NGAL、Klotho基因與妊娠期高血壓疾病及AKI關(guān)系的研究
發(fā)布時(shí)間：2018-12-13 16:37
【摘要】：[目的]研究妊娠期高血壓疾病合并急性腎損傷(Acute Kidney Injury, AKI)孕婦血液中NGAL、Klotho與妊娠期高血壓疾病合并AKI的關(guān)系及Klotho在AKI發(fā)病中的作用。[方法]將2016年4月至7月在昆明醫(yī)科大學(xué)第一附屬醫(yī)院產(chǎn)科住院的孕婦79例根據(jù)孕婦是否合并妊娠期高血壓疾病及AKI分為3組:正常妊娠組(30例)、妊娠期高血壓疾病組(40例)、妊娠期高血壓疾病合并AKI組(9例)。采用PCR方法檢測以上三組人群血液中klotho基因的表達(dá),Elisa方法檢測以上三組人群血清中Klotho蛋白、NGAL,酶法測以上三組人群血清中MDA、SOD,分別比較各組間的差異。[結(jié)果]1. Elisa方法顯示,妊娠期高血壓疾病合并AKI組、妊娠期高血壓疾病組、正常妊娠組血清NGAL濃度分別為(234. 50土90. 85)ng/ml、(181. 25±65. 86)ng/ml、(113.23±40.87) ng/ml,差異有統(tǒng)計(jì)學(xué)意義(P0.001),進(jìn)一步行兩兩比較三組間差異均有統(tǒng)計(jì)學(xué)意義。且血清NGAL與血肌酐(r=0.526, P0.001)、尿素氮(r=0. 324,P=0. 004)、尿酸(r=0. 429, P0. 001)、收縮壓(r=0. 465, P0. 001)、舒張壓(r=0.47,P0.001)、24h尿蛋白(r=0.253,P=0.024)成正相關(guān)。2. PCR及Elisa方法顯示,妊娠期高血壓疾病合并AKI組、妊娠期高血壓疾病組、正常妊娠組血液中Klotho/ β -actin值分別為(0. 34±0. 02)、(0. 46土0. 02)、(0.64±0.04),Klotho蛋白濃度分別為(5.73±0.90) pg/ml、(8.44±1.05)pg/ml、(12.14土 1.47) pg/ml,差異有統(tǒng)計(jì)學(xué)意義(P0. 001),進(jìn)一步行兩兩比較三組間差異均有統(tǒng)計(jì)學(xué)意義。且總體血清中Klotho蛋白濃度與血肌酐呈負(fù)相關(guān)(r=-0.7, P0.001)。3.酶法顯示,妊娠期高血壓疾病合并AKI組、妊娠期高血壓疾病組、正常妊娠組血清SOD濃度分別為(74.80±3.28) U/ml、(80.32±9.88) U/ml、(85.83±5.89)U/ml,差異有統(tǒng)計(jì)學(xué)意義(P=0.001 ) , MDA濃度分別為(6.80±0.59)nmol/ml、(5.42±1.14) nmol/ml、(4.62±0. 67) nmol/ml,差異有統(tǒng)計(jì)學(xué)意義(P0. 001 ),進(jìn)一步行兩兩比較三組間差異均有統(tǒng)計(jì)學(xué)意義。且總體MDA濃度與Klotho蛋白濃度呈負(fù)相關(guān)(r=-0. 455,P0.001)。4.中介效應(yīng)分析發(fā)現(xiàn):Klotho蛋白對肌酐的影響有部分直接效應(yīng),Klotho蛋白對肌酐的影響效應(yīng)部分是通過中間變量MDA產(chǎn)生的,MDA部分中介效應(yīng)對總效應(yīng)的貢獻(xiàn)率為17. 54%。[結(jié)論]1.妊娠期高血壓疾病合并AKI組及妊娠期高血壓疾病組血清中NGAL較正常妊娠組升高,兩兩比較三組間差異均有統(tǒng)計(jì)學(xué)意義,總體血清NGAL與血肌酐、尿素氮、尿酸、收縮壓、舒張壓、24h尿蛋白呈正相關(guān),提示NGAL可能參與了妊娠期高血壓疾病的發(fā)病,且NGAL可用于妊娠期高血壓疾病合并AKI的早期診斷。2. Klotho蛋白與血肌酐呈負(fù)相關(guān),妊娠期高血壓疾病合并AKI孕婦血液中Klotho基因及蛋白表達(dá)降低,說明Klotho在妊娠期高血壓疾病合并AKI的發(fā)病機(jī)制中具有重要作用。3. Klotho表達(dá)減少及其減少所致的氧化應(yīng)激增強(qiáng)可能是妊娠期高血壓疾病合并AKI發(fā)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 鹵90. 85) ng/ml, (181. 25 鹵65. 86) ng/ml, (113.23 鹵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 鹵0. 02), (0. 46 to 0. The protein concentration of 02), (0.64 鹵0.04), Klotho was (5.73 鹵0.90) pg/ml, (8.44 鹵1.05) pg/ml, (12.14 鹵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 鹵3.28) U / ml, (80.32 鹵9.88) U / ml, (85.83 鹵5.89) U / ml, respectively. The difference was statistically significant (P0. 001), MDA concentration was (6. 80 鹵0. 59) nmol/ml, (5. 42 鹵1. 14) nmol/ml,) (4. 62 鹵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.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R714.246
[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 鹵90. 85) ng/ml, (181. 25 鹵65. 86) ng/ml, (113.23 鹵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 鹵0. 02), (0. 46 to 0. The protein concentration of 02), (0.64 鹵0.04), Klotho was (5.73 鹵0.90) pg/ml, (8.44 鹵1.05) pg/ml, (12.14 鹵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 鹵3.28) U / ml, (80.32 鹵9.88) U / ml, (85.83 鹵5.89) U / ml, respectively. The difference was statistically significant (P0. 001), MDA concentration was (6. 80 鹵0. 59) nmol/ml, (5. 42 鹵1. 14) nmol/ml,) (4. 62 鹵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.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R714.246
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