异有统计学意义(F=14.025,P＜0.01),对照组均高于其他三组(P＜0.01)。四组间两者比值的差异没有统计学意义(P＞0.05)。
从健康对照到单纯糖尿病、糖尿病性视网膜病变各个阶段的过程中,血清总脂联素和高分子量脂联素都是先降低后升高的变化趋势。
2.脂联素对2型糖尿病性视网膜病变的预警价值
血清总脂联素预测单纯糖尿病发生的价值较大,其最佳截割点是4.796μg/ml,此处灵敏度是89.7%,特异度是81.0%。
血清总脂联素预测非增殖性糖尿病性视网膜病变的价值较大,其最佳截割点是3.406μg/ml,此处灵敏度是66.9%,特异度是72.2%。
没有找到预测增殖性糖尿病性视网膜病变发生的血清脂联素的最佳截割点,为避免发生较大的假阳性错误,故需要进一步研究。
3.2型糖尿病性视网膜病变发生的影响因素分析
在α=0.05水平上,有7个变量最终保留在累加Logit模型中,包括年龄、病程、服药史、高密度脂蛋白胆固醇、肿瘤坏死因子-α、高分子量脂联素和总脂联素。
结论
1.随着糖尿病和糖尿病性视网膜病变的发展,血清总脂联素和高分子量脂联素都是先降低后升高的变化趋势。在非增殖性糖尿病性视网膜病变阶段,两者的水平都较低,提示低脂联素水平可能参与非增殖性糖尿病性视网膜病变的发生。
2.血清总脂联素对单纯糖尿病和非增殖性糖尿病性视网膜病变的预测有一定的价值。
3.服药史、高水平的高密度脂蛋白胆固醇、高分子量脂联素和总脂联素水平对非增殖性糖尿病性视网膜病变具有保护作用;年龄大、糖尿病病程长、高水平的肿瘤坏死-α是非增殖性糖尿病性视网膜病变的危险因素。
BACKGROUND
Adiponectin is an adipocyte-specific secreted protein that usually exists as polymers in blood.By different molecular weight,it can be divided into three isforms, including the low-molecular-weight trimer,the middle-molecular-weight hexamer and the high-molecular-weight form composed of 12-18 molecules.Most researches focus on the relationship between adiponectin and obesity/diabetes/diabetic macrovascular diseases/cancer and indicate that adiponectin possesses many biological activities, such as enhanced insulin sensitivity,anti-inflammatory,anti-atherosclerosis, anti-cancer,etc.
So far,a few researches are done about the relationship between adiponectin and diabetic retinopathy.And three types of controversial opinions are held.The first opinion is that with the severity of diabetic retinopathy,the serum adiponectin concentration was lower and lower.And it was significantly lower than type 2 diabetic patients without retinopathy.The second view is that as diabetic retinopathy develops, serum adiponectin level does not change.This may indicate that microvascular lesions do not affect serum adiponectin level in type 2 diabetes.The third view is that as the diabetic retinopathy grows more severe,the serum adiponectin concentration increases gradually.By further analysis,we found some defects in these previous studies.For example,they neither control other variables impacting adiponectin nor observe the dynamic trend of adiponectin from healthy people to type 2 diabetic retinopathy patients.
Therefore,from the point of view of disease prevention and control,it has great theoretical and practical significance on revealing the pathogenesis of diabetic retinopathy by making clear that the variation of serum adiponectin in type 2 diabetic retinopathy controlled by diabetes and health group,exploring the cutting point of adiponectin preventing the diabetic retinopathy,and analyzing the influencing factors to type 2 diabetic retinopathy.It is also crucial to do researches through rational division,correct use of statistic methods and controlling factors influencing adiponectin.
OBJECTIVES
1.After controlling the factors influencing adiponectin,to analyze the serum level of the high-molecular-weigh adiponectin(HMW-adiponectin),total-adiponectin and their ratio in simple diabetic,non-proliferative diabetic retinopathy and proliferative diabetic retinopathy.
2.To observe the dynamic variation of adiponectin from healthy people to diabetic retinopathy patients.
3.To explore the waming value of serum level of HMW-adiponectin and total-adiponectin to simple diabetes,non-proliferatibe diabetic retinopathy and prolifeative diabetic retinopathy.
4.To investigate the impacting factors of type 2 diabetic retinopathy.
METHODS
In accordance with the proposed scheme,we calculated the size.In Shandong Shierming Eye Hospital,we chose 88 proliferative diabetic retinopathy patients,124 non-proliferative diabetic retinopathy patients,78 simple diabetes patients and 84 health control objects from October 2007 to December 2008.We investigated their gender,age,diabetes duration,disease history,family history,drug history and measured their height,weight,blood pressure,fasting plasma glucose(FPG),fasting insulin(FINS),triglyceride(TG),total cholesterol(T-C),high-density-lipoprotein cholesterol(HDL-C),low-density-lipoprotein cholesterol(LDL-C),tumor necrosis factor-α(TNF-α),creatinine,total-adiponectin and HMW-adiponectin.
We use SPSS 16.0 to set up the database for statistical analysis.By covariance analysis,after controlling the factors influncing the adiponectin,we observed the serum level of total-adiponectin and HMW-adiponectin within the four groups.By ROC curve analysis,we analyzed the warning value of the serum level total of totaladiponectin and HMW-adiponectin to simple diabetes and diabetic retinopathy.By Cumulative logit model,we analyzed the influencing factors of type 2 diabetic retinopathy.
RESULTS
1.The analysis of serum adiponectin level in patients with type 2 diabetic retinopathy.
Single factor analysis shows that hypertension history,drug history,age,duration, FPG,FINS,T-C,TG,HDL-C,TNF-α,creatinine,HMW-adiponectin and totaladiponectin have significant differences within four groups(P＜0.05).After controlling the factors influencing the adiponectin,covariance analysis shows that total-adiponectin has significant differences within four groups(F=18.792,P＜0.01). The total-adiponectin level of health control group is higher than the groups of simple diabetes,non-proliferative diabetic retinopathy and proliferative diabetic retinopathy (P＜0.01).The total-adiponectin level of proliferative diabetic retinopathy is higher than the group of non-proliferative diabetic retinopathy(P＜0.05).The serum level of HMW-adionectin has significant differences within four groups(F=14.025,P＜0.01). The HMW-adiponectin level of health control group is higher than the groups of simple diabetes,non-proliferative diabetic retinopathy and proliferative diabetic retinopathy(P＜0.01).The ratio of HMW-adiponectin/total-adiponectin has no differences(P＞0.05).
From health control,simple diabetes to each phrases of diabetic retinopathy,also with the severity of retinopathy,the dynamic variations of HMW and totaladiponectin grow down at the beginning and then grow up.
2.The warning value of adiponectin to type 2 diabetic retinopathy.
Total-adiponectin is better to forecast the occurance of simple diabetes.The optimal cut-point is 4.796μg/ml,sensitivity is 89.7%,specificity is 81.0%.To prevent the occurrence of non-proliferative diabetic retinopathy,the optimal cut-point of total-adiponectin is 3.406μg/ml,sensitivity is 66.9%,specificity is 72.2%.We do not find the optimal cut-point of adiponectin to proliferative diabetic retinopathy.To avoid the false-positive mistake,further study is needed.
3.The analysis of influencing factors of type 2 diabetic retinopathy.
Atα=0.05 level,there is finally seven variables retained in the cumulative logit model,including age,duration of disease,drug history,HDL-C,TNF-α,HMWadiponectin and total-adiponectin.
CONCLUSIONS
1.With the severity of diabetic retinopathy,the trends of HMW-adiponectin and total-adiponectin are all first down and then up.In the phase of non-proliferative diabetic retinopathy,both are the lowest.This indicates that lower level of serum adiponectin may participate the happening of non-proliferative diabetic retinopathy.
2.Serum total-adiponectin has greater value to forecast the simple diabetes and non-proliferative diabetic retinopathy.
3.Drug history,the high level of HDL-C,HMW-adiponectin and totaladiponectin have protective effects to the non-proliferative diabetic retinopathy.Older age,long duration of diabetes,high levels of TNF-αare risk factors of nonproliferative diabetic retinopathy.
引文
[1]刘国良.糖尿病诊断治疗的最新进展[J].中国实用内科杂志,2000,20(1):29-32.
[2]叶任高.内科学[M].第5版.北京:人民卫生出版社,2000,807.
[3]Liu DP,Molyneaux L,Chua E,et al.Retinopathy in a Chinese population with type 2 diabetes:factors affecting the presence of this complication at diagnosis of diabetes[J].Diabetes Res Clin Pract,2002,56(2):125-131.
[4]隋国良,葛在香,董砚虎.糖尿病视网膜病变的发病机制及其防治研究进展[J].国外医学内科学分册,2000,27(3):119-122.
[5]Arita Y,Kihara S,Ouchi N,et al.Paradoxical decrease of an adipose-specific protein,adiponectin,in obesity[J].Biochem Biophys Res Commun,1999,257(1):79-83.
[6]Scherer PE,Williams S,Fogliano M,et al.A novel serum protein similar to C1q,produced exclusively in adipocytes[J].J Biol Chem,1995,270(45):26746-26749.
[7]Brakenhielm E,Veitonmaki N,Cao R,et al.Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis[J].Proc Natl Acad Sci,2004,101(8):2476-2481.
[8]张合珍,李兴.脂联素与糖尿病视网膜病变[J].中国医学研究与临床,2006,4(12):45-48.
[9]Ouchi N,Kihara S,Arita Y.Adiponectin,an adipocyte-derived plasma protein,inhibits endothelial NF-κB signaling through a cAMP-dependent pathway[J].Circulation,2002,102(11):1296-1301.
[10]Ouchi N,Walsh K.Adiponectin as an anti-inflammatory factor[J].Clin Chim Acta,2007,380(1-2):24-30.
[11]Kadowaki T,Yamauchi T.Adiponectin and adiponectin Receptors[J].Endocr Rev,2005,26(3):439-451.
[12]Seino Y,Hirose H,Saito I,et al.High molecular weight multimer form of adiponectin as a useful marker to evaluate insulin resistance and metabolic syndrome in Japanese men[J].Metabolism,2007,56(11):1493-1499.
[13]Komaba H,Igaki N,Goto S,et al.Increased serum high-molecular-weight complex of adiponectin in type 2 diabetic patients with impaired renal function[J].Am J Nephrol,2006,26(5):476-482.
[14]Schober F,Neumeier M,Weigert J,et al.Low molecular weight adiponectin negatively correlates with the waist circumference and monocytic IL-6 release[J].Biochem Biophys Res Commun,2007,361(4):968-973.
[15]Yilmaz MI,Sonmez A,Acikel C,et al.Adiponectin may play a part in the pathogenesis of diabetic retinopathy[J].Eur J Endocrinol,2004,151(1):135-140.
[16]周贤会,郭开军.2型糖尿病视网膜病变患者血清脂联素水平的研究[J].检验医学与临床,2007,10(4):938-940.
[17]Hotta K,Funahashi T,Arita Y,et al.Plasma concentrations of a novel,adipose-specific protein,adiponectin,in type 2 diabetic patients[J].Arterioscler Thromb Vasc Biol,2000,20(6):1595-1599.
[18]Kato K,Osawa H,Ochi M,et al.Serum total and high molecular weight adiponectin levels are correlated with the severity of diabetic retinopathy and nephropathy[J].Clin Endocrinol,2008,68(3):442-449.
[19]Schraw T,Wang ZV,Halberg N,et al.Plasma adiponectin complexes have distinct biochemical characteristics[J].Endocrinology,2008,149(5):2270-2282.
[20]Kim KY,Kim JK,Han SH,et al.Adiponectin is a negative regulator of NK cell cytotoxicity[J].J Immunol,2006,176(10):5958-5964
[21]Dos Santos E,Benaitreau D,Dieudonne MN,et al.Adiponectin mediates an antiproliferative response in human MDA-MB 231 breast cancer cells[J].Oncol Rep,2008,20(4):971-977.
[22]王洁贞.医学统计学[M].研究生、医学七年制教材,山东大学公共卫生学院,142,219.
[23]Cantor SB,Sun CC,Tortolero-Luna G,et al.A comparison of C/B ratios from studies receiver operating characteristic curve analysis[J].J Clin Epidemiol,1999,52(9):885-892.
[24]Metz CE.ROC methodology in radiologic imaging[J].Invest Radiol,1986,21(9):720-733.
[25]邹莉玲,余小金,闵捷,等.ROC曲线在医学诊断中的应用与进展[J].东南大学学报(医学版),2003,22(1):67-70.
[26]金丕焕,主编.医用统计方法(第2版)[M].上海:复旦大学出版社,2003,430-431.
[27]Mitchell P,Smith W,Wang JJ,et al.Prevalence of diabetic retinopathy in an older community[J].Ophthalmol,1998,105(3):406-411.
[28]何守志,郭玉銮,李朝辉,等.首钢职工糖尿病视网膜病变流行病学调查[J]. 中华眼科杂志,1997,33(5):381-383.
[29]Nakano Y,Tobe T,Choi-Miura NH,et at.Isolation and characterization of GBP28,a novel gelatin-binding protein purified from human plasma[J].J Biochem,1996,120(4):803-812.
[30]Hu E,Liang P,Spiegelman BM.AdipoQ is a novel adipocyte-specific gene dysregulated in obesity[J].J Biol Chem,1996,271(18):10697-10703.
[31]Kishore U,Reid KB.C1q:structure,function,and receptors[J].Immuno-pharmacology,2000,49(1-2):159-170.
[32]Da Silva,Xavier GS,Leclerc L,et al.Role of AMP-activated protein kinase in the regulation by glucose of islet beta cell gene express[J].Proc Natl Acad Sci,2000,97:4023-4028
[33]Romeo G,Liu WH,Asnaghi V,et al.Activation of nuclear factor-kappaB induced by diabetes and high glucose regulates proapoptotic program in retinal pericytes[J].Diabetes,2002,51(7):2241-2248.
[34]Chen H,Montagnani M,Funahashi T,et al.Adiponectin stimulates production of nitric oxide in vascular endothelial cells[J].J Biol Chem,2003,278(45):45021-45026.
[35]Saito T,Saito O,Kawano T,et al.Elevation of serum adiponectin and CD146levels in diabetic nephropathy[J].Diabetes Res Clin Pract,2007,78(1):85-92.
[36]Lin J,Hu FB,Curhan G.Serum adiponectin and renal dysfunction in men with type 2 diabetes[J].Diabetes Care,2007,30(2):239-244.
[37]Fujita H,Morii T,Koshimura J,et al.Possible relationship between adiponectin and renal tubular injury in diabetic nephropathy[J].Endocr J,2006,53(6):745-752.
[38]朱巍,杨玉芝,李贤厚,等.2型糖尿病患者血清脂联素水平与糖尿病肾病的关系[J].放射免疫学杂志,2007,20(2):105-107.
[39]Koshimura J,Fujita H,Narita T,et al.Urinary adiponectin excretion is increased in patients with overt diabetic nephropathy[J].Biochem Biophys Res Commun,2004,316(1):165-169.
[40]Neumeier M,Sigruener A,Eggenhofer E,et al.High molecular weight adiponectin reduces apolipoprotein B and E release in human hepatocytes[J].Biochem Biophys Res Commun,2007,352(2):543-548.
[41]Yamauchi T,Kadowaki T.Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases[J]. Int J Obes (Lond), 2008, 32 Suppl 7: S13-8.
[42] Seino Y, Hirose H, Saito I, et al. High-molecular-weight adiponectin is a predictor of progression to metabolic syndrome: a population-based 6-year follow-up study in Japanese men[J]. Metabolism, 2009, 58(3): 355-360.
[43] Nakashima R, Kamei N, Yamane K, et al. Decreased total and high molecular weight adiponectin are independent risk factors for the development of type 2 diabetes in Japanese-Americans[J]. J Clin Endocrinol Metab, 2006, 91(10): 3873-3877.
[44] Broedl UC, Lebherz C, Lehrke M, et al. Low adiponectin levels are an independent predictor of mixed and non-calcified coronary atherosclerotic plaques [J]. PLoS ONE, 2009,4(3): e4733.
[45] Kobayashi H, Ouchi N, Kihara S, et al. Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin[J]. Circ Res, 2004, 94(4):e27-31.
[46] Schober F, Neumeier M, Weigert J, et al. Low molecular weight adiponectin negatively correlates with the waist circumference and monocytic IL-6 release[J].Biochem Biophys Res Commun, 2007, 361(4): 968-973.
[47] Tsao TS, Tomas E, Murrey HE, et al. Role of disulfide bonds in Acrp30/adiponectin structure and signaling specificity. Different oligomers activate different signal transduction pathways[J]. J Biol Chem, 2003, 278(50): 50810-50817.
[48] Abu El-Asrar AM, Desmet S, Meersschaert A, et al. Expression of the inducible isoform of nitric oxide synthase in the retinas of human subjects with diabetes mellitus[J]. Am J Ophthalmol, 2001,132(4): 551-556.
[49] Pajvani UB, Hawkins M, Combs TP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity [J]. J Biol Chem, 2004, 279: 12152-12162.
[50] Hara K, Horikoshi M, Yamauchi T, et al. Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome[J]. Diabetes Care, 2006,29(6):1357-1362.
[51] Aso Y, Yamamoto R, Wakabayashi S, et al. Comparison of serum high-molecular weight (HMW) adiponectin with total adiponectin concentrations in type 2 diabetic patients with coronary artery disease using a novel enzyme-linked immunosorbent assay to detect HMW adiponectin[J].Diabetes,2006,55(7):1954-1960.
[52]伍春荣,许樟荣,胡莲娜,等.2型糖尿病发生增生性糖尿病视网膜病变的危险因素[J].中华眼底病杂志,2003,19:338-340.
[53]刘罡,段俊国,张富大,等.2型糖尿病病程与视网膜病变的相关性[J].现代医药卫生,2004,20(2):79-80.
[54]孙文涛,张小玲,高嵩.糖尿病性视网膜视网膜病变发生发展的相关因素[J].国际眼科杂志,2005,5(4):755-759.
[55]章结楼,叶山东.糖尿病视网膜病变的有关危险因素[J].临床荟萃,2007,22(24):1799-1801.
[56]Kondo T,Vicent D,Suzuma K,et al.Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization[J].J Clin Invest,2003,111(12):1835-1842.
[57]Vicent D,Ilany J,Kondo T,et al.The role of endothelial insulin signaling in the regulation of vascular tone and insulin resistance[J].J Clin Invest,2003,111(9):1373-1380.
[58]谢熹玮,赵平.血管内皮生长因子在糖尿病视网膜病变发病机制中的研究进展[J].国外医学眼科学分册,2004,4(28):103.
[59]Ohta Y,Nozawa H,Tanaka Y,et al.Increased vascular endothelial growth factor and vascular endothelial growth factor-c and decreased nm23 expression associated with microdissemination in the lymph nodes in stage I non-small cell lung cancer[J].J Thorac Cardiovasc Surg,2000,119(4 Pt 1):804-813.
[60]Hiram F,Yoshida M,Niwa Y,et al.Insulin enhances leukocyte-endothelial cell adhesion in the retinal microcirculation through surface expression of intercellular adhesion molecule-1[J].Microvasc Res,2005,69(3):135-141.
[61]Dell S,Poulaki V,Mitsiades N,et al.Intensive insulin therapy-induced vascular leakage and leukostasis in diabetes are decreased by anti-IGF[J].Invest Ophthalmol Vis Sci,2004,45:4111.
[62]关小康,杜琳,董宇.胰岛素对糖尿病性视网膜病变影响的研究进展[J].吉林医学,2007,28(4):442-444.
[63]Nathan DM,Lachin J,Cleary P,et al.Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus[J].N Engl J Med,2003,348 (23):2294-2303.
[64]Jain A,Sarraf D,Fong D.Preventing diabetic retinopathy through control of systemic factors[J].Curr Opin Ophthalmol,2003,14(6):389-394.
[65]Hotanmisigil GS,Shargill NS,Spiegelman BM.Adipose expression of tumor necrosis factor-alpha:director role in obesity-linked insulin resistance[J].Science,1993,259(5091):87-91.
[66]Uysal KT,Wiesbrock SM,Marino MW,et al.Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function[J].Nature,1997,389(6651):610-614.
[67]陈雨,朱晓华.糖尿病视网膜病变发病机制的研究进展[J].国际眼科杂志,2006,6(2):433-435.
[68]Krady JK,Basu A,Allen CM,et al.Minocycline reduces proinflammatory cytokine expression,microglial activation,and caspase-3 activation in a rodent model of diabetic retinopathy[J].Diabetes,2005,54(5):1559-1565.
[2]叶任高.内科学[M].第5版.北京:人民卫生出版社,2000,807.
[3]Liu DP,Molyneaux L,Chua E,et al.Retinopathy in a Chinese population with type 2 diabetes:factors affecting the presence of this complication at diagnosis of diabetes[J].Diabetes Res Clin Pract,2002,56(2):125-131.
[4]隋国良,葛在香,董砚虎.糖尿病视网膜病变的发病机制及其防治研究进展[J].国外医学内科学分册,2000,27(3):119-122.
[5]Arita Y,Kihara S,Ouchi N,et al.Paradoxical decrease of an adipose-specific protein,adiponectin,in obesity[J].Biochem Biophys Res Commun,1999,257(1):79-83.
[6]Scherer PE,Williams S,Fogliano M,et al.A novel serum protein similar to C1q,produced exclusively in adipocytes[J].J Biol Chem,1995,270(45):26746-26749.
[7]Brakenhielm E,Veitonmaki N,Cao R,et al.Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis[J].Proc Natl Acad Sci,2004,101(8):2476-2481.
[8]张合珍,李兴.脂联素与糖尿病视网膜病变[J].中国医学研究与临床,2006,4(12):45-48.
[9]Ouchi N,Kihara S,Arita Y.Adiponectin,an adipocyte-derived plasma protein,inhibits endothelial NF-κB signaling through a cAMP-dependent pathway[J].Circulation,2002,102(11):1296-1301.
[10]Ouchi N,Walsh K.Adiponectin as an anti-inflammatory factor[J].Clin Chim Acta,2007,380(1-2):24-30.
[11]Kadowaki T,Yamauchi T.Adiponectin and adiponectin Receptors[J].Endocr Rev,2005,26(3):439-451.
[12]Seino Y,Hirose H,Saito I,et al.High molecular weight multimer form of adiponectin as a useful marker to evaluate insulin resistance and metabolic syndrome in Japanese men[J].Metabolism,2007,56(11):1493-1499.
[13]Komaba H,Igaki N,Goto S,et al.Increased serum high-molecular-weight complex of adiponectin in type 2 diabetic patients with impaired renal function[J].Am J Nephrol,2006,26(5):476-482.
[14]Schober F,Neumeier M,Weigert J,et al.Low molecular weight adiponectin negatively correlates with the waist circumference and monocytic IL-6 release[J].Biochem Biophys Res Commun,2007,361(4):968-973.
[15]Yilmaz MI,Sonmez A,Acikel C,et al.Adiponectin may play a part in the pathogenesis of diabetic retinopathy[J].Eur J Endocrinol,2004,151(1):135-140.
[16]周贤会,郭开军.2型糖尿病视网膜病变患者血清脂联素水平的研究[J].检验医学与临床,2007,10(4):938-940.
[17]Hotta K,Funahashi T,Arita Y,et al.Plasma concentrations of a novel,adipose-specific protein,adiponectin,in type 2 diabetic patients[J].Arterioscler Thromb Vasc Biol,2000,20(6):1595-1599.
[18]Kato K,Osawa H,Ochi M,et al.Serum total and high molecular weight adiponectin levels are correlated with the severity of diabetic retinopathy and nephropathy[J].Clin Endocrinol,2008,68(3):442-449.
[19]Schraw T,Wang ZV,Halberg N,et al.Plasma adiponectin complexes have distinct biochemical characteristics[J].Endocrinology,2008,149(5):2270-2282.
[20]Kim KY,Kim JK,Han SH,et al.Adiponectin is a negative regulator of NK cell cytotoxicity[J].J Immunol,2006,176(10):5958-5964
[21]Dos Santos E,Benaitreau D,Dieudonne MN,et al.Adiponectin mediates an antiproliferative response in human MDA-MB 231 breast cancer cells[J].Oncol Rep,2008,20(4):971-977.
[22]王洁贞.医学统计学[M].研究生、医学七年制教材,山东大学公共卫生学院,142,219.
[23]Cantor SB,Sun CC,Tortolero-Luna G,et al.A comparison of C/B ratios from studies receiver operating characteristic curve analysis[J].J Clin Epidemiol,1999,52(9):885-892.
[24]Metz CE.ROC methodology in radiologic imaging[J].Invest Radiol,1986,21(9):720-733.
[25]邹莉玲,余小金,闵捷,等.ROC曲线在医学诊断中的应用与进展[J].东南大学学报(医学版),2003,22(1):67-70.
[26]金丕焕,主编.医用统计方法(第2版)[M].上海:复旦大学出版社,2003,430-431.
[27]Mitchell P,Smith W,Wang JJ,et al.Prevalence of diabetic retinopathy in an older community[J].Ophthalmol,1998,105(3):406-411.
[28]何守志,郭玉銮,李朝辉,等.首钢职工糖尿病视网膜病变流行病学调查[J]. 中华眼科杂志,1997,33(5):381-383.
[29]Nakano Y,Tobe T,Choi-Miura NH,et at.Isolation and characterization of GBP28,a novel gelatin-binding protein purified from human plasma[J].J Biochem,1996,120(4):803-812.
[30]Hu E,Liang P,Spiegelman BM.AdipoQ is a novel adipocyte-specific gene dysregulated in obesity[J].J Biol Chem,1996,271(18):10697-10703.
[31]Kishore U,Reid KB.C1q:structure,function,and receptors[J].Immuno-pharmacology,2000,49(1-2):159-170.
[32]Da Silva,Xavier GS,Leclerc L,et al.Role of AMP-activated protein kinase in the regulation by glucose of islet beta cell gene express[J].Proc Natl Acad Sci,2000,97:4023-4028
[33]Romeo G,Liu WH,Asnaghi V,et al.Activation of nuclear factor-kappaB induced by diabetes and high glucose regulates proapoptotic program in retinal pericytes[J].Diabetes,2002,51(7):2241-2248.
[34]Chen H,Montagnani M,Funahashi T,et al.Adiponectin stimulates production of nitric oxide in vascular endothelial cells[J].J Biol Chem,2003,278(45):45021-45026.
[35]Saito T,Saito O,Kawano T,et al.Elevation of serum adiponectin and CD146levels in diabetic nephropathy[J].Diabetes Res Clin Pract,2007,78(1):85-92.
[36]Lin J,Hu FB,Curhan G.Serum adiponectin and renal dysfunction in men with type 2 diabetes[J].Diabetes Care,2007,30(2):239-244.
[37]Fujita H,Morii T,Koshimura J,et al.Possible relationship between adiponectin and renal tubular injury in diabetic nephropathy[J].Endocr J,2006,53(6):745-752.
[38]朱巍,杨玉芝,李贤厚,等.2型糖尿病患者血清脂联素水平与糖尿病肾病的关系[J].放射免疫学杂志,2007,20(2):105-107.
[39]Koshimura J,Fujita H,Narita T,et al.Urinary adiponectin excretion is increased in patients with overt diabetic nephropathy[J].Biochem Biophys Res Commun,2004,316(1):165-169.
[40]Neumeier M,Sigruener A,Eggenhofer E,et al.High molecular weight adiponectin reduces apolipoprotein B and E release in human hepatocytes[J].Biochem Biophys Res Commun,2007,352(2):543-548.
[41]Yamauchi T,Kadowaki T.Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases[J]. Int J Obes (Lond), 2008, 32 Suppl 7: S13-8.
[42] Seino Y, Hirose H, Saito I, et al. High-molecular-weight adiponectin is a predictor of progression to metabolic syndrome: a population-based 6-year follow-up study in Japanese men[J]. Metabolism, 2009, 58(3): 355-360.
[43] Nakashima R, Kamei N, Yamane K, et al. Decreased total and high molecular weight adiponectin are independent risk factors for the development of type 2 diabetes in Japanese-Americans[J]. J Clin Endocrinol Metab, 2006, 91(10): 3873-3877.
[44] Broedl UC, Lebherz C, Lehrke M, et al. Low adiponectin levels are an independent predictor of mixed and non-calcified coronary atherosclerotic plaques [J]. PLoS ONE, 2009,4(3): e4733.
[45] Kobayashi H, Ouchi N, Kihara S, et al. Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin[J]. Circ Res, 2004, 94(4):e27-31.
[46] Schober F, Neumeier M, Weigert J, et al. Low molecular weight adiponectin negatively correlates with the waist circumference and monocytic IL-6 release[J].Biochem Biophys Res Commun, 2007, 361(4): 968-973.
[47] Tsao TS, Tomas E, Murrey HE, et al. Role of disulfide bonds in Acrp30/adiponectin structure and signaling specificity. Different oligomers activate different signal transduction pathways[J]. J Biol Chem, 2003, 278(50): 50810-50817.
[48] Abu El-Asrar AM, Desmet S, Meersschaert A, et al. Expression of the inducible isoform of nitric oxide synthase in the retinas of human subjects with diabetes mellitus[J]. Am J Ophthalmol, 2001,132(4): 551-556.
[49] Pajvani UB, Hawkins M, Combs TP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity [J]. J Biol Chem, 2004, 279: 12152-12162.
[50] Hara K, Horikoshi M, Yamauchi T, et al. Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome[J]. Diabetes Care, 2006,29(6):1357-1362.
[51] Aso Y, Yamamoto R, Wakabayashi S, et al. Comparison of serum high-molecular weight (HMW) adiponectin with total adiponectin concentrations in type 2 diabetic patients with coronary artery disease using a novel enzyme-linked immunosorbent assay to detect HMW adiponectin[J].Diabetes,2006,55(7):1954-1960.
[52]伍春荣,许樟荣,胡莲娜,等.2型糖尿病发生增生性糖尿病视网膜病变的危险因素[J].中华眼底病杂志,2003,19:338-340.
[53]刘罡,段俊国,张富大,等.2型糖尿病病程与视网膜病变的相关性[J].现代医药卫生,2004,20(2):79-80.
[54]孙文涛,张小玲,高嵩.糖尿病性视网膜视网膜病变发生发展的相关因素[J].国际眼科杂志,2005,5(4):755-759.
[55]章结楼,叶山东.糖尿病视网膜病变的有关危险因素[J].临床荟萃,2007,22(24):1799-1801.
[56]Kondo T,Vicent D,Suzuma K,et al.Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization[J].J Clin Invest,2003,111(12):1835-1842.
[57]Vicent D,Ilany J,Kondo T,et al.The role of endothelial insulin signaling in the regulation of vascular tone and insulin resistance[J].J Clin Invest,2003,111(9):1373-1380.
[58]谢熹玮,赵平.血管内皮生长因子在糖尿病视网膜病变发病机制中的研究进展[J].国外医学眼科学分册,2004,4(28):103.
[59]Ohta Y,Nozawa H,Tanaka Y,et al.Increased vascular endothelial growth factor and vascular endothelial growth factor-c and decreased nm23 expression associated with microdissemination in the lymph nodes in stage I non-small cell lung cancer[J].J Thorac Cardiovasc Surg,2000,119(4 Pt 1):804-813.
[60]Hiram F,Yoshida M,Niwa Y,et al.Insulin enhances leukocyte-endothelial cell adhesion in the retinal microcirculation through surface expression of intercellular adhesion molecule-1[J].Microvasc Res,2005,69(3):135-141.
[61]Dell S,Poulaki V,Mitsiades N,et al.Intensive insulin therapy-induced vascular leakage and leukostasis in diabetes are decreased by anti-IGF[J].Invest Ophthalmol Vis Sci,2004,45:4111.
[62]关小康,杜琳,董宇.胰岛素对糖尿病性视网膜病变影响的研究进展[J].吉林医学,2007,28(4):442-444.
[63]Nathan DM,Lachin J,Cleary P,et al.Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus[J].N Engl J Med,2003,348 (23):2294-2303.
[64]Jain A,Sarraf D,Fong D.Preventing diabetic retinopathy through control of systemic factors[J].Curr Opin Ophthalmol,2003,14(6):389-394.
[65]Hotanmisigil GS,Shargill NS,Spiegelman BM.Adipose expression of tumor necrosis factor-alpha:director role in obesity-linked insulin resistance[J].Science,1993,259(5091):87-91.
[66]Uysal KT,Wiesbrock SM,Marino MW,et al.Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function[J].Nature,1997,389(6651):610-614.
[67]陈雨,朱晓华.糖尿病视网膜病变发病机制的研究进展[J].国际眼科杂志,2006,6(2):433-435.
[68]Krady JK,Basu A,Allen CM,et al.Minocycline reduces proinflammatory cytokine expression,microglial activation,and caspase-3 activation in a rodent model of diabetic retinopathy[J].Diabetes,2005,54(5):1559-1565.