P16INK4a在原发性系膜增生性肾小球肾炎的表达及临床意义

摘要

目的 探讨原发性系膜增生性肾小球肾炎活检肾组织(MsPGN)细胞周期素依赖蛋白激酶抑制剂P16INK4a在肾组织的表达及其与固有细胞增生、硬化的关系,结合临床参数分析,为延缓慢性肾脏病进展开辟新的途径.方法 采用非生物素免疫组化二步法检测36例MsPGN患者肾活检组织和6例外伤肾切除石蜡包埋肾组织中肾小球和肾小管间质P16INK4a的表达水平.并结合临床资料进行分析.结果 (1)MsPGN组肾小球和小管间质P16INK4a表达升高,与对照组相比,差异有统计学意义(P<0.01).36例中15例硬化、新月体形成组肾小球上高表达,而非硬化、非新月体形成组肾小球上仅部分表达.组间相比差异有统计学意义(P<0.01),小管间质表达差异无统计学意义(P>0.05).(2)36例 MsPGN组中肾小球 P16INK4a表达与未使用类固醇激素/免疫抑制剂、未使用ACEI/ARB正相关(r=0.774、0.497,P<0.01),BP、Scr水平与P16INK4a呈正相关(r=0.64、0.473,P<0.01).Ccr.TMP与P16INK4a呈负相关(r=-0.487、-0.694,P<0.01),而小管间质表达与临床资料不相关.结论 P16INK4a可能起促进异常增殖的肾固有细胞消退作用,并诱导肾脏衰老导致肾小球硬化、新月体形成;P16INK4a表达不仅反映肾功能损伤程度,也间接反映BP和蛋白尿水平;药物干预可影响P16INK4a的表达.%Objective The abnormal proliferation of renal cells underlies the pathology of progressive glomerulosclerosis.Cell proliferation is regulated by cell regulatory proteins.This study aims to investigate the expression of cyclin-dependent kinase inhibitor P16INK4a in renal tissue of patients with primary mesangial proliferative glomemlonephritis(MsPGN)and its clinical significance.Methods Paraffinembedded renal biopsy renal tissue sections from 36 patients with MsPGN were detected by immunohistochemical staining.Normal renal ti8.Sue sections from 6 nephrectomized patients with trauma were used as controls.Possible correlation between p16 positive area and sclerotic and crescentic glomeruli,blood pressure,serum creatinine,endogenous creatinine clearance rate,and total proteinuria were evaluated.Resuits There were very few expression of P16INK4a in normal glomemli and renal tubular-interstitial.Compared to the normal comrol group,the expression of P16INK4a in 36 renal biopsy specimens with MsPG'N was significantly higher(P<0.01),especially in sclerotic and crescentic glomeruli,and it had wild expression of the same components in no sclerotic and crescentic glomeruli.There was a statistic difference(P<0.01).No statistic difference was found between the expression of P16 INK4a in renal tubular-interstitial of two groups(P>0.05).Therewag positive correlation among P16 INK4a of glomeruli without use of glucocorticoid/immunoinlfibitors and ACEI/ARB(r=0.774,0.497,P<0.01),also blood pressure and 8ul～m creatinine(r=0.64,0.473,P<0.01).It was negstively correlated with endogenous creatinine clearance rate and total proteinuria(r=-0.487,-0.694,P<0.01).There is no correlation between P16INK4s and clinical data in renal tubular-interstitial.Conclusion This study demonstrated that overexpression of P16INK4a in renal tissue with MsPGN may promote the regression ofabnormal proliferation and senescence cells,and induce sclerotic and crescentic glomeruli.The expression level of P16 INK4a not only reflected the degree of renal function,but also hypertension and proteinuria.In brief,expression of P16INK4a may be an important marker in renal sclerotic or crescentic glomeruli of MsPGN.Some drugs may prevent the expression of P16INKa.