摘要目的 通过测定正常妊娠孕妇、子痫前期糖代谢正常患者、妊娠期糖尿病( gestational diabetes mellitus,GDM)患者及子痫前期合并GDM患者血清中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)水平,探讨NGAL与子痫前期、GDM孕妇糖代谢和脂代谢的相关性. 方法 选取2009年12月至2010年11月在广州医学院附属广东省妇女儿童医院定期产前检查并分娩的单胎正常妊娠孕妇、子痫前期糖代谢正常患者及GDM患者各77例,子痫前期合并GDM患者32例.测定所有研究对象血清NGAL、空腹血精、空腹胰岛素、脂代谢参数、尿酸、肌酐、乳酸脱氢酶及24 h尿蛋白等指标,测量血压,计算体重指数(body mass index,BMI),用稳态模型评估法计算胰岛素抵抗指数(homeostasis model assessment for insulin resistance,HOMA-IR)评价胰岛索敏感性.正态分布资料用单因素方差分析及Student's t检验进行比较,非正态分布资料用Kruskal-Wallis H检验和Mann-Whitney U检验进行比较.采用Spearman相关分析和多元逐步回归法进一步分析. 结果 子痫前期合并GDM组孕妇血清NGAL水平高于子痫前期糖代谢正常组[(70.82±20.02) ng/ml与(56.17±18.22)ng/ml,t=3.65,P＜0.01]、GDM组[(43.99±14.82) ng/ml,t=5.97,P＜0.01]及正常妊娠组[(17.80±5.78) ng/ml,t=14.76,P＜0.01)；子痫前期糖代谢正常组血清NGAL水平高于GDM组(t=5.90,P＜0.01)；子痫前期合并GDM组和子痫前期糖代谢正常组中,子痫前期重度组血清NGAL水平均高于子痫前期轻度组[(76.44±28.06)ng/ml与(60.15±25.86) ng/ml,t=2.82,P＜0.05; (61.61±37.14) ng/ml与(46.30±13.97) ng/ml,t=4.74,P＜0.01].校正孕周、孕妇年龄后血清NGAL水平与孕前BMI(r=0.335,P＜0.01)、入组BMI(r=0.427,P＜0.01)、入组收缩压(r=0.648,P＜0.01),入组舒张压(r=0.664,P＜0.01)、空腹血糖(r=0.320,P＜0.01)、空腹胰岛素(r=0.381,P＜0.01)、HOMA-IR(r=0.399,P＜0.01)、甘油三酯(r=0.405,P＜0.01)、总胆固醇(r=0.145,P＜0.05)、游离脂肪酸(r=0.335,P＜0.01)、尿酸(r=0.292,P＜0.01)、肌酐(r=0.226,P＜0.01)及24 h尿蛋白(r=0.436,P＜0.001)呈正相关,与高密度脂蛋白胆固醇(r=-0.189,P=0.008)呈负相关.多元逐步回归分析显示,入组收缩压(β=0.251,P＜0.01),入组舒张压(β=0.351,P＜0.01)、HOMA-IR(β=0.265,P＜0.01)、24 h尿蛋白(β=0.140,P＜0.05)是血清NGAL的独立相关因素. 结论 子痫前期及GDM患者血清NGAL水平显著升高,与糖脂代谢及血管内皮功能失调相关,提示NGAL可能在子痫前期及GDM的病理生理过程中发挥作用.

abstractsObjective To investigate the relationship of serum neutrophil gelatinase associatedlipocalin (NGAL) levels among preeclamptic women with or without gestational diabetes mellitus (GDM),GDM and healthy pregnant controls. Methods This study included 263 singleton pregnant women who visited the antenatal chinics in Guangdong Women and Children's Hospital and Health Instutite Affiliated to Guangzhou Medical College from December 2009 to November 2010,77 healthy pregnant women,77 women with preeclampsia,77 women with GDM and 32 women complicated with both preeclampsia and GDM.Blood pressure,height and body weight of all subjects were measured.Peripheral blood samples were collected to detect serum NGAL,parameters of glycolipid metabolism,24-hour urine protein content,uric acid,creatinine and lactate dehydrogenase.Maternal levels of serum NGAL were quantified by enzyme-linked immunosorbent assay.Meanwhile,body mass index (BMI) and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. Data under normal distribution were analyzed with one-way ANOVA and Student's t test,and those under abnormal distribution were compared with Kruskal-Wallis H or Mann-Whitney U test. Results The preeclampsia with GDM group had higher serum NGAL level [(70.82±20.02) ng/ml] as compared with preeclampsia group [(56.17 ±18.22) ng/ml],GDM group [(43.99 ± 14.82) ng/ml] and healthy pregnant control group [(17.80±5.78) ng/ml],t=3.65,5.97,14.76,P＜0.01,respectively.The NGAL levels in preeclampsia group without GDM were higher than in GDM group (t=5.90,P＜0.01).In both the preeclampsia with and without GDM groups,NGAL levels in patients with severe preeclampsia were higher than in the mild ones [(76.44±28.06) ng/ml or(60.15±25.86) ng/ml,t=2.82,P＜0.05; (61.61±37.14) ng/ml or (46.30±13.97) ng/ml,t=4.74,P＜0.01].After adjusted by gesrational weeks and maternal age,NGAL level was positively correlated with BMI before pregnancy (r=0.335,P＜0.01),BMI after pregnancy (r=0.427,P＜0.01),systolic blood pressure (r=0.648,P＜0.01),diastolic blood pressure (r=0.664,P＜0.01),fasting blood glucose (r=0.320,P＜0.01),fasting insulin level (r=0.381,P＜0.01),HOMA-IR (r=0.399,P＜0.01),triglyceride level (r=0.405,P＜0.01),total cholesterol (r=0.145,P＜0.05),free fatty acids (r=0.335,P＜0.01),uric acid (r =0.292,P＜0.01),creatinine (r =0.226,P ＜ 0.01),and 24-hour urine protein content (r =0.436,P＜0.01),and negatively correlated with high density lipoprotein-cholesterol (r=-0.189,P =0.008).Stepwise regression analysis showed that systolic blood pressure (β =0.251,P ＜ 0.01),diastolic blood pressure (β=0.351,P＜0.01),HOMA-IR (β=0.265,P＜0.01) and 24-hour urine protein content (β=0.140,P=0.011) were independent factors of NGAL. Conclusions Serum NGAL levels increase significantly in patients with preeclampsia or GDM,and are correlated with parameters of glycolipid metabolism end endothelial dysfunction,which might play a role in the pathogenesis of preeclampsia and GDM.