血小板衍生生长因子BB及受体在狼疮性肾炎患者肾小球及球旁器中的表达与临床相关性研究
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摘要
目的：通过免疫组化方法检测50例LN (Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ型)肾活检组织中PDGF-BB及PDGFRβp的表达,研究其表达量与内生肌酐清除率、C3、白蛋白、SLEDAI评分之间的相关性,探讨PDGF-BB及PDGFR-β在肾小球及球旁器中的表达水平及意义。
方法：采用免疫组织化学(SABC)法检测50例狼疮肾炎患者肾活检组织中的PDGF-BB及PDGFR-β表达水平,并结合临床资料进行统计学分析。
结果：
1.LN及对照肾组织免疫组化染色结果表明,PDGF-BB及PDGFR-β在LN肾活检组织中的表达明显高于正常肾组织；
2.LN不同病理类型肾小球及球旁器PDGF-BB及PDGFR-β表达量不同,以Ⅳ型LN为最高,其次为Ⅱ、Ⅲ、Ⅴ及Ⅰ型；
3.增殖型PDGF-BB及PDGFR-β表达量高于非增殖型狼疮性肾炎患者；
4.LN肾小球,球旁器中PDGF-BB及PDGFR-β的表达与内生肌酐清除率、白蛋白具有低度相关性；与狼疮活动指标补体C3, SLEDAI评分具有低度相关性；
5.LN中Ⅳ型PDGF-BB及PDGFR-p的表达较其它四型明显升高,而内生肌酐清除率、补体C3水平明显低于其它型；结论：本研究发现LN肾组织PDGF-BB及PDGFR-p表达增多,在肾小球,球旁器中的表达均增高,且表达量与肾功能损伤程度及与狼疮活动程度成正相关,PDGF-BB及PDGFR-p在活动性Ⅳ型狼疮肾组织中的表达最多。据此可推测,PDGF-BB及PDGFR-β在LN的细胞增生和炎性浸润过程中发挥重要作用,可能是造成不同LN病理类型的中间因素之一；PDGF-BB及PDGFR-β在狼疮肾炎的发生发展及肾损伤进入纤维化阶段及终末期阶段起重要作用。
Objective
To observe the expression of PDGF-BB and PDGFR-βin renal tissue of 50 patients with lupus nephritis including LN type(Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ) and the relationship of with clinical manifestation, including the clearance of endogenous creatine、Complement3、albumin、SLEDAI. To investigate the expression levels of platelet derived growth factor-BB(PDGF-BB) and PDGFR-βand its level in the glomerular and juxtaglomerular apparatus of patients with lupus Nephritis.
Methods:
The expression of PDGF and PDGFR in renal biopsy specimens of the patients with LN were detected by immunohistochemical stains. We also investigated the relationship between the expression of PDGF-BB and PDGFR in renal tissue in LN and clinical datus.
Result:
1.The positive expressions of PDGF-BB and PDGFR in LN was upregulated significantly when compared to normal controls.
2.Glomerular and Juxtaglomerular apparatus PDGF-BB and PDGFR expresion were different among different pathological type of LN,and the highest was found in type IV LN. than were the typeⅡ、Ⅲ、ⅤandⅠ.
3. The expression of PDGF-BB and PDGFR in proliferated LN was higher than those in the non-proliferated LN.
4.In LN, The expression of PDGF-BB and PDGFR in glomerular and juxtaglomerular apparatus were lower correlation with clearance of endogenous creatinine、albumin、C3 and SLEDAI.
5.Compared with other types LN, InⅣLN, The expression of PDGF-BB and PDGFR-P were higher significantly; clearance of endogenous creatinine、complement3 was lower than others.
Conclusions
Our reseach indicate that in renal tissue the expression of PDGF-BB and PDGFR-P in glomerular and juxtaglomerular apparatus were higher compared with the normal control. In LN, the expressionof PDGF-BB and PDGFR-P in renal tissue was correlated with the condition of renal function. The higher expression of PDGF-BB and PDGFR-β, the more serious damage of the renal function, and it also correlated with the degree of SLE activity. Especially, the expression of PDGF-BB and PDGFR-P was higher in typeⅣLN than the other types. In conclusion, PDGF-BB and PDGFR-βmay participate in glomerular cells and juxtaglomerular apparatus cells proliferation and inflammatory cells infiltration in LN, and may be on factor in the different pathological type formation of LN. PDGF-BB and PDGFR-βplay a very important role in the progression of the end-staged and fibrosis in LN.
方法：采用免疫组织化学(SABC)法检测50例狼疮肾炎患者肾活检组织中的PDGF-BB及PDGFR-β表达水平,并结合临床资料进行统计学分析。
结果：
1.LN及对照肾组织免疫组化染色结果表明,PDGF-BB及PDGFR-β在LN肾活检组织中的表达明显高于正常肾组织；
2.LN不同病理类型肾小球及球旁器PDGF-BB及PDGFR-β表达量不同,以Ⅳ型LN为最高,其次为Ⅱ、Ⅲ、Ⅴ及Ⅰ型；
3.增殖型PDGF-BB及PDGFR-β表达量高于非增殖型狼疮性肾炎患者；
4.LN肾小球,球旁器中PDGF-BB及PDGFR-β的表达与内生肌酐清除率、白蛋白具有低度相关性；与狼疮活动指标补体C3, SLEDAI评分具有低度相关性；
5.LN中Ⅳ型PDGF-BB及PDGFR-p的表达较其它四型明显升高,而内生肌酐清除率、补体C3水平明显低于其它型；结论：本研究发现LN肾组织PDGF-BB及PDGFR-p表达增多,在肾小球,球旁器中的表达均增高,且表达量与肾功能损伤程度及与狼疮活动程度成正相关,PDGF-BB及PDGFR-p在活动性Ⅳ型狼疮肾组织中的表达最多。据此可推测,PDGF-BB及PDGFR-β在LN的细胞增生和炎性浸润过程中发挥重要作用,可能是造成不同LN病理类型的中间因素之一；PDGF-BB及PDGFR-β在狼疮肾炎的发生发展及肾损伤进入纤维化阶段及终末期阶段起重要作用。
Objective
To observe the expression of PDGF-BB and PDGFR-βin renal tissue of 50 patients with lupus nephritis including LN type(Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ) and the relationship of with clinical manifestation, including the clearance of endogenous creatine、Complement3、albumin、SLEDAI. To investigate the expression levels of platelet derived growth factor-BB(PDGF-BB) and PDGFR-βand its level in the glomerular and juxtaglomerular apparatus of patients with lupus Nephritis.
Methods:
The expression of PDGF and PDGFR in renal biopsy specimens of the patients with LN were detected by immunohistochemical stains. We also investigated the relationship between the expression of PDGF-BB and PDGFR in renal tissue in LN and clinical datus.
Result:
1.The positive expressions of PDGF-BB and PDGFR in LN was upregulated significantly when compared to normal controls.
2.Glomerular and Juxtaglomerular apparatus PDGF-BB and PDGFR expresion were different among different pathological type of LN,and the highest was found in type IV LN. than were the typeⅡ、Ⅲ、ⅤandⅠ.
3. The expression of PDGF-BB and PDGFR in proliferated LN was higher than those in the non-proliferated LN.
4.In LN, The expression of PDGF-BB and PDGFR in glomerular and juxtaglomerular apparatus were lower correlation with clearance of endogenous creatinine、albumin、C3 and SLEDAI.
5.Compared with other types LN, InⅣLN, The expression of PDGF-BB and PDGFR-P were higher significantly; clearance of endogenous creatinine、complement3 was lower than others.
Conclusions
Our reseach indicate that in renal tissue the expression of PDGF-BB and PDGFR-P in glomerular and juxtaglomerular apparatus were higher compared with the normal control. In LN, the expressionof PDGF-BB and PDGFR-P in renal tissue was correlated with the condition of renal function. The higher expression of PDGF-BB and PDGFR-β, the more serious damage of the renal function, and it also correlated with the degree of SLE activity. Especially, the expression of PDGF-BB and PDGFR-P was higher in typeⅣLN than the other types. In conclusion, PDGF-BB and PDGFR-βmay participate in glomerular cells and juxtaglomerular apparatus cells proliferation and inflammatory cells infiltration in LN, and may be on factor in the different pathological type formation of LN. PDGF-BB and PDGFR-βplay a very important role in the progression of the end-staged and fibrosis in LN.
引文
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[2]Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus [J].Arthritis Rhem,1982,25(11):1271-1277.
[3]Futamura A ,Izumino K,Nakagawa Y,et al. Effect of the platelet2derived growth factor antagonist trapidil on mesangial cell proliferation in rats. Nephron,1999,81:428-433.
[4]Masaomi Nangaku.Chronic hypoxia and tubulointertitial injury:a final common pathway to end-stage renal failure J Am Soc Nephrol,2005,17:17-25.
[5]Remuzzi G,Perico N,Macia M,et al. The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease.Kidney Int Suppl.2009 Dec; (99):S57-65.
[6]陈松建,徐锡金,等.血小板衍化生长因子及其受体与疾病关系研究进展.医学综述,Medical Recap itulate,May 2008,Vol.14,No.10.
[7]梁科,廖丽琼,等.血小板源性生长因子在狼疮性肾炎患者肾小球中的表达.中国全科医学2005,7；8(14)1141-1142.
[8]黄群华,孙仁宇.血小板源生长因子受体的研究进展.国外医学生理、病理科学与临床分册1998,18(1)83-85.
[9]Hamada T,Ui2Tei K, Imaki J, et al. Molecular cloning of SCDGF-B, a novel growth factors homologous to SCDGF /PDGF-C/fallotein[J]. Biochem Biophys Res Commun,2001,80 (3):733-737.
[10]Alvarez RH, Kantarjian HM, Cortes JE. Biology of p latelet2derived growth factors and its involvement in disease[J]. Mayo Clin Proc,2006,81 (9):1241-1257.
[11]Claesson-WL. P rogress in Grow th Facto r Research,1994;Vo 13:37-54.
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