CKD患者肾组织α-SMA的表达与颈动脉内膜厚度的关系

发布时间：2018-05-13 17:10

本文选题：慢性肾脏病 + α-SMA　；参考：《河北医科大学》2014年硕士论文

【摘要】：目的：慢性肾脏病（Chronic Kidney Disease, CKD）的发病率已经逐年上升，尤其是在发达国家。已经严重影响了人们的生存质量。而CKD最终发展为终末期肾病（End stage renal disease， ESRD）以后需要的维持治疗以及并发症的治疗导致昂贵的医疗费用，终末期肾病对人生存质量也有着巨大的影响。慢性肾脏病是发生心血管事件的高危因素，而心血管事件又是CKD的最主要的死亡原因。有研究表明，心血管并发症占终末期肾病死亡原因的50%。颈动脉内膜增厚是心血管疾病发生的一个窗口，对颈动脉内膜厚度的监测，可以直观的预测心血管事件的发生。正常人肾组织内小动脉中膜有丰富的α-SMA的表达，中膜内膜化是CVD及CKD血管重塑的基本病变，也是CKD发生CVD的基础。而在慢性肾脏病患者动脉中层发生严重钙化时其表达会明显减少。本实验主要研究各期CKD患者肾内小动脉α-SMA的表达程度的差异，肾内小动脉α-SMA的表达程度与颈动脉内膜厚度的关系以及肾间质α-SMA的表达阳性程度与肾间质损伤程度的关系，揭示肾组织α-SMA的表达与肾组织病变程度的关系并通过肾活检时检测肾组织α-SMA的阳性程度来预测心血管事件。方法：选取2012年3月至2012年9月在河北医科大学第二医院住院行肾活检明确肾脏病理改变的患者63例。按照eGFR分为3组，CKD1期病人26例，CKD2期病人21例，CKD3期病人13例，CKD4期病人3例，行肾活检后肾组织用FAA固定液固定，包埋后以2um厚度连续切片，行PAS染色，PASM染色以及免疫组化染色，观察肾间质纤维化程度、肾内小动脉以及肾间质α-SMA的表达程度，应用PAS染色以及PASM染色结果判断肾间质病变程度，连续的观察50个高倍镜视野，观察肾小管腔有无扩张、萎缩、变性，肾间质有无炎性细胞浸润及肾间质纤维化程度，将肾小管病变程度分4级。组化染色在同一时间同一条件下进行。光镜下观察每张标本染色结果，免疫组化结果按照肾小管胞浆以及小动脉壁上出现棕黄色颗粒或块状沉积为阳性结果，并在高倍镜下观察，选取5个阳性结果区域进行图像分析，得出阳性面积以及累积光密度值，计算后得出平均阳性面积百分比以及平均光密度值，以此作为肾组织α-SMA表达阳性程度的定量结果。结果：1肾内小动脉α-SMA的平均光密度：CKD1期组0.2816±0.0161；CKD2期组0.2681±0.0990；CKD3期组0.2172±0.0512，CKD4期组0.1916±0.0301,肾内小动脉α-SMA平均阳性面积百分比：CKD1期组22.2301±6.3452%；CKD2期组19.1032±9.3423%；CKD3期组14.3401±12.3427%，CKD4期组10.4049±11.6902%：各组之间两两比较均有统计学差异(P＜0.05）。 2肾间质α-SMA的平均光密度: CKD1期组0.0231±0.3252；CKD2期组0.1631±0.4962；CKD3期组0.2117±0.5162，CKD4期组0.3016±0.3901.肾间质平均阳性面积百分比: CKD1期组2.9041±1.1002%；CKD2期组4.3079±1.6201%；CKD3期组13.5078±1.2504%，CKD4期组20.3016±0.9061%各组之间两两比较均有统计学差异(P＜0.05） 3颈动脉内膜厚度：CKD1期组患者0.5021±0.0401mm；CKD2期组0.5137±0.1042mm； CKD3期组0.8147±0.1016mm； CKD4期组1.1047±0.1106mm。CKD1期组患者与CKD2期组患者比较IMT变化无统计学意义，CKD1期组与CKD3期组CKD4期组各组之间两两比较均有统计学差异(P＜0.05）。CKD2期组与CKD3期组CKD4期组各组之间两两比较均有统计学差异(P＜0.05）。 4肾内小动脉α-SMA平均阳性面积百分比与肌酐、血压、血钾、cIMT呈负相关关系，与Co2结合力、TG、TC呈正相关关系(P＜0.05）；肾间质平均阳性面积百分比与肌酐、血压、血钾、cIMT呈正相关关系，与Co2结合力、TG、TC呈负相关关系(P＜0.05）结论：肾组织α-SMA的表达的变化可能参与了CKD的发生发展。联合检测肾内小动脉以及肾间质α-SMA的表达程度与颈动脉内膜厚度的关系可为CKD患者发生心血管意外的可能性提供一定的依据。
[Abstract]:Objective: the incidence of Chronic Kidney Disease (CKD) has increased year by year, especially in developed countries. It has seriously affected people's quality of life. And CKD eventually developed for end-stage renal disease (End stage renal disease, ESRD) after the maintenance of treatment and the treatment of complications resulting in expensive medical costs, End-stage renal disease also has a huge impact on the quality of life. Chronic kidney disease is a high risk factor for the occurrence of cardiovascular events and cardiovascular events are the most important cause of death in CKD. Studies have shown that the 50%. carotid artery thickening is a window of cardiovascular disease in the cause of the death of end-stage renal disease. The monitoring of carotid artery intima thickness can directly predict the occurrence of cardiovascular events. The membrane of the small arteries in the normal human renal tissue is rich in the expression of alpha -SMA. Middle membrane intima is the basic lesion of CVD and CKD vascular remodeling and the basis of CVD in the occurrence of CKD. The difference in the expression of alpha -SMA in renal arterioles of CKD patients at various stages, the relationship between the expression of alpha -SMA and the thickness of carotid artery intima as well as the relationship between the expression of the renal interstitial alpha -SMA and the degree of renal interstitial injury, and the expression of the renal tissue alpha -SMA and the degree of renal tissue lesion in the renal tissue were investigated. The cardiovascular events were predicted by detecting the positive level of alpha -SMA in renal tissue by renal biopsy.
Methods: from March 2012 to September 2012, 63 patients with renal pathological changes in the second hospital of Hebei Medical University were selected. According to eGFR, they were divided into 3 groups, 26 cases in stage CKD1, 21 in CKD2 stage, 13 in phase CKD3 and 3 in CKD4 stage. After renal biopsy, the renal tissue was fixed by FAA fixation, and the thickness of 2um was continuous after embedding. Sections, PAS staining, PASM staining and immunohistochemical staining were used to observe the degree of renal interstitial fibrosis, renal arterioles and the expression of renal interstitial alpha -SMA. PAS staining and PASM staining were used to determine the degree of renal interstitial lesions. 50 high magnification fields were observed continuously, and whether the renal tubules were dilated, atrophic, denatured, and renal interstitium were observed. The degree of inflammatory cell infiltration and renal interstitial fibrosis was divided into 4 levels. The histochemical staining was carried out at the same time on the same condition. The results of each specimen were observed under the light microscope. The results of immunohistochemical staining were positive according to the brown yellow particles or lump deposits on the renal tubules and the wall of the arteriole, and under high magnification. The positive area and the cumulative light density value were obtained from 5 positive results regions, and the average positive area percentage and the mean light density were calculated as a quantitative result of the positive degree of the expression of the renal tissue alpha -SMA.
Results: 1 the mean light density of alpha -SMA in the intrarenal arteriole was 0.2816 + 0.0161 in the CKD1 phase group and 0.2681 + 0.0990 in the CKD2 phase group, 0.2172 + 0.0512 in the CKD3 stage and 0.1916 in the CKD4 stage, and the average positive area of the alpha -SMA in the renal arteriole: the CKD1 stage group was 22.2301 + 22.2301, CKD2 phase group 19.1032 + 9.3423%, CKD3 phase group 14.3401 + CKD4, CKD4. The period group was 10.4049 + 11.6902%: there was a significant difference between 22 groups (P < 0.05).
Mean optical density of 2 renal interstitial alpha -SMA: CKD1 phase group 0.0231 + 0.3252, CKD2 stage group 0.1631 + 0.4962, CKD3 stage group 0.2117 + 0.5162, CKD4 stage group 0.3016 + 0.3901. mean renal interstitial mean positive area percentage: CKD1 phase group 2.9041 + 1.1002%, CKD2 phase group 4.3079 + 1.6201%, CKD3 group 13.5078 + 1.2504%, CKD4 period group between each group There were statistical differences between 22 (P < 0.05).
3 carotid artery intima thickness: the CKD1 group was 0.5021 + 0.0401mm, the CKD2 group was 0.5137 + 0.1042mm, the CKD3 group was 0.8147 + 0.1016mm, and the 1.1047 + 0.1106mm.CKD1 phase group in the CKD4 group and the CKD2 group compared with the CKD2 group, and the IMT changes were not statistically significant. There was a statistically significant difference between the CKD1 phase and the CKD3 group. 0.05) there were significant differences between the 22 groups in the.CKD2 group and the CKD3 stage CKD4 group (P < 0.05).
4 the average positive area percentage of alpha -SMA in renal arterioles was negatively correlated with creatinine, blood pressure, blood potassium and cIMT, and positive correlation with Co2 binding force, TG and TC (P < 0.05). The percentage of mean positive area of renal interstitium was positively correlated with creatinine, blood pressure, potassium and cIMT, and negative correlation with Co2 binding force, TG and TC (P < 0.05).
Conclusion: the changes in the expression of the renal tissue alpha -SMA may be involved in the development of CKD. The relationship between the renal arteriole and the expression of the renal interstitial alpha -SMA and the thickness of the carotid artery intima can provide a certain basis for the possibility of cardiovascular accident in the patients with CKD.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692

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