NGAL、Klotho基因与妊娠期高血压疾病及AKI关系的研究

发布时间：2018-12-13 16:37

【摘要】：[目的]研究妊娠期高血压疾病合并急性肾损伤(Acute Kidney Injury, AKI)孕妇血液中NGAL、Klotho与妊娠期高血压疾病合并AKI的关系及Klotho在AKI发病中的作用。[方法]将2016年4月至7月在昆明医科大学第一附属医院产科住院的孕妇79例根据孕妇是否合并妊娠期高血压疾病及AKI分为3组:正常妊娠组(30例)、妊娠期高血压疾病组(40例)、妊娠期高血压疾病合并AKI组(9例)。采用PCR方法检测以上三组人群血液中klotho基因的表达,Elisa方法检测以上三组人群血清中Klotho蛋白、NGAL,酶法测以上三组人群血清中MDA、SOD,分别比较各组间的差异。[结果]1. Elisa方法显示,妊娠期高血压疾病合并AKI组、妊娠期高血压疾病组、正常妊娠组血清NGAL浓度分别为(234. 50土90. 85)ng/ml、(181. 25±65. 86)ng/ml、(113.23±40.87) ng/ml,差异有统计学意义(P0.001),进一步行两两比较三组间差异均有统计学意义。且血清NGAL与血肌酐(r=0.526, P0.001)、尿素氮(r=0. 324,P=0. 004)、尿酸(r=0. 429, P0. 001)、收缩压(r=0. 465, P0. 001)、舒张压(r=0.47,P0.001)、24h尿蛋白(r=0.253,P=0.024)成正相关。2. PCR及Elisa方法显示,妊娠期高血压疾病合并AKI组、妊娠期高血压疾病组、正常妊娠组血液中Klotho/ β -actin值分别为(0. 34±0. 02)、(0. 46土0. 02)、(0.64±0.04),Klotho蛋白浓度分别为(5.73±0.90) pg/ml、(8.44±1.05)pg/ml、(12.14土 1.47) pg/ml,差异有统计学意义(P0. 001),进一步行两两比较三组间差异均有统计学意义。且总体血清中Klotho蛋白浓度与血肌酐呈负相关(r=-0.7, P0.001)。3.酶法显示,妊娠期高血压疾病合并AKI组、妊娠期高血压疾病组、正常妊娠组血清SOD浓度分别为(74.80±3.28) U/ml、(80.32±9.88) U/ml、(85.83±5.89)U/ml,差异有统计学意义(P=0.001 ) , MDA浓度分别为(6.80±0.59)nmol/ml、(5.42±1.14) nmol/ml、(4.62±0. 67) nmol/ml,差异有统计学意义(P0. 001 ),进一步行两两比较三组间差异均有统计学意义。且总体MDA浓度与Klotho蛋白浓度呈负相关(r=-0. 455,P0.001)。4.中介效应分析发现:Klotho蛋白对肌酐的影响有部分直接效应,Klotho蛋白对肌酐的影响效应部分是通过中间变量MDA产生的,MDA部分中介效应对总效应的贡献率为17. 54%。[结论]1.妊娠期高血压疾病合并AKI组及妊娠期高血压疾病组血清中NGAL较正常妊娠组升高,两两比较三组间差异均有统计学意义,总体血清NGAL与血肌酐、尿素氮、尿酸、收缩压、舒张压、24h尿蛋白呈正相关,提示NGAL可能参与了妊娠期高血压疾病的发病,且NGAL可用于妊娠期高血压疾病合并AKI的早期诊断。2. Klotho蛋白与血肌酐呈负相关,妊娠期高血压疾病合并AKI孕妇血液中Klotho基因及蛋白表达降低,说明Klotho在妊娠期高血压疾病合并AKI的发病机制中具有重要作用。3. Klotho表达减少及其减少所致的氧化应激增强可能是妊娠期高血压疾病合并AKI发生的原因。
[Abstract]:[objective] to study the relationship between NGAL,Klotho in blood of pregnant women with hypertensive disorder complicating pregnancy with acute renal injury (Acute Kidney Injury, AKI) and hypertensive disorder complicating pregnancy with AKI and the role of Klotho in the pathogenesis of AKI. [methods] Seventy-nine pregnant women hospitalized in obstetrics department of the first affiliated Hospital of Kunming Medical University from April to July 2016 were divided into 3 groups: normal pregnancy group (n = 30) according to whether the pregnant women were complicated with hypertensive disorder complicating pregnancy and AKI. Hypertensive disorder complicating pregnancy group (40 cases), hypertensive disorder complicating pregnancy with AKI group (9 cases). PCR method was used to detect the expression of klotho gene in the blood of the above three groups, Elisa method was used to detect the Klotho protein in the serum of the above three groups, and NGAL, enzyme method was used to detect the MDA,SOD, in the serum of the three groups. [result] 1. Elisa method showed that the serum NGAL levels of hypertensive complicating disease complicating AKI group, gestational hypertension disorder group and normal pregnancy group were respectively (234. 4%). 50 卤90. 85) ng/ml, (181. 25 卤65. 86) ng/ml, (113.23 卤40.87) ng/ml, was significantly different (P0. 001). Serum NGAL and serum creatinine (rt0. 526, P0. 001), urea nitrogen (r0. 01). 324g. Uric acid. 429, P0. 001), systolic pressure (rc0. 465, P0. There was a positive correlation between diastolic blood pressure (r = 0.47) and 24 h urinary protein (r = 0.253). PCR and Elisa showed that the serum Klotho/ 尾-actin values of hypertensive disorder complicating pregnancy combined with AKI group, gestational hypertension disorder group and normal pregnancy group were (0. 5%). 34 卤0. 02), (0. 46 to 0. The protein concentration of 02), (0.64 卤0.04), Klotho was (5.73 卤0.90) pg/ml, (8.44 卤1.05) pg/ml, (12.14 卤1.47) pg/ml, respectively. The differences between the three groups were statistically significant. There was a negative correlation between serum Klotho protein and serum creatinine (r-0.7, P 0. 001). The levels of serum SOD were (74.80 卤3.28) U / ml, (80.32 卤9.88) U / ml, (85.83 卤5.89) U / ml, respectively. The difference was statistically significant (P0. 001), MDA concentration was (6. 80 卤0. 59) nmol/ml, (5. 42 卤1. 14) nmol/ml,) (4. 62 卤0. 2). 67) the difference of nmol/ml, was statistically significant (P0. The differences between the three groups were statistically significant. There was a negative correlation between total MDA concentration and Klotho protein concentration (r = -0). 455nb. P0.001) 4. The results showed that the effect of Klotho protein on creatinine was partly direct, the effect of Klotho protein on creatinine was partly produced by the intermediate variable MDA, and the contribution rate of MDA partial mediation effect to the total effect was 17.7%. 54. [conclusion] 1. Compared with normal pregnancy group, the levels of serum NGAL in pregnancy with hypertension complicating AKI group and gestational hypertension disorder group were significantly higher than those in normal pregnancy group. The total serum NGAL was significantly different from serum creatinine, urea nitrogen, uric acid, systolic blood pressure, diastolic blood pressure (DBP), serum creatinine, urea nitrogen, uric acid, systolic blood pressure and diastolic blood pressure. The positive correlation of 24 hours urine protein suggests that NGAL may be involved in the pathogenesis of hypertensive disorder complicating pregnancy, and NGAL can be used in the early diagnosis of hypertensive disorder complicating pregnancy with AKI. 2. Klotho protein was negatively correlated with serum creatinine, and the expression of Klotho gene and protein in the blood of hypertensive disorder complicating pregnancy with AKI decreased, indicating that Klotho plays an important role in the pathogenesis of hypertensive disorder complicating pregnancy with AKI. 3. The decrease of Klotho expression and the increase of oxidative stress may be the cause of hypertensive disorder complicating pregnancy with AKI.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R714.246

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