α-SMA在代谢综合征大鼠模型肾脏的表达及其干预研究
摘要
研究目的:
1.构建代谢综合征大鼠模型。
2.探讨代谢综合征大鼠模型早期肾脏α-SMA的表达。
3.RAAS拮抗药物及降脂药物分别干预代谢综合征大鼠模型后早期肾脏α-SMA的表达变化。
研究方法:
1.动物模型的构建
选择3周龄SPF级雄性Wistar大鼠36只,随机分为正常饲料(含0.5%NaCl)喂养组(normal sodium, NS,n=12)、高盐高脂饲料(4%NaCl+49%Fat)喂养组(high sodium and fat, HSF,n=24)。饲养12周时,每组随机取6只处死(为NS-1组和HSF-1组),称体重,测量颈总动脉有创血压、血脂、血糖及血胰岛素浓度;根据稳态胰岛素抵抗指数(HOMA-IR index:fasting insulin X fasting glucose/22.5 [1])评价是否存在胰岛素抵抗,根据代谢综合征的诊断标准及统计学方法进行组间比较评价模型是否构建成功。
2.药物干预
NS组(n=6)继续以正常饲料喂养,为NS-2组。HSF组随机分为3组:一组继续单以高盐高脂饲料喂养(HSF-2组,n=6),其余动物在喂养高盐高脂饲料同时分别加入RAAS拮抗药替米沙坦(HSF+T,n=6,10mg/kg/d)及降脂药物辛伐他汀(HSF+S,n=6,10mg/kg/d)干预。至30周时结束实验,观察药物干预情况下体重、颈总动脉有创血压、血脂、血糖、血胰岛素浓度、计算稳态胰岛素抵抗指数。
3.代谢综合征大鼠肾组织形态学观察及免疫组化a-SMA表达建立以高盐高脂诱导的代谢综合征动物模型,饲养12周处死的大鼠及继续饲养18周到30周后的大鼠分离出肾脏组织,HE染色、Masson染色(20×10倍)使用Leica DM4000显微镜自带的显微成像系统在相同的条件下采集数码图片。免疫组化切片在Leica DM4000显微镜下按统一条件采集,每个组取3个连续切片,每个切片在10×20倍视野下随机取5个非重叠视野,避开切片边缘和组织破损区,拍照,用Image Pro Plus 6.0软件分析每张照片中阳性染色面积,选择常用的参数阳性面积(Area)的百分比代表a-SMA表达量。5个比值的平均值作为每个切片肾组织区域α-SMA的阳性率(%)。
研究结果:
1.体重变化
1.1高盐高脂致体重明显增加:实验12周,HSF-1组比NS-1组体重明显增加(326.45±6.84g比303.3±9.13g ,P<0.01);但实验30周时,NS-2组(434.73±10.19g),HSF-2组(458.83±12.85g),两组比较,P>0.05。结果提示高盐高脂饮食可在短期内增加体重。
1.2 RAAS拮抗药物对体重改变不明显:使用替米沙坦干预18周后测量体重,HSF+T组与NS-2及HSF-2组差异无统计学意义(P>0.05),结果提示:使用RAAS拮抗药物对体重无影响。
1.3辛伐他汀对体重改变不明显:使用辛伐他汀治疗18周后,HSF+S体重与NS-2及HSF-2组无差异(P>0.05)。结果提示:使用辛伐他汀干预对体重无影响。
2.颈总动脉有创血压
2.1高盐高脂导致收缩压升高:实验12周,HSF-1组(189.43±14.65mmHg)明显高于NS-1组(153.65±20.53mmHg ,P<0.01),同样,实验30周时HSF-2组(190.03±14.48mmHg)收缩压明显高于NS-2组(161.00±19.49mmHg,P<0.05)。结果提示长期高盐高脂饲料喂养正常Wistar大鼠可诱导形成高血压模型。
2.2替米沙坦有效降低收缩压:给予替米沙坦干预18周后检测收缩压发现,HSF+T组收缩压(161.95±15.62mmHg)较HSF-2组低(P<0.05);HSF+T组与NS-2组间无差异(P>0.05)。结果提示RAAS拮抗药能有效地降低由高盐高脂诱导的高血压。
2.3辛伐他汀对血压影响不明显:给予辛伐他汀干预18周后检测收缩压发现,HSF+S组收缩压(180.36±9.94mmHg)与HSF-2组比较无明显变化(P>0.05),均高于NS-2组(P<0.05)。
3.血脂改变
3.1实验12周,TG、TC及LDL在HSF-1组分别为0.97±0.54mmol/L、1.51±0.24mmol/L、0.90±0.23mmol/L,明显高于NS-1组(TG、TC、LDL分别为0.31±0.17mmol/L、0.88±0.12mmol/L、0.53±0.23mmol/L,P<0.05);两组HDL相近(0.83±0.17mmol/L对0.89±0.13mmol/L,P>0.05)。
3.2实验30周:
3.2.1 HSF-2组TG及LDL高于NS-2组(TG 2.96±0.56mmol/L对1.10±0.24mmol/L,LDL 2.60±0.51mmol/L对0.81±0.10mmol/L,P<0.05)。
3.2.2替米沙坦干预后血脂改变不明显:HSF+T组TG及LDL与HSF-2组比较无差异,P>0.05;HSF+T组高于NS-2组,P<0.05。
3.2.3辛伐他汀干预后TG及LDL降低:HSF+S组(TG 1.51±0.26mmol/L,LDL 1.17±0.26mmol/L)低于HSF-2组,P<0.05;两组TC及HDL差异无统计学意义,P>0.05。
4.血糖(FBG)、胰岛素(INS)及稳态胰岛素抵抗指数(HOMA-IR)的改变:实验12周,HSF-1组FBG和HOMA-IR明显高于NS-1组(8.01±1.52mmol/L对6.86±1.18mmol/L, 2.39±0.36对1.84±0.41,P<0.01)。INS水平两组比较差异无统计学意义,P>0.05。实验30周,HSF-2组HOMA-IR高于NS-2组,HSF-2组、HSF-T组及HSF-S组两两比较结果无统计学意义。结果表明:以高盐高脂饲料喂养正常Wistar大鼠可以导致胰岛素抵抗。
综上,高盐高脂能够诱导大鼠在12周后出现典型的代谢综合征改变:①体重增加:HSF-1组较NS-1组大鼠体重明显增加(BW:326.45±6.84g vs.303.3±9.13g,P<0.01);
②高血压:HSF-1组较NS-1组大鼠血压明显增高(BP:189.43±14.65 mmHg vs 153.65±20.53 mmHg,P<0.01);
③血脂异常:HSF-1组较NS-1组大鼠血脂明显增高(TC:1.51±0.24mmol/L vs. 0.88±0.12mmol/L, TG:0.97±0.54mmol/L vs. 0.31±0.17mmol/L, LDL-C: 0.90±0.23mmol/L vs. 0.53±0.23mmol/L,三者均P<0.05,但HDL-C:0.83±0.17mmol/L vs. 0.89±0.13mmol/L,P>0.05);
④胰岛素抵抗:HSF-1组大鼠胰岛素抵抗指数较NS-1组明显升高(HOMA-IR index:2.39±0.36 vs. 1.84±0.41,P<0.01)。
5.肾组织形态学检测
5.1 HE染色切片光镜下观察:NS-1、NS-2组无明显病理改变,表现为肾小球结构无改变,肾小管上皮细胞胞质丰富、小管管腔小、间质面积少。HSF-1组可见肾小球系膜轻度节段性增生、基底膜稍增厚,部分肾小管上皮细胞空泡变性、部分管腔扩张。HSF-2组病变较HSF-1组增加。HSF-T组、HSF-S组组织形态学类似HSF-2组。提示HSF组肾脏有轻度病理改变。
5.2 Masson染色光镜下观察:所见病理改变同HE染色,胶原纤维被染成兰色,细胞成红色,NS组Masson染色未见明显改变,肾小管基膜处见线状分布的兰染的胶原组织,HSF组胶原纤维较NS组稍增多。
6.肾脏组织免疫组化检测a-SMA表达:
6.1实验12周,HSF-1组肾脏a-SMA表达面积阳性百分比(0.03±0.005)稍高于NS-1组(0.015±0.008),但两组比较,P>0.05;提示12周时HSF组肾脏a-SMA表达增高。
6.2实验30周,HSF-2组(0.101±0.003)、HSF+T组(0.038±0.006)、HSF+S组(0.082±0.003)、NS-2组(0.02±0.004),四组比较,肾脏a-SMA表达面积阳性百分比存在差异(P<0.01),组间比较发现HSF-2组、HSF+S组肾脏a-SMA表达面积阳性百分比明显高于HSF+T组、NS-2组,而HSF-2组与HSF+S组,HSF+T组与NS-2组之间未发现明显差异,HSF+T组与HSF-2组比较(0.038±0.006 vs 0.101±0.003),P<0.05。提示30周时,HSF组肾脏a-SMA表达增高;替米沙坦治疗能有效减少a-SMA的表达;辛伐他汀对a-SMA表达影响不大。
结论:
1.高盐高脂饮食喂养12周大鼠出现代谢综合征,此时肾组织呈轻度肾损害,表现为肾小球系膜轻度节段性增生、基底膜稍增厚,部分肾小管上皮细胞空泡变性、部分管腔扩张;α-SMA在大鼠肾脏的表达增加,并随着饲养时间增加a-SMA的表达增高。
2.RAAS拮抗药物能有效降低代谢综合征大鼠肾脏α-SMA的表达,而降脂药物降低肾脏α-SMA的表达不明显。
[Aim] To build rat models with metabolic syndrome, to explore the expression ofα-SMA in kidney of Wistar rat with metabolic syndrome and intervention of RAAS antagonist and statins.
[Methods] 36 SPF Wistar male rats in 3 weeks were raised, randomly assigned to normal sodium group (NS,N=12) and high sodium-fat group (contained 4%NaCl+49%Fat,HSF,n=24). 6 rats in each group after 12 weeks’feeding was executed to check carotid artery pressure,glucose, fat, insulin in blood(NS-1 group and HSF-1 group).Then immunohistochemical staining ofα-SMA in kidney was performed. The other rats in HSF group was divided into three groups(HSF-2 with no intervention, HSF+T with oral RAAS antagonist and HSF+S with statins).The drug was administered with 10mg/kg/d. After 30 weeks’feeding, all other rats was executed and tested with carotid artery pressure,glucose, fat, insulin in blood andα-SMA in kidney.
[Results] Carotid artery pressure in HSF-1 was higher than in NS-1(189.43±14.65mmHg versus 153.65±20.53 mmHg,P<0.01) in 12 weeks,while Carotid artery pressure in HSF-2 was higher than NS-2(190.03±14.48mmHg versus 161.00±19.49mmHg,P<0.05)。RAAS antagonist helped decrease the pressure while statins couldn’t help.TG, TC and LDL in HSF-1 was 0.97±0.54mmol/L, 1.51±0.24mmol/L, 0.90±0.23mmol/L,compared with NS-1(0.31±0.17mmol/L, 0.88±0.12mmol/L, 0.53±0.23mmol/L,P<0.05). TG and LDL in HSF-2 were higher than those in NS-2(2.96±0.56mmol/L versus 1.10±0.24mmol/L, 2.60 ±0.51mmol/L versus 0.81±0.10mmol/L,P<0.05)。Statins helped ameliorate hyperlipemia,while RAAS antagonist couldn’t help. FBG and HOMA-IR in HSF-1 were higher than those in NS-1. (8.01±1.52mmol/L versus 6.86±1.18mmol/L, 2.39±0.36 versus 1.84±0.41,P<0.01). The levels of INS were similar in both groups(P>0.05).The positive rational of a-SMA expression in HSF-1 was small higher than in NS-1 (0.03±0.005versus 0.015±0.008, P > 0.05 ) .There were marked differences found in HSF-2,HSF+T,HSF+S and NS-2(P<0.01),while difference with a-SMA expression between HSF-2 and HSF+S was not detected. The expression of a-SMA in HSF+T and NS-2 was also similar。
[Conclusion] Rat with metabolic syndrome were successfully conducted with insulin resistence. A-SMA in kidney of rats with metabolic syndrome was higher expressed compared with normal sodium group. RAAS antagonist could be an effective intervention to prevent renal injuries with metabolic syndrome.
1.构建代谢综合征大鼠模型。
2.探讨代谢综合征大鼠模型早期肾脏α-SMA的表达。
3.RAAS拮抗药物及降脂药物分别干预代谢综合征大鼠模型后早期肾脏α-SMA的表达变化。
研究方法:
1.动物模型的构建
选择3周龄SPF级雄性Wistar大鼠36只,随机分为正常饲料(含0.5%NaCl)喂养组(normal sodium, NS,n=12)、高盐高脂饲料(4%NaCl+49%Fat)喂养组(high sodium and fat, HSF,n=24)。饲养12周时,每组随机取6只处死(为NS-1组和HSF-1组),称体重,测量颈总动脉有创血压、血脂、血糖及血胰岛素浓度;根据稳态胰岛素抵抗指数(HOMA-IR index:fasting insulin X fasting glucose/22.5 [1])评价是否存在胰岛素抵抗,根据代谢综合征的诊断标准及统计学方法进行组间比较评价模型是否构建成功。
2.药物干预
NS组(n=6)继续以正常饲料喂养,为NS-2组。HSF组随机分为3组:一组继续单以高盐高脂饲料喂养(HSF-2组,n=6),其余动物在喂养高盐高脂饲料同时分别加入RAAS拮抗药替米沙坦(HSF+T,n=6,10mg/kg/d)及降脂药物辛伐他汀(HSF+S,n=6,10mg/kg/d)干预。至30周时结束实验,观察药物干预情况下体重、颈总动脉有创血压、血脂、血糖、血胰岛素浓度、计算稳态胰岛素抵抗指数。
3.代谢综合征大鼠肾组织形态学观察及免疫组化a-SMA表达建立以高盐高脂诱导的代谢综合征动物模型,饲养12周处死的大鼠及继续饲养18周到30周后的大鼠分离出肾脏组织,HE染色、Masson染色(20×10倍)使用Leica DM4000显微镜自带的显微成像系统在相同的条件下采集数码图片。免疫组化切片在Leica DM4000显微镜下按统一条件采集,每个组取3个连续切片,每个切片在10×20倍视野下随机取5个非重叠视野,避开切片边缘和组织破损区,拍照,用Image Pro Plus 6.0软件分析每张照片中阳性染色面积,选择常用的参数阳性面积(Area)的百分比代表a-SMA表达量。5个比值的平均值作为每个切片肾组织区域α-SMA的阳性率(%)。
研究结果:
1.体重变化
1.1高盐高脂致体重明显增加:实验12周,HSF-1组比NS-1组体重明显增加(326.45±6.84g比303.3±9.13g ,P<0.01);但实验30周时,NS-2组(434.73±10.19g),HSF-2组(458.83±12.85g),两组比较,P>0.05。结果提示高盐高脂饮食可在短期内增加体重。
1.2 RAAS拮抗药物对体重改变不明显:使用替米沙坦干预18周后测量体重,HSF+T组与NS-2及HSF-2组差异无统计学意义(P>0.05),结果提示:使用RAAS拮抗药物对体重无影响。
1.3辛伐他汀对体重改变不明显:使用辛伐他汀治疗18周后,HSF+S体重与NS-2及HSF-2组无差异(P>0.05)。结果提示:使用辛伐他汀干预对体重无影响。
2.颈总动脉有创血压
2.1高盐高脂导致收缩压升高:实验12周,HSF-1组(189.43±14.65mmHg)明显高于NS-1组(153.65±20.53mmHg ,P<0.01),同样,实验30周时HSF-2组(190.03±14.48mmHg)收缩压明显高于NS-2组(161.00±19.49mmHg,P<0.05)。结果提示长期高盐高脂饲料喂养正常Wistar大鼠可诱导形成高血压模型。
2.2替米沙坦有效降低收缩压:给予替米沙坦干预18周后检测收缩压发现,HSF+T组收缩压(161.95±15.62mmHg)较HSF-2组低(P<0.05);HSF+T组与NS-2组间无差异(P>0.05)。结果提示RAAS拮抗药能有效地降低由高盐高脂诱导的高血压。
2.3辛伐他汀对血压影响不明显:给予辛伐他汀干预18周后检测收缩压发现,HSF+S组收缩压(180.36±9.94mmHg)与HSF-2组比较无明显变化(P>0.05),均高于NS-2组(P<0.05)。
3.血脂改变
3.1实验12周,TG、TC及LDL在HSF-1组分别为0.97±0.54mmol/L、1.51±0.24mmol/L、0.90±0.23mmol/L,明显高于NS-1组(TG、TC、LDL分别为0.31±0.17mmol/L、0.88±0.12mmol/L、0.53±0.23mmol/L,P<0.05);两组HDL相近(0.83±0.17mmol/L对0.89±0.13mmol/L,P>0.05)。
3.2实验30周:
3.2.1 HSF-2组TG及LDL高于NS-2组(TG 2.96±0.56mmol/L对1.10±0.24mmol/L,LDL 2.60±0.51mmol/L对0.81±0.10mmol/L,P<0.05)。
3.2.2替米沙坦干预后血脂改变不明显:HSF+T组TG及LDL与HSF-2组比较无差异,P>0.05;HSF+T组高于NS-2组,P<0.05。
3.2.3辛伐他汀干预后TG及LDL降低:HSF+S组(TG 1.51±0.26mmol/L,LDL 1.17±0.26mmol/L)低于HSF-2组,P<0.05;两组TC及HDL差异无统计学意义,P>0.05。
4.血糖(FBG)、胰岛素(INS)及稳态胰岛素抵抗指数(HOMA-IR)的改变:实验12周,HSF-1组FBG和HOMA-IR明显高于NS-1组(8.01±1.52mmol/L对6.86±1.18mmol/L, 2.39±0.36对1.84±0.41,P<0.01)。INS水平两组比较差异无统计学意义,P>0.05。实验30周,HSF-2组HOMA-IR高于NS-2组,HSF-2组、HSF-T组及HSF-S组两两比较结果无统计学意义。结果表明:以高盐高脂饲料喂养正常Wistar大鼠可以导致胰岛素抵抗。
综上,高盐高脂能够诱导大鼠在12周后出现典型的代谢综合征改变:①体重增加:HSF-1组较NS-1组大鼠体重明显增加(BW:326.45±6.84g vs.303.3±9.13g,P<0.01);
②高血压:HSF-1组较NS-1组大鼠血压明显增高(BP:189.43±14.65 mmHg vs 153.65±20.53 mmHg,P<0.01);
③血脂异常:HSF-1组较NS-1组大鼠血脂明显增高(TC:1.51±0.24mmol/L vs. 0.88±0.12mmol/L, TG:0.97±0.54mmol/L vs. 0.31±0.17mmol/L, LDL-C: 0.90±0.23mmol/L vs. 0.53±0.23mmol/L,三者均P<0.05,但HDL-C:0.83±0.17mmol/L vs. 0.89±0.13mmol/L,P>0.05);
④胰岛素抵抗:HSF-1组大鼠胰岛素抵抗指数较NS-1组明显升高(HOMA-IR index:2.39±0.36 vs. 1.84±0.41,P<0.01)。
5.肾组织形态学检测
5.1 HE染色切片光镜下观察:NS-1、NS-2组无明显病理改变,表现为肾小球结构无改变,肾小管上皮细胞胞质丰富、小管管腔小、间质面积少。HSF-1组可见肾小球系膜轻度节段性增生、基底膜稍增厚,部分肾小管上皮细胞空泡变性、部分管腔扩张。HSF-2组病变较HSF-1组增加。HSF-T组、HSF-S组组织形态学类似HSF-2组。提示HSF组肾脏有轻度病理改变。
5.2 Masson染色光镜下观察:所见病理改变同HE染色,胶原纤维被染成兰色,细胞成红色,NS组Masson染色未见明显改变,肾小管基膜处见线状分布的兰染的胶原组织,HSF组胶原纤维较NS组稍增多。
6.肾脏组织免疫组化检测a-SMA表达:
6.1实验12周,HSF-1组肾脏a-SMA表达面积阳性百分比(0.03±0.005)稍高于NS-1组(0.015±0.008),但两组比较,P>0.05;提示12周时HSF组肾脏a-SMA表达增高。
6.2实验30周,HSF-2组(0.101±0.003)、HSF+T组(0.038±0.006)、HSF+S组(0.082±0.003)、NS-2组(0.02±0.004),四组比较,肾脏a-SMA表达面积阳性百分比存在差异(P<0.01),组间比较发现HSF-2组、HSF+S组肾脏a-SMA表达面积阳性百分比明显高于HSF+T组、NS-2组,而HSF-2组与HSF+S组,HSF+T组与NS-2组之间未发现明显差异,HSF+T组与HSF-2组比较(0.038±0.006 vs 0.101±0.003),P<0.05。提示30周时,HSF组肾脏a-SMA表达增高;替米沙坦治疗能有效减少a-SMA的表达;辛伐他汀对a-SMA表达影响不大。
结论:
1.高盐高脂饮食喂养12周大鼠出现代谢综合征,此时肾组织呈轻度肾损害,表现为肾小球系膜轻度节段性增生、基底膜稍增厚,部分肾小管上皮细胞空泡变性、部分管腔扩张;α-SMA在大鼠肾脏的表达增加,并随着饲养时间增加a-SMA的表达增高。
2.RAAS拮抗药物能有效降低代谢综合征大鼠肾脏α-SMA的表达,而降脂药物降低肾脏α-SMA的表达不明显。
[Aim] To build rat models with metabolic syndrome, to explore the expression ofα-SMA in kidney of Wistar rat with metabolic syndrome and intervention of RAAS antagonist and statins.
[Methods] 36 SPF Wistar male rats in 3 weeks were raised, randomly assigned to normal sodium group (NS,N=12) and high sodium-fat group (contained 4%NaCl+49%Fat,HSF,n=24). 6 rats in each group after 12 weeks’feeding was executed to check carotid artery pressure,glucose, fat, insulin in blood(NS-1 group and HSF-1 group).Then immunohistochemical staining ofα-SMA in kidney was performed. The other rats in HSF group was divided into three groups(HSF-2 with no intervention, HSF+T with oral RAAS antagonist and HSF+S with statins).The drug was administered with 10mg/kg/d. After 30 weeks’feeding, all other rats was executed and tested with carotid artery pressure,glucose, fat, insulin in blood andα-SMA in kidney.
[Results] Carotid artery pressure in HSF-1 was higher than in NS-1(189.43±14.65mmHg versus 153.65±20.53 mmHg,P<0.01) in 12 weeks,while Carotid artery pressure in HSF-2 was higher than NS-2(190.03±14.48mmHg versus 161.00±19.49mmHg,P<0.05)。RAAS antagonist helped decrease the pressure while statins couldn’t help.TG, TC and LDL in HSF-1 was 0.97±0.54mmol/L, 1.51±0.24mmol/L, 0.90±0.23mmol/L,compared with NS-1(0.31±0.17mmol/L, 0.88±0.12mmol/L, 0.53±0.23mmol/L,P<0.05). TG and LDL in HSF-2 were higher than those in NS-2(2.96±0.56mmol/L versus 1.10±0.24mmol/L, 2.60 ±0.51mmol/L versus 0.81±0.10mmol/L,P<0.05)。Statins helped ameliorate hyperlipemia,while RAAS antagonist couldn’t help. FBG and HOMA-IR in HSF-1 were higher than those in NS-1. (8.01±1.52mmol/L versus 6.86±1.18mmol/L, 2.39±0.36 versus 1.84±0.41,P<0.01). The levels of INS were similar in both groups(P>0.05).The positive rational of a-SMA expression in HSF-1 was small higher than in NS-1 (0.03±0.005versus 0.015±0.008, P > 0.05 ) .There were marked differences found in HSF-2,HSF+T,HSF+S and NS-2(P<0.01),while difference with a-SMA expression between HSF-2 and HSF+S was not detected. The expression of a-SMA in HSF+T and NS-2 was also similar。
[Conclusion] Rat with metabolic syndrome were successfully conducted with insulin resistence. A-SMA in kidney of rats with metabolic syndrome was higher expressed compared with normal sodium group. RAAS antagonist could be an effective intervention to prevent renal injuries with metabolic syndrome.
引文
1. Dekker JM, Girman C, Rhodes T, Nijpels G, Stehouwer CDA, Bouter LM, Heine RJ. Metabolic syndrome and 10-year cardiovascular disease risk in the Hoorn Study. Circulation. 2005;112:666-73.
2. Eckel,RH,et al., The metabolic syndrome. Lancet. 2005,365:1415-1428.
3. McNeill AM, Rosamond WD, Girman CJ, Golden SH, Schmidt MI, East HE, Ballantyne CM, Heiss G. The metabolic syndrome and 11-year risk of incident cardiovascular disease in the atherosclerosis risk in communities study. Diabetes Care. 2005;28:385-390.
4. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287(3):356-9.
5. Tan CE, Ma S, Wai D, Chew SK, Tai ES.Can we apply the National Cholesterol Education Program Adult Treatment Panel definition of the metabolic syndrome to Asians? Diabetes Care. 2004;27(5):1182-6.
6. Palaniappan L, Carnethon M, Fortmann SP.Association between microalbuminuria and the metabolic syndrome: NHANES III.Am J Hypertens. 2003;16(11 Pt 1):952-8.
7. Praga M, Hernández E, Morales E, Campos AP, Valero MA, Martínez MA, León M.Clinical features and long-term outcome of obesity-associated focal segmental glomerulosclerosis.Nephrol Dial Transplant. 2001;16(9):1790-8.
8. Scopinaro N, Adami GF, Papadia FS, Camerini G, Carlini F, Briatore L, D'Alessandro G, Parodi C, Weiss A, Andraghetti G, Catalano M, Cordera R.The Effects of Biliopancreatic Diversion on Type 2 Diabetes Mellitus in Patients with Mild Obesity (BMI 30-35 kg/m(2)) and Simple Overweight (BMI 25-30 kg/m (2)): A Prospective Controlled Study. Obes Surg. 2011 May 4. [Epub ahead of print]
9. Ballantyne GH,Gumbs A,Modlin IM.Changes in insul in resistance following bariatricsurgery and the adipoinsular axis:role oftheadipocytokines, lep tin, adiponectin and resistin.ObesSurg. 2005;15(5):692-9.
10. EL-Atat FA,Stas SN,McFarlane SI,et a1.The relationship between hyperinsulinemia.hypertension andprogressive renal disease.J Am SocNephrol. 2004;15:2816-27.
11. MuléG, Cottone S, Nardi E, Andronico G, Cerasola G. Metabolic syndrome in subjects with essential hypertension: relationships with subclinical cardiovascular and renal damage. Minerva Cardioangiol. 2006;54(2):173-94.
12. Ginsberg HN.Insulin resistance and cardiovasculardisease.J C1in Invest.2000;106:453-8.
13. Lastra-Lastra G, Sowers JR, Restrepo-Erazo K, Manrique-Acevedo C, Lastra-González G. Role of aldosterone and angiotensin II in insulin resistance: an update. Clin Endocrinol (Oxf). 2009;71:1-6.
14. Qi, W., et al.,Transforming growth factor-beta1 differentially mediates fibronectin and inflammatory cytokine expression in kidney tubular cells. Am J Physiol Renal Physiol.2006 ;291(5):F1070-7.
15. Marcantoni C,Ma LJ,Fogo AB,et a1.Hypertensive nephrosclero-sis in AfricanAmericans versusCaucasians.KidneyInt.2002;62:172-80.
16. Kincaid—Smith P. Hypothesis: obesity and the insulin resistance syndrome playa major role in end-stage renal failure attributed to hypertension and labelled’hypertensive nephrosclerosis.J Hypertens. 2004;22:1051-5.
17. Fujita T. Aldosterone and CKD in metabolic syndrome.Curr Hypertens Rep.2008,10 :421-3.
18. Nagase M, Yoshida S, Shibata S, Nagase T, Gotoda T, Ando K, Fujita T.Enhanced aldosterone signaling in the early nephropathy of rats withmetabolic syndrome: possible contribution of fat-derived factors. J Am Soc Nephrol. 2006 Dec;17(12):3438-46
19. Chen, Z., et al. , Simvastatin reduces neointimal thickening in low-density lipoprotein receptor-deficient mice after experimental angioplasty without changing plasma lipids. Circulation. 2002;106(1): 20-3.
20. Rule AD, Semret MH, Amer H, Cornell LD, Taler SJ, Lieske JC, Melton LJ 3rd, Stegall MD, Textor SC, Kremers WK, Lerman LO. Association of kidney function and metabolic risk factors with density of glomeruli on renal biopsy samples from living donors.Mayo Clin Proc. 2011 Apr;86(4):282-90.
21. Iglesias P, Díez JJ. Adipose tissue in renal disease: clinical significance and prognostic implications. Nephrology Dialysis Transplantation. 2010;25(7):2066–2077.
22. Gilbert EL, Ryan MJ.High dietary fat promotes visceral obesity and impaired endothelial function in female mice with systemic lupus erythematosus. Gend Med. 2011;8(2):150-5.
23. Ritz E. Metabolic syndrome and kidney disease. Blood Purification. 2008;26(1):59–62.
24. Lee SH, Park SA, Ko SH, et al. Insulin resistance and inflammation may have an additional role in the link between cystatin C and cardiovascular disease in type 2 diabetes mellitus patients. Metabolism. 2010;59(2):241–246.
25. Zapolski T, Waciński P, Kondracki B, Rychta E, Buraczyńska MJ, Wysokiński A. Uric acid as a link between renal dysfunction and both pro-inflammatory and prothrombotic state in patients with metabolic syndrome and coronary artery disease. Kardiol Pol. 2011;69(4):319-26.
26. Savino A, Pelliccia P, Chiarelli F, Mohn A. Obesity-related renal injury in childhood. Hormone Research in Paediatrics.2010;73(5):303–311.
27. Basi S, Lewis JB. Microalbuminuria as a target to improve cardiovascular and renal outcomes. American Journal of Kidney Diseases. 2006;47(6):927–946.
28. Shlipak MG, Katz R, Sarnak MJ, et al. Cystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease. Annals of Internal Medicine. 2006;145(4):237–246.
29. Surendar J, Indulekha K, Aravindhan V, Ganesan A, Mohan V. Association of cystatin-C with metabolic syndrome in normal glucose-tolerant subjects (CURES-97) Diabetes Technology and Therapeutics. 2010;12(11):907–912.
30. Manrique, C., et al. , Hypertension and the cardiometabolic syndrome. J Clin Hypertens (Greenwich), 2005. 7(8): p. 471-6.
31.曾昭华等,西拉普利逆转SHR心血管重构作用及机制探讨.临床心血管病杂志.1999;15(6):270-272.
32.曾昭华,苏诚坚,抑平舒对高血压大鼠血管重构的干预.广东医学. 1998; 19(01): 8-9.
33. Whaley-Connell A, McCullough PA, Sowers JR.The role of oxidative stress in the metabolic syndrome. Rev Cardiovasc Med. 2011;12(1):21-9.
34. Wright JT, Bakris G, Greene T, et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. Journal of the American Medical Association. 2002;288(19):2421–2431.
35. Omae K, Ogawa T, Nitta K. Therapeutic advantage of angiotensin-converting enzyme inhibitors in patients with proteinuric chronic kidney disease. Heart and Vessels. 2010;25(3):203–208.
36. Matsui T, Yamagishi SI, Ueda S, Fukami K, Okuda S. Irbesartan inhibitsalbumin-elicited proximal tubular cell apoptosis and injury In vitro. Protein and Peptide Letters. 2010;17(1):74–77.
37. Kunz R, Friedrich C, Wolbers M, Mann JFE. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin-angiotensin system on proteinuria in renal disease. Annals of Internal Medicine. 2008;148(1):30–48.
38. Varagic, J., et al. , New angiotensins. J Mol Med, 2008. 86(6): p. 663-71.
39. Nakayama T, Kosugi T, Gersch M, Connor T, Sanchez-Lozada LG, Lanaspa MA, Roncal C, Perez-Pozo SE, Johnson RJ, Nakagawa T.Dietary fructose causes tubulointerstitial injury in the normal rat kidney. Am J Physiol Renal Physiol. 2010 Mar;298(3):F712-20.
40. Appel LJ, Wright Jr. JT, Greene T, et al. Intensive blood-pressure control in hypertensive chronic kidney disease. New England Journal of Medicine. 2010;363(10):918–929.
41. Petrovic, I., et al. , Ventricular and vascular remodelling effects of the angiotensin II receptor blocker telmisartan and/or the angiotensin-converting enzyme inhibitor ramipril in hypertensive patients. J Int Med Res. 2005;33:39A-49A.
42.汪新良等,替米沙坦对盐敏感性高血压大鼠血管重构的影响.中国心血管杂志.2005;06:405-409.
43. Kong X, Zhang DY, Wu HB, Li FXLosartan and pioglitazone ameliorate nephropathy in experimental metabolic syndrome rats. Biol Pharm Bull. 2011;34(5):693-9.
44. Chandrasekar, B., et al. , Interleukin-18-induced human coronary artery smooth muscle cell migration is dependent on NF-kappaB- and AP-1-mediated matrix metalloproteinase-9 expression and is inhibited by atorvastatin. J Biol Chem. 2006;281(22):15099-109.
45. Shimizu, K., et al. , Direct anti-inflammatory mechanisms contributeto attenuation of experimental allograft arteriosclerosis by statins. Circulation. 2003; 108(17): 2113-20.
46. .Reyes-Soffer G, Rondon-Clavo C, Ginsberg HN.Combination therapy with statin and fibrate in patients with dyslipidemia associated with insulin resistance, metabolic syndrome and type 2 diabetes mellitus. Expert Opin Pharmacother. 2011 Jun;12(9):1429-38.
47. picard, N., et al. , Origin of renal myofibroblasts in the model of unilateral ureter obstruction in the rat. 2008 ;130(1):141-55.
48. Efrati, S., et al., Rosiglitazone treatment attenuates renal tissue inflammation generated by urinary tract obstruction. 2009 ;14(2):189-97.
49. Eckel,RH,et al., The metabolic syndrome. Lancet. 2005,365:1415-1428.
50. Toblli,JE., et al., ACE inhiblitor and angiotensin typeⅠreceptor antagonist in combination reduce renal damage in obese Zucker rats.Kidney Int.2004;65:2343-2359.
51. Jakobisiak,M。,et al., Antitumor effects of the combination of cholesterol reducing drugs. Oncol Rep. 2011;26(1):169-76
1. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287(3):356-9.
2. Appel LJ, Wright Jr. JT, Greene T, et al. Intensive blood-pressure control in hypertensive chronic kidney disease. New England Journal of Medicine. 2010;363(10):918–929.
3. Tan CE, Ma S, Wai D, Chew SK, Tai ES.Can we apply the National Cholesterol Education Program Adult Treatment Panel definition of the metabolic syndrome to Asians? Diabetes Care. 2004;27(5):1182-6.
4. Palaniappan L, Carnethon M, Fortmann SP.Association between microalbuminuria and the metabolic syndrome: NHANES III.Am J Hypertens. 2003;16(11 Pt 1):952-8.
5.曹树臣,房铭.肥胖相关性肾病临床和病理特点分析.临床荟萃.2007;22(5):322-6.
6.董葆,陈文,程虹,等.肥胖相关性局灶节段性肾小球硬化症临床与病理表现.中华肾脏病杂志.2002;18:389-92.
7. Ballantyne GH,Gumbs A,Modlin IM.Changes in insul in resistance following bariatricsurgery and the adipoinsular axis:role oftheadipocytokines, lep tin, adiponectin and resistin.ObesSurg. 2005;15(5):692-9.
8. EL-Atat FA,Stas SN,McFarlane SI,et a1.The relationship betweenhyperinsulinemia.hypertension andprogressive renal disease.J Am SocNephrol. 2004;15:2816-27.
9. Efrati, S., et al., Rosiglitazone treatment attenuates renal tissue inflammation generated by urinary tract obstruction. 2009 ;14(2):189-97.
10.刘志红,黄燕飞.胰岛素抵抗与糖尿病肾病.肾脏病与透析肾移植杂志. 2002;11:164.
11. Ginsberg HN.Insulin resistance and cardiovasculardisease.J C1in Invest.2000;106:453-8.
12. Marcantoni C,Ma LJ,Fogo AB,et a1.Hypertensive nephrosclero-sis in AfricanAmericans versusCaucasians.KidneyInt.2002;62:172-80.
13. Kincaid—Smith P. Hypothesis: obesity and the insulin resistance syndrome playa major role in end-stage renal failure attributed to hypertension and labelled’hypertensive nephrosclerosis.J Hypertens. 2004;22:1051-5.
14. Whaley-Connell A, McCullough PA, Sowers JR.The role of oxidative stress in the metabolic syndrome. Rev Cardiovasc Med. 2011;12(1):21-9.
15. Bruce A. Strategies to prevent the metabolic syndrome at the population level: role of authorities and non-governmental bodies. Br J Nutr. 2000;83 Suppl 1:S181-6.
16. Appel LJ, Wright Jr. JT, Greene T, et al. Intensive blood-pressure control in hypertensive chronic kidney disease. New England Journal of Medicine. 2010;363(10):918–929.
2. Eckel,RH,et al., The metabolic syndrome. Lancet. 2005,365:1415-1428.
3. McNeill AM, Rosamond WD, Girman CJ, Golden SH, Schmidt MI, East HE, Ballantyne CM, Heiss G. The metabolic syndrome and 11-year risk of incident cardiovascular disease in the atherosclerosis risk in communities study. Diabetes Care. 2005;28:385-390.
4. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287(3):356-9.
5. Tan CE, Ma S, Wai D, Chew SK, Tai ES.Can we apply the National Cholesterol Education Program Adult Treatment Panel definition of the metabolic syndrome to Asians? Diabetes Care. 2004;27(5):1182-6.
6. Palaniappan L, Carnethon M, Fortmann SP.Association between microalbuminuria and the metabolic syndrome: NHANES III.Am J Hypertens. 2003;16(11 Pt 1):952-8.
7. Praga M, Hernández E, Morales E, Campos AP, Valero MA, Martínez MA, León M.Clinical features and long-term outcome of obesity-associated focal segmental glomerulosclerosis.Nephrol Dial Transplant. 2001;16(9):1790-8.
8. Scopinaro N, Adami GF, Papadia FS, Camerini G, Carlini F, Briatore L, D'Alessandro G, Parodi C, Weiss A, Andraghetti G, Catalano M, Cordera R.The Effects of Biliopancreatic Diversion on Type 2 Diabetes Mellitus in Patients with Mild Obesity (BMI 30-35 kg/m(2)) and Simple Overweight (BMI 25-30 kg/m (2)): A Prospective Controlled Study. Obes Surg. 2011 May 4. [Epub ahead of print]
9. Ballantyne GH,Gumbs A,Modlin IM.Changes in insul in resistance following bariatricsurgery and the adipoinsular axis:role oftheadipocytokines, lep tin, adiponectin and resistin.ObesSurg. 2005;15(5):692-9.
10. EL-Atat FA,Stas SN,McFarlane SI,et a1.The relationship between hyperinsulinemia.hypertension andprogressive renal disease.J Am SocNephrol. 2004;15:2816-27.
11. MuléG, Cottone S, Nardi E, Andronico G, Cerasola G. Metabolic syndrome in subjects with essential hypertension: relationships with subclinical cardiovascular and renal damage. Minerva Cardioangiol. 2006;54(2):173-94.
12. Ginsberg HN.Insulin resistance and cardiovasculardisease.J C1in Invest.2000;106:453-8.
13. Lastra-Lastra G, Sowers JR, Restrepo-Erazo K, Manrique-Acevedo C, Lastra-González G. Role of aldosterone and angiotensin II in insulin resistance: an update. Clin Endocrinol (Oxf). 2009;71:1-6.
14. Qi, W., et al.,Transforming growth factor-beta1 differentially mediates fibronectin and inflammatory cytokine expression in kidney tubular cells. Am J Physiol Renal Physiol.2006 ;291(5):F1070-7.
15. Marcantoni C,Ma LJ,Fogo AB,et a1.Hypertensive nephrosclero-sis in AfricanAmericans versusCaucasians.KidneyInt.2002;62:172-80.
16. Kincaid—Smith P. Hypothesis: obesity and the insulin resistance syndrome playa major role in end-stage renal failure attributed to hypertension and labelled’hypertensive nephrosclerosis.J Hypertens. 2004;22:1051-5.
17. Fujita T. Aldosterone and CKD in metabolic syndrome.Curr Hypertens Rep.2008,10 :421-3.
18. Nagase M, Yoshida S, Shibata S, Nagase T, Gotoda T, Ando K, Fujita T.Enhanced aldosterone signaling in the early nephropathy of rats withmetabolic syndrome: possible contribution of fat-derived factors. J Am Soc Nephrol. 2006 Dec;17(12):3438-46
19. Chen, Z., et al. , Simvastatin reduces neointimal thickening in low-density lipoprotein receptor-deficient mice after experimental angioplasty without changing plasma lipids. Circulation. 2002;106(1): 20-3.
20. Rule AD, Semret MH, Amer H, Cornell LD, Taler SJ, Lieske JC, Melton LJ 3rd, Stegall MD, Textor SC, Kremers WK, Lerman LO. Association of kidney function and metabolic risk factors with density of glomeruli on renal biopsy samples from living donors.Mayo Clin Proc. 2011 Apr;86(4):282-90.
21. Iglesias P, Díez JJ. Adipose tissue in renal disease: clinical significance and prognostic implications. Nephrology Dialysis Transplantation. 2010;25(7):2066–2077.
22. Gilbert EL, Ryan MJ.High dietary fat promotes visceral obesity and impaired endothelial function in female mice with systemic lupus erythematosus. Gend Med. 2011;8(2):150-5.
23. Ritz E. Metabolic syndrome and kidney disease. Blood Purification. 2008;26(1):59–62.
24. Lee SH, Park SA, Ko SH, et al. Insulin resistance and inflammation may have an additional role in the link between cystatin C and cardiovascular disease in type 2 diabetes mellitus patients. Metabolism. 2010;59(2):241–246.
25. Zapolski T, Waciński P, Kondracki B, Rychta E, Buraczyńska MJ, Wysokiński A. Uric acid as a link between renal dysfunction and both pro-inflammatory and prothrombotic state in patients with metabolic syndrome and coronary artery disease. Kardiol Pol. 2011;69(4):319-26.
26. Savino A, Pelliccia P, Chiarelli F, Mohn A. Obesity-related renal injury in childhood. Hormone Research in Paediatrics.2010;73(5):303–311.
27. Basi S, Lewis JB. Microalbuminuria as a target to improve cardiovascular and renal outcomes. American Journal of Kidney Diseases. 2006;47(6):927–946.
28. Shlipak MG, Katz R, Sarnak MJ, et al. Cystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease. Annals of Internal Medicine. 2006;145(4):237–246.
29. Surendar J, Indulekha K, Aravindhan V, Ganesan A, Mohan V. Association of cystatin-C with metabolic syndrome in normal glucose-tolerant subjects (CURES-97) Diabetes Technology and Therapeutics. 2010;12(11):907–912.
30. Manrique, C., et al. , Hypertension and the cardiometabolic syndrome. J Clin Hypertens (Greenwich), 2005. 7(8): p. 471-6.
31.曾昭华等,西拉普利逆转SHR心血管重构作用及机制探讨.临床心血管病杂志.1999;15(6):270-272.
32.曾昭华,苏诚坚,抑平舒对高血压大鼠血管重构的干预.广东医学. 1998; 19(01): 8-9.
33. Whaley-Connell A, McCullough PA, Sowers JR.The role of oxidative stress in the metabolic syndrome. Rev Cardiovasc Med. 2011;12(1):21-9.
34. Wright JT, Bakris G, Greene T, et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. Journal of the American Medical Association. 2002;288(19):2421–2431.
35. Omae K, Ogawa T, Nitta K. Therapeutic advantage of angiotensin-converting enzyme inhibitors in patients with proteinuric chronic kidney disease. Heart and Vessels. 2010;25(3):203–208.
36. Matsui T, Yamagishi SI, Ueda S, Fukami K, Okuda S. Irbesartan inhibitsalbumin-elicited proximal tubular cell apoptosis and injury In vitro. Protein and Peptide Letters. 2010;17(1):74–77.
37. Kunz R, Friedrich C, Wolbers M, Mann JFE. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin-angiotensin system on proteinuria in renal disease. Annals of Internal Medicine. 2008;148(1):30–48.
38. Varagic, J., et al. , New angiotensins. J Mol Med, 2008. 86(6): p. 663-71.
39. Nakayama T, Kosugi T, Gersch M, Connor T, Sanchez-Lozada LG, Lanaspa MA, Roncal C, Perez-Pozo SE, Johnson RJ, Nakagawa T.Dietary fructose causes tubulointerstitial injury in the normal rat kidney. Am J Physiol Renal Physiol. 2010 Mar;298(3):F712-20.
40. Appel LJ, Wright Jr. JT, Greene T, et al. Intensive blood-pressure control in hypertensive chronic kidney disease. New England Journal of Medicine. 2010;363(10):918–929.
41. Petrovic, I., et al. , Ventricular and vascular remodelling effects of the angiotensin II receptor blocker telmisartan and/or the angiotensin-converting enzyme inhibitor ramipril in hypertensive patients. J Int Med Res. 2005;33:39A-49A.
42.汪新良等,替米沙坦对盐敏感性高血压大鼠血管重构的影响.中国心血管杂志.2005;06:405-409.
43. Kong X, Zhang DY, Wu HB, Li FXLosartan and pioglitazone ameliorate nephropathy in experimental metabolic syndrome rats. Biol Pharm Bull. 2011;34(5):693-9.
44. Chandrasekar, B., et al. , Interleukin-18-induced human coronary artery smooth muscle cell migration is dependent on NF-kappaB- and AP-1-mediated matrix metalloproteinase-9 expression and is inhibited by atorvastatin. J Biol Chem. 2006;281(22):15099-109.
45. Shimizu, K., et al. , Direct anti-inflammatory mechanisms contributeto attenuation of experimental allograft arteriosclerosis by statins. Circulation. 2003; 108(17): 2113-20.
46. .Reyes-Soffer G, Rondon-Clavo C, Ginsberg HN.Combination therapy with statin and fibrate in patients with dyslipidemia associated with insulin resistance, metabolic syndrome and type 2 diabetes mellitus. Expert Opin Pharmacother. 2011 Jun;12(9):1429-38.
47. picard, N., et al. , Origin of renal myofibroblasts in the model of unilateral ureter obstruction in the rat. 2008 ;130(1):141-55.
48. Efrati, S., et al., Rosiglitazone treatment attenuates renal tissue inflammation generated by urinary tract obstruction. 2009 ;14(2):189-97.
49. Eckel,RH,et al., The metabolic syndrome. Lancet. 2005,365:1415-1428.
50. Toblli,JE., et al., ACE inhiblitor and angiotensin typeⅠreceptor antagonist in combination reduce renal damage in obese Zucker rats.Kidney Int.2004;65:2343-2359.
51. Jakobisiak,M。,et al., Antitumor effects of the combination of cholesterol reducing drugs. Oncol Rep. 2011;26(1):169-76
1. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287(3):356-9.
2. Appel LJ, Wright Jr. JT, Greene T, et al. Intensive blood-pressure control in hypertensive chronic kidney disease. New England Journal of Medicine. 2010;363(10):918–929.
3. Tan CE, Ma S, Wai D, Chew SK, Tai ES.Can we apply the National Cholesterol Education Program Adult Treatment Panel definition of the metabolic syndrome to Asians? Diabetes Care. 2004;27(5):1182-6.
4. Palaniappan L, Carnethon M, Fortmann SP.Association between microalbuminuria and the metabolic syndrome: NHANES III.Am J Hypertens. 2003;16(11 Pt 1):952-8.
5.曹树臣,房铭.肥胖相关性肾病临床和病理特点分析.临床荟萃.2007;22(5):322-6.
6.董葆,陈文,程虹,等.肥胖相关性局灶节段性肾小球硬化症临床与病理表现.中华肾脏病杂志.2002;18:389-92.
7. Ballantyne GH,Gumbs A,Modlin IM.Changes in insul in resistance following bariatricsurgery and the adipoinsular axis:role oftheadipocytokines, lep tin, adiponectin and resistin.ObesSurg. 2005;15(5):692-9.
8. EL-Atat FA,Stas SN,McFarlane SI,et a1.The relationship betweenhyperinsulinemia.hypertension andprogressive renal disease.J Am SocNephrol. 2004;15:2816-27.
9. Efrati, S., et al., Rosiglitazone treatment attenuates renal tissue inflammation generated by urinary tract obstruction. 2009 ;14(2):189-97.
10.刘志红,黄燕飞.胰岛素抵抗与糖尿病肾病.肾脏病与透析肾移植杂志. 2002;11:164.
11. Ginsberg HN.Insulin resistance and cardiovasculardisease.J C1in Invest.2000;106:453-8.
12. Marcantoni C,Ma LJ,Fogo AB,et a1.Hypertensive nephrosclero-sis in AfricanAmericans versusCaucasians.KidneyInt.2002;62:172-80.
13. Kincaid—Smith P. Hypothesis: obesity and the insulin resistance syndrome playa major role in end-stage renal failure attributed to hypertension and labelled’hypertensive nephrosclerosis.J Hypertens. 2004;22:1051-5.
14. Whaley-Connell A, McCullough PA, Sowers JR.The role of oxidative stress in the metabolic syndrome. Rev Cardiovasc Med. 2011;12(1):21-9.
15. Bruce A. Strategies to prevent the metabolic syndrome at the population level: role of authorities and non-governmental bodies. Br J Nutr. 2000;83 Suppl 1:S181-6.
16. Appel LJ, Wright Jr. JT, Greene T, et al. Intensive blood-pressure control in hypertensive chronic kidney disease. New England Journal of Medicine. 2010;363(10):918–929.