本文選題：IgA腎病 + 足細(xì)胞　； 參考：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:近年來,足細(xì)胞損傷在Ig A腎病(Ig A nephropathy,Ig AN)中的致病作用受到廣泛關(guān)注。本研究通過檢測Ig AN腎組織腫瘤壞死因子α(tumor necrosis factor-α,TNF-α)、白細(xì)胞介素6(interleukin-6,IL-6)、Wilms腫瘤蛋白(Wilm’s tumor 1,WT1)的表達(dá)變化及尿液中TNF-α、IL-6的水平,并通過收集臨床和病理資料,擬探討TNF-α、IL-6在Ig AN足細(xì)胞損傷及疾病發(fā)生發(fā)展中的作用。方法:選取2015年12月至2016年12月在河北醫(yī)科大學(xué)第二醫(yī)院住院,行腎穿刺活檢術(shù),根據(jù)臨床和病理資料確診為Ig AN患者40例。均除外過敏性紫癜、自身免疫性疾病、肝硬化、銀屑病、強直性脊柱炎等繼發(fā)性Ig AN,并除外合并其他腎病,如糖尿病腎病等。患者的病理指標(biāo)按Ig A腎病的Lee氏分級,并參照Katafuchi等的方法對腎小球、小管間質(zhì)等進(jìn)行半定量積分。分別分析各臨床指標(biāo)與不同病理類型及病理改變積分之間的關(guān)系。按Lee氏腎組織改變分為I~V級,其中I~III級為一組,IV、V級為另外一組。收集患者一般資料:性別、年齡、血壓;臨床指標(biāo):尿蛋白、血白蛋白、血肌酐、尿酸、β2-微球蛋白、總膽固醇、甘油三酯、空腹血糖、尿滲透壓,應(yīng)用簡化的MDRD公式評估腎小球濾過率。河北醫(yī)科大學(xué)第二醫(yī)院體檢中心健康體檢者40例作為對照組。河北醫(yī)科大學(xué)第二醫(yī)院泌尿外科腎臟腫瘤切除術(shù)后,遠(yuǎn)離病灶部位的腎臟組織10例作為正常組織對照。采用酶聯(lián)免疫吸附法測定尿TNF-α、尿IL-6水平。尿TNF-α、尿IL-6濃度均除以尿肌酐值進(jìn)行校正。應(yīng)用免疫組織化學(xué)法做TNF-α、IL-6、WT1的腎組織染色,并用圖像分析軟件進(jìn)行分析。應(yīng)用IBM spss21.0統(tǒng)計學(xué)軟進(jìn)行統(tǒng)計學(xué)分析。結(jié)果:1研究對象的一般資料:(1)與對照組相比,Ig AN患者收縮壓、舒張壓、血肌酐、尿酸、β2-微球蛋白、總膽固醇、甘油三酯明顯升高,血白蛋白、e GFR明顯降低,差異有統(tǒng)計學(xué)意義(P0.05),兩組患者性別、年齡、空腹血糖的差異無統(tǒng)計學(xué)意義(P0.05)。(2)實驗組兩組間比較:與I~III級患者相比,Ig AN IV、V級患者收縮壓、舒張壓、尿蛋白、血肌酐、尿酸、β2-微球蛋白、總膽固醇、甘油三酯明顯升高,血白蛋白、e GFR、尿滲透壓明顯降低,差異有統(tǒng)計學(xué)意義(P0.05),兩組間性別、年齡、空腹血糖的差異均無統(tǒng)計學(xué)意義(P0.05)。2 TNF-α的變化:(1)腎組織中TNF-α的表達(dá):TNF-α主要表達(dá)于近端小管上皮細(xì)胞胞漿內(nèi),其中以萎縮的近端小管最明顯,成黃色或棕黃色顆粒。實驗組兩組比較,I~III級Ig AN患者腎組織中TNF-α的平均光密度為(17.12±5.22),IV、V級Ig AN患者腎組織中TNF-α的平均光密度為(35.15±9.42),差異有統(tǒng)計學(xué)意義(P0.05)。(2)Ig AN患者尿TNF-α的水平為(23.18±10.09)ng/mg·Cr,正常對照組尿TNF-α的水平為(11.92±2.53)ng/mg·Cr,二者相比,實驗組明顯升高,差異有統(tǒng)計學(xué)意義(P0.05);實驗組兩組比較,I~III級Ig AN患者尿TNF-α的水平為(15.70±4.98)ng/mg·Cr,IV、V級Ig AN患者尿TNF-α的水平為(29.95±8.49)ng/mg·Cr,病理類型越重,尿TNF-α的水平越高,差異有統(tǒng)計學(xué)意義(P0.05)。3 IL-6的變化:(1)腎組織中IL-6的表達(dá):IL-6主要表達(dá)于近端小管上皮細(xì)胞胞漿內(nèi),其中以萎縮的近端小管最明顯,成黃色或棕黃色顆粒。實驗組兩組比較,I~III級Ig AN患者腎組織中IL-6的平均光密度為(24.25±11.98),IV、V級Ig AN患者腎組織中IL-6的平均光密度為(52.57±20.15),差異有統(tǒng)計學(xué)意義(P0.05)。(2)Ig AN患者尿IL-6的水平為(20.45±10.34)pg/mg·Cr,正常對照組尿IL-6的水平為(5.90±2.31)pg/mg·Cr,二者相比,實驗組明顯升高,差異有統(tǒng)計學(xué)意義(P0.05);實驗組兩組比較,I~III級Ig AN患者尿IL-6的水平為(13.18±5.30)ng/mg·Cr,IV、V級Ig AN患者尿IL-6的水平為(27.01±9.36)ng/mg·Cr,病理類型越重,尿IL-6的水平越高,差異有統(tǒng)計學(xué)意義(P0.05)。4腎組織中WT1的表達(dá):WT1主要表達(dá)于正常足細(xì)胞的細(xì)胞核,成黃色或棕黃色顆粒。實驗組兩組比較,I~III級Ig AN患者腎組織中WT1的平均光密度為(14.15±5.30),IV、V級Ig AN患者腎組織中WT1的平均光密度為(9.44±3.51),差異有統(tǒng)計學(xué)意義(P0.05)。5相關(guān)性分析結(jié)果:(1)腎組織中TNF-α與各指標(biāo)相關(guān)分析:Ig AN患者腎組織中TNF-α的表達(dá)與收縮壓、舒張壓、尿蛋白、血肌酐、尿酸、β2-微球蛋白、總膽固醇、甘油三酯、系膜增生、腎小球硬化度、間質(zhì)纖維化、腎小管萎縮、IL-6陽性表達(dá)率、尿TNF-α、尿IL-6呈正相關(guān),與血白蛋白、e GFR、尿滲透壓、WT1陽性表達(dá)率呈負(fù)相關(guān),與年齡、空腹血糖無明顯相關(guān)性。(2)尿TNF-α與各指標(biāo)相關(guān)分析:Ig AN患者尿TNF-α水平與收縮壓、舒張壓、尿蛋白、血肌酐、尿酸、β2-微球蛋白、總膽固醇、系膜增生、腎小球硬化度、間質(zhì)纖維化、腎小管萎縮、TNF-α陽性表達(dá)率、IL-6陽性表達(dá)率、尿IL-6呈正相關(guān),與血白蛋白、e GFR、尿滲透壓、w T1陽性表達(dá)率呈負(fù)相關(guān),與年齡、空腹血糖、甘油三酯無明顯相關(guān)性。(3)腎組織中IL-6與各指標(biāo)相關(guān)分析:Ig AN患者腎組織中IL-6的表達(dá)與收縮壓、舒張壓、尿蛋白、血肌酐、尿酸、β2-微球蛋白、總膽固醇、系膜增生、腎小球硬化度、間質(zhì)纖維化、腎小管萎縮、TNF-α陽性表達(dá)率、尿TNF-α、尿IL-6呈正相關(guān),與血白蛋白、e GFR、尿滲透壓、w T1陽性表達(dá)率呈負(fù)相關(guān),與年齡、空腹血糖、甘油三酯無明顯相關(guān)性。(4)尿IL-6與各指標(biāo)相關(guān)分析:Ig AN患者尿IL-6水平與收縮壓、舒張壓、尿蛋白、血肌酐、尿酸、β2-微球蛋白、總膽固醇、系膜增生、腎小球硬化度、間質(zhì)纖維化、腎小管萎縮、TNF-α陽性表達(dá)率、IL-6陽性表達(dá)率、尿TNF-α呈正相關(guān),與血白蛋白、e GFR、尿滲透壓、w T1陽性表達(dá)率呈負(fù)相關(guān),與年齡、空腹血糖、甘油三酯無明顯相關(guān)性。結(jié)論:1 TNF-α、IL-6加重Ig AN足細(xì)胞損傷,促進(jìn)疾病進(jìn)展。2尿液TNF-α、IL-6的水平有望成為評價腎組織局部TNF-α、IL-6代謝的可靠指標(biāo),為臨床監(jiān)測Ig AN進(jìn)展提供一項無創(chuàng)傷的檢查方法。
[Abstract]:Objective: in recent years, the pathogenicity of podocyte injury in Ig A nephropathy (Ig A nephropathy, Ig AN) has been widely concerned. This study was conducted by detecting the expression of Ig AN renal tissue tumor necrosis factor alpha (tumor necrosis factor- alpha), interleukin 6, and the changes in the expression of tumor protein 1. NF- alpha, IL-6 level, and by collecting clinical and pathological data, we should explore the role of TNF- alpha and IL-6 in Ig AN foot cell injury and the development of disease. Methods: from December 2015 to December 2016, the second hospital of Hebei Medical University was hospitalized, and the renal biopsy was performed. According to the clinical and pathological data, 40 cases of Ig AN patients were confirmed. All of them were excluded. Anaphylactoid purpura, autoimmune disease, cirrhosis, psoriasis, ankylosing spondylitis, and other secondary Ig AN, except for other nephropathy, such as diabetic nephropathy. The pathological indexes of the patients are classified according to Lee's grade of Ig A nephropathy, and the glomeruli, tubulointerstitium, etc. are integrated with the methods of Katafuchi and so on. The relationship between the standard and the score of pathological changes and pathological changes was divided into I~V grade according to Lee's renal tissue changes, of which I~III was a group, IV, and V was another group. The general data of the patients were collected: sex, age, blood pressure, and clinical indicators: urinary protein, serum albumin, serum creatinine, uric acid, beta 2- microglobulin, total cholesterol, triglyceride, fasting blood glucose The urine osmotic pressure was used to evaluate the glomerular filtration rate by the simplified MDRD formula. 40 cases of healthy physical examination at the physical examination center of the second hospital of Hebei Medical University were used as the control group. After the kidney tumor resection in the Department of Urology of the second hospital of Hebei Medical University, 10 cases of renal tissue far away from the lesion were used as normal tissue control. The enzyme linked immunosorbent assay was used. Urine TNF- alpha, urine IL-6 level, urine TNF- alpha, urine IL-6 concentration divided by urine creatinine value for correction. Immunohistochemical staining was used to do TNF- alpha, IL-6, WT1 renal tissue staining, and analyzed using image analysis software. IBM spss21.0 statistics soft for statistical analysis. 1 general data: (1) compared with the control group, I G AN systolic pressure, diastolic pressure, serum creatinine, uric acid, beta 2- microglobulin, total cholesterol, triglyceride significantly increased, serum albumin, e GFR significantly decreased, the difference was statistically significant (P0.05). The differences in sex, age, and fasting blood glucose in the two groups were not statistically significant (P0.05). (2) comparison between the two groups in the experimental group: Ig AN IV compared with the I~III level patients. The systolic pressure, diastolic pressure, urine protein, serum creatinine, uric acid, beta 2- microglobulin, total cholesterol, triglyceride, serum albumin, e GFR, urinary osmotic pressure decreased significantly (P0.05). There was no significant difference in sex, age, and fasting blood glucose between the two groups (P0.05) the changes of.2 TNF- A: (1) TNF- in the renal tissue. The expression of TNF- alpha was mainly expressed in the cytoplasm of proximal tubular epithelial cells. The atrophy proximal tubules were the most obvious, yellow or brown granules. The average optical density of TNF- alpha in the renal tissue of the I~III grade Ig AN patients was (17.12 + 5.22), IV, and the average optical density of TNF- a in the renal tissue of V grade Ig AN was (35.15 + 9.42). The difference was statistically significant (P0.05). (2) the level of urinary TNF- alpha in patients with Ig AN was (23.18 + 10.09) ng/mg. Cr, and the level of urine TNF- a in the normal control group was (11.92 + 2.53) ng/mg. Cr, the experimental group was significantly higher than the two, and the difference was statistically significant (P0.05). The level of two groups in the test group was (15.70 + 4.98). The level of urine TNF- alpha in patients with Cr, IV, V Ig AN was (29.95 + 8.49) ng/mg. Cr, the heavier the pathological type, the higher the level of urinary TNF- alpha, the difference was statistically significant (P0.05).3 IL-6: (1) the expression in the renal tissue was mainly expressed in the proximal tubule cell cytoplasm, and the atrophied proximal tubules were most obvious, yellow or brown. The average optical density of IL-6 in renal tissue of I~III class Ig AN patients was (24.25 + 11.98), and the average optical density of IL-6 in renal tissue of IV and V grade Ig AN patients was (52.57 + 20.15), the difference was statistically significant (P0.05). (2) the level of urinary tract of Ig AN patients was (20.45 + 10.34), and the level of urine samples in normal control group was 5.. 90 + 2.31) pg/mg. Cr, compared with the two, the experimental group was significantly higher, and the difference was statistically significant (P0.05). The level of urinary IL-6 in the two groups of the experimental group was (13.18 + 5.30) ng/mg. Cr, IV, V class Ig. The higher the pathological type, the higher the level of urinary tract, the difference was statistically significant. 05) the expression of WT1 in.4 renal tissue: WT1 was mainly expressed in the nucleus of normal poddal and yellow or brown yellow granules. The average optical density of WT1 in the renal tissue of the I~III class Ig AN patients was (14.15 + 5.30), IV and V Ig AN were (9.44 + 3.51), and the difference was statistically significant. The results of the correlation analysis: (1) the correlation analysis of TNF- a in renal tissue: the expression of TNF- alpha in renal tissue of patients with Ig AN and systolic pressure, diastolic pressure, urinary protein, serum creatinine, uric acid, beta 2- microglobulin, total cholesterol, triglyceride, mesangial hyperplasia, glomerulosclerosis, interstitial fibrosis, renal tubule atrophy, IL-6 positive expression, urinary TNF- a, urinary IL-6 Positive correlation was negative correlation with serum albumin, e GFR, urine osmotic pressure and WT1 positive expression, and no significant correlation with age and fasting blood glucose. (2) urinary TNF- alpha was associated with various indexes: the level of urinary TNF- A and systolic pressure, diastolic pressure, urinary protein, serum creatinine, uric acid, beta 2- microglobulin, total cholesterol, mesangial hyperplasia, glomerulosclerosis Interstitial fibrosis, renal tubule atrophy, positive expression of TNF- alpha, positive rate of IL-6, positive correlation of urinary IL-6, negative correlation with serum albumin, e GFR, urinary osmotic pressure, positive expression of W T1, and no significant correlation with age, fasting blood glucose and triglyceride. (3) the correlation of IL-6 in renal tissue with each index: the IL-6 expression and collection in the renal tissue of Ig AN patients Contraction pressure, diastolic pressure, urine protein, serum creatinine, uric acid, beta 2- microglobulin, total cholesterol, mesangial hyperplasia, glomerulosclerosis, interstitial fibrosis, renal tubule atrophy, TNF- alpha positive expression, urinary TNF- alpha, IL-6 positive correlation, negative correlation with serum albumin, e GFR, urinary osmotic pressure, w T1 positive expression, and age, fasting glycemia, triglyceride free Significant correlation. (4) urine IL-6 and the correlation analysis: IL-6 level and systolic pressure, diastolic pressure, diastolic pressure, urinary protein, creatinine, uric acid, beta 2- microglobulin, total cholesterol, mesangial hyperplasia, glomerulosclerosis, interstitial fibrosis, renal tubule atrophy, TNF- alpha positive expression rate, IL-6 positive expression rate, positive correlation of urinary TNF- a, and serum albumin, e G FR, urinary osmotic pressure and w T1 positive expression have negative correlation with age, fasting blood glucose and triglyceride. Conclusion: 1 TNF- alpha, IL-6 aggravates Ig AN foot cell injury and promotes the progression of.2 urine TNF- alpha. The level of IL-6 is expected to be a reliable index for evaluating the local TNF- alpha and IL-6 metabolism. A noninvasive method of examination.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R692.31

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本文編號：1908276